Diagnosis Research Articles

Ramming the parasites: Evaluation of quarantine procedures against Haemonchus contortus at sheep markets in Sweden

In Sweden, it is recommended to treat rams at sheep markets with ivermectin and then keep them in quarantine to minimise the risk of transmission of Haemonchus contortus between farms. The aim of this study was to evaluate the effectiveness of this practise. Accordingly the gastrointestinal parasite status of 50 rams purchased at two sheep markets in central Sweden in autumn 2019 was investigated using faecal samples collected on the day of sale (test 1), 12 ± 3 days after ivermectin injection (test 2, in quarantine) and a few months later before inclusion in the new flocks (test 3). We used both traditional diagnostic methods (i.e. identification of nematode eggs in faeces or larvae in cultures when H. contortus eggs could not be identified) and a molecular test based on the digital droplet PCR platform to further identify positive samples. In test 1, conducted in autumn, 40 % of rams were FEC-positive, but only 12 % (six rams) were infected with H. contortus according to conventional routine diagnostics. In test 2, 8 % (four rams) were FEC-positive, including one with 1050 eggs, 90 % of which were identified as H. contortus. This ram was therefore returned to the supplier. However, ivermectin was found to be effective when this animal and a group of lambs from the same farm were treated and tested again. Test 3 was performed on 44 of the same rams (in addition to the returned ram, two rams died in quarantine and the samples from three rams were never provided by the owners). The proportion of FEC-positive animals was 42 %, with an even higher proportion (27 %) of animals being H. contortus-positive than in test 1. The corresponding results for tests 1, 2 and 3 with the ddPCR assay were 18 %, 4 % and 76 %, respectively. This study demonstrates the superiority of DNA detection over microscopy, which is the mainstay in most diagnostic laboratories. Although the combined results confirm that H. contortus survived quarantine in two rams, in the other cases it is not clear whether the spring infection rates are due to re-emergence of persistent larvae from quarantine or reinfection on the new farm. These results suggest not only that we should recommend that sheep farmers use a more sensitive molecular test when purchasing and introducing new animals to their flock, but also that the reliability of injectable ivermectin as a quarantine treatment for removal of adult and larval stages needs further investigation.

Modern approaches and technologies to prevent anastomotic leakage in the gastrointestinal tract

The healing of gastrointestinal anastomoses is acomplex biological process influenced by numerous factors. Various strategies to support healing and prevent anastomotic leakage (AL) exist, encompassing preoperative, intraoperative and postoperative measures. Preoperative interventions aim to optimize the patient and the tissue environment, particularly the gut microbiome. Intraoperative measures are technical in nature and include the choice of surgical access, the anastomotic technique and anastomotic reinforcement. Various procedures of the intraoperative diagnostics enable identification of such anastomoses requiring additional protective measures. Recently, indocyanine green (ICG) fluoroscopy has become established for evaluation of tissue perfusion, while newer techniques such as spectral microscopy offer promising possibilities. Postoperative diagnostic methods aim to identify potential AL as early as possible to enable initiation of therapeutic steps even before the onset of symptoms. These procedures range from various imaging techniques to innovative bioresorbable, pH-sensitive implants for early AL detection. Due to the multifactorial genesis of AL and the diverse technical possibilities, no single method will become established for prevention of AL. Instead, acombination of measures will ultimately lead to optimal anastomotic healing. The use of artificial intelligence and analyses based on the data promises a better interpretation of the vast amount of data and therefore to be able to provide general recommendations.

The Limping Child: A Guide for the Trainees.

Limping is a common presenting complaint in children. Despite this, it remains to be a diagnostic challenge for treating physicians due to an expanded list of etiologies. It arises from a spectrum of disorders, ranging from physiological variations of gait at different stages of development to systemic causes, such as inflammatory diseases or musculoskeletal infections. On rare occasions, non-musculoskeletal causes could result in limping. The diagnostic challenge increases in younger age children where a detailed physical examination that helps identify the exact source of pathology may not be possible. In older patients who have a well-developed gait cycle, the physical assessment might be easier. Clinical assessment in a child presenting with a limp includes gait analysis, which is essential to guide the appropriate request of diagnostic laboratory tests and imaging studies. In this paper, we provide a practical guide for a trainee in General Pediatric and Pediatric Rheumatology on an approach to a limping child, aiming to identify the common causes of limping and to describe normal and abnormal gait cycles. We also discuss other diagnostic considerations in the assessment of these children.

Laboratory Diagnostics for Thrombosis and Hemostasis Testing-Part III.

Laboratory Diagnostics for Thrombosis and Hemostasis Testing-Part III.

Advancing prostate cancer detection: High-accuracy urine test distinguishes between high and low-risk cancers

Prostate cancer remains one of the leading causes of cancer-related deaths among men. The standard method for early detection involves measuring Prostate-specific antigen (PSA) levels in the blood, with elevated PSA levels prompting further diagnostic procedures, such as a prostate biopsy. While effective, biopsies can be painful and carry risks of complications such as fever and urinary tract infections. To reduce unnecessary biopsies, researchers have sought alternative diagnostic methods. In recent years, a urine test was developed for early-stage prostate cancer detection. However, this test struggled to differentiate between aggressive and slow-growing cancers, the latter of which often require minimal treatment and are managed through active surveillance. To address this limitation, scientists at Wunderkind University have significantly enhanced the urine test. By analysing the genomes of thousands of prostate cancer patients, they identified a panel of 16 genes detectable in urine that can effectively distinguish between high-risk and low-risk cancers. When applied to individuals with elevated PSA levels, this improved test demonstrated an impressive 97% accuracy in identifying advanced prostate cancer. This advancement holds great promise for reducing unnecessary biopsies and improving patient outcomes by accurately identifying those needing aggressive treatment versus those suitable for observation. This review paper will explore the development, validation, and clinical implications of this novel urine test, highlighting its potential to transform prostate cancer diagnostics and patient management.

Scalable solutions for global health: the SalivaDirect model

The COVID-19 pandemic caught the world unprepared. Large-scale testing efforts were urgently needed, and diagnostic strategies had to rapidly evolve in response to unprecedented worldwide demand. However, the rollout of diagnostic testing and screening for SARS-CoV-2 was often impeded by logistical challenges, including regulatory delays, workforce shortages, laboratory bottlenecks, and supply chain disruptions. Recognizing these hurdles early on, we developed a testing approach that supported frequent, repeat testing, particularly as communities reopened. We hypothesized and experimentally demonstrated that saliva was a suitable specimen for the detection of SARS-CoV-2. This finding was advanced into the development of open-source, extraction-free reverse transcription polymerase chain reaction protocols using readily available, “off-the-shelf” reagents and equipment for the direct detection of SARS-CoV-2 in saliva (“SalivaDirect’’). Working with the US Food and Drug Administration (FDA), we established a novel regulatory framework wherein the FDA granted Emergency Use Authorization to Yale University to offer the SalivaDirect test protocol to high-complexity diagnostic laboratories (as designated by the Clinical Laboratory Improvement Amendments) with quality oversight provided by Yale. This grew into a network of more than 200 labs across the United States that, as of May 2024, resulted in over 6.5 million SARS-CoV-2 tests. By making the protocol flexible and open-source, laboratories were able to rapidly and economically scale testing using a simple, self-collected saliva specimen. Additionally, fostering a national network of laboratories enabled real-time exchanges, problem solving, and the development of community best practices. Preparing for the next pandemic, or simply the next seasonal epidemic, the SalivaDirect model of deploying a readily available, expandable solution and accompanying network provides a proven method for the successful implementation of pathogen testing in the United States and globally.

Insights into retroperitoneal hemorrhage management: result from a tertiary cardiovascular center prospective cohort

Abstract Background Although rare, retroperitoneal hemorrhage (RPH) during percutaneous cardiovascular interventions is still potentially fatal, poses a critical challenge, often necessitating swift and precise management strategies. Its management is still controversial, and available recommendations are mostly based on expert opinion, and not updated according to recent advancement in the field of interventional cardiology. Purpose To present the rate, clinical characteristics and modern management of patients complicating with RPH in a large tertiary cardiovascular center Method We collected prospectively all consecutive RPH events encountered in the catheterization laboratories of a large tertiary cardiovascular center during 2014-2022. Procedural data from all the diagnostic and therapeutic procedures performed in the same time period, were retrieved from electronic hospital records (EHR). Results Among 89,361 percutaneous cardiovascular diagnostic or therapeutic procedures performed on 69596 patients, 52 (0.058%) episodes (patients) of RPH, (mean age of 56.37±16.84 years with female sex predominance of 36 (69.23%)). Also 2 (3.8%) patients died due to RPH. Non-contrast abdominopelvic CT scan was the most common primary imaging modality for RPH diagnosis, followed by DSA angiography. Of note, 13 (25 %) of patients returned directly to catheterization laboratory for RPH evaluation. Thirty-one (59.6%) patients were ultimately treated conservatively and no patient treated surgically. Structural and peripheral procedures were more prone to RPH. Still a median time of 7.5 hours was needed for RPH diagnosis. Contralateral access was the dominant approach for treating RPH, and although balloon tamponade was used in 11 (52.4 %) patients, 17 (80.9 %) patients were treated ultimately with covered stents; deep femoral and internal iliac arteries were covered in 1 (5.9%) and 2 (11.8%) patients, respectively. Patients treated endovascularly for RPH had higher acute kidney injury and longer hospital stays. Further comprehensive analysis regarding the potential risk factors of RPH are pending. Conclusion Our preliminary analysis from a large tertiary cardiovascular center database, showed RPH is still rare, with acceptable mortality rate of 3.83%. Our data showed the necessity of more precise probability assessment tools to improve the diagnostic time.

Changes in the diagnostic landscape of transthyretin amyloid cardiomyopathy (ATTR-CM): a comparison of tests ordered and test Intervals in 2020 Q4 and 2023 Q4

Abstract Background Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a genetic disease caused when misfolded transthyretin protein is deposited in the myocardium. Amyloidosis driven stiffness in heart muscles results in heart failure symptoms. ATTR-CM is underdiagnosed, requiring specialized tests to identify the condition. Purpose This paper examines and compares diagnostic tests and the time intervals between rounds of testing conducted to identify ATTR-CM in 2020 Q4 and 2023 Q4 in France (FR), Germany (DE), Italy (IT), Spain (ES) and the United Kingdom (UK). Methods A multi-centre online medical chart review was performed between November and December 2020, with 210 (FR: 46, DE: 40, IT: 43, ES: 42, UK: 39) cardiologists/internists providing data on 320 (FR: 71, DE: 63, IT: 64, ES: 63, UK: 59) patients diagnosed with ATTR-CM; and between October and November 2023, with 225 (FR: 45, DE: 48, IT: 48, ES: 45, UK: 39) cardiologists/Internists providing data on 780 (FR: 151, DE: 163, IT: 172, ES: 175, UK: 119) patients. Participants were screened for ATTR-CM patient management. We analysed the diagnostic tests ordered and tracked the intervals between batteries of tests to understand how the timing of diagnosis has changed across the EU4+UK. Results The average number of ATTR-CM diagnostic tests received by reported patients rose from 5.9 in 2020 to 7.4 in 2023, with ECHO with strain imaging (87%), Genetic tests (78%), Cardiac MRI (74%), Laboratory tests (67%), and Scintigraphy tests (65%) as the top 5 tests in Q4 2023. There was a notable increase in the use of ECHO with strain imaging, Laboratory tests, and Scintigraphy tests recorded in the Spanish patient cohort (p<0.01). Reported patients in Italy, Spain & UK received an increased average number of tests (p<0.05) [Table 1]. The recorded interval between the 1st and 2nd test batteries remained consistent between Q4 2020 and Q4 2023 (4.8-4.9 wks.), but the interval between the 2nd to 3rd rounds increased from 4.3 to 5.0 weeks. Timings between batteries increased in the France, Germany, Italy and UK data. Reported patients in Germany continue to experience the shortest intervals between batteries of tests (4.1 wks. between 1st and 2nd; 4.4 wks. between 2nd and 3rd batteries). Between Q4 2020 and Q4 2023, reported patients in Spain had an increase in the average number of tests received from 5.2 to 7.2, and were the only group with decreased time intervals (7.3 to 4.5 wks. between 1st and 2nd; 5.8 to 5.1 wks. between 2nd and 3rd batteries) Conclusion Results indicate that the use of certain diagnostic tests as well as the number of tests used to diagnose ATTR-CM has increased, however, intervals between testing batteries have also increased. This suggests that the increase in the number of tests used to diagnose ATTR-CM is possibly negating the necessity for more frequent testing. Further research in needed to confirm this and assess its impact on early detection of ATTR-CM.Table 1:Diagnostic Procedures by RegionTable 2:Testing battery intervals

Sex differences in RNA transcripts in dilated cardiomyopathy

Abstract Introduction Dilated cardiomyopathy (DCM) is the most common cardiomyopathy and a major cause of heart failure. Differences in clinical presentation and phenotype exist in men and women but the reason for this is not clear. The analysis of the RNA transcripts (mRNA sequencing) offers an opportunity to provide a link between the genome, the proteome, and the phenotype. The aim of this study was to explore sex differences using mRNA sequencing in patients with DCM. Method Our database, an observational prospective cohort study, includes patients referred for suspected cardiomyopathy. The database includes data on patients’ characteristics, symptoms, diagnostic procedures, treatments, cardiac devices, and outcome. Endomyocardial biopsy from the right ventricle was collected and total RNA, including miRNA and other small RNA, was isolated. RNA sequencing and library preparation was performed. Following quality check, reads were aligned to GRCh38 reference genome by STAR (v2.7.10a). Sex-specific differential expression analysis between individuals diagnosed with DCM (cases) versus non-confirmed cardiomyopathy (controls) was performed using DESeq2 (v.1.38.3) adjusting for age, RNA integrity number and systolic blood pressure. After controlling for multiple testing using the Benjamini-Hochberg method, genes with a corrected P-value < 0.05 were considered as being differentially expressed. Gene-set enrichment analysis on differentially expressed genes was performed via Enrichr tool using Descartes cell types and tissues, KEGG biological pathways, DisGeNET, and Gene Ontology Biological Processes (GOBP). Results Patients´characteristics in women and men with DCM is presented in table 1. There was no difference in outcome in men and women (data not shown). Differential expression analyses with transcriptomic data comparing DCM (n=43) versus controls (n=22) stratified by sex (DCM n= 9, (20.9%) women and controls n=7, (30.4%) women) was performed. There was no overlap between differentially expressed genes between sexes (Figure 1). In men gene set enrichment analyses showed that differentially expressed genes were related to pathways involved in dilated and hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (KEGG). Interestingly, these analyses revealed an enrichment of genes related to platelet biology, namely precursors (Descartes), activation (GOBP, KEGG) and platelet disorder (DisGeNET). In women, HLA-DQB1 was more expressed in DCM. HLA-DQB1 is associated with celiac disease, narcolepsy, and type 1 diabetes. Consistently, the enrichment analyses showed an enrichment of genes involved in autoimmune diseases (DisGeNET). Conclusion Women and men with DCM exhibit differently activated RNA transcripts although no difference in phenotype was observed. This may indicate that although DCM can be caused by similar factors in women and men the transcriptome is differently activated which warrants further investigation.Table 1.

Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.

NKX2-1, a crucial transcription factor in thyroid, lung, and brain development, is associated with rare disorders featuring thyroid dysfunction, neurological abnormalities, and respiratory symptoms. The primary challenge in managing NKX2-1-related disorders (NKX2-1-RD) is early diagnosis of the genetic defect and treating specific endocrine disorders. Levothyroxine (LT4) serves as the standard hypothyroidism treatment, with required dosages influenced by the severity of the individual's disorder, which varies widely among affected individuals. This systematic review aims to assess the effectiveness of LT4 treatment in NKX2-1-RD and explore optimal dosing strategies. The primary focus is on the challenges associated with the prompt diagnosis of genetic defects, rather than the established treatment protocols for individual endocrine failures. Adhering to PRISMA guidelines, the review includes 42 studies involving 110 genetically confirmed NKX2-1-RD patients with hypothyroidism. The study investigates congenital hypothyroidism as the most prevalent endocrine alteration, along with gestational and overt hypothyroidism. The administration of LT4 treatment, dosages, and patient responses are analyzed. Among the findings, congenital hypothyroidism emerges as the predominant endocrine alteration in 41% of patients. Notably, LT4 treatment is administered in only 10% of cases, with a mean dose of 52 μg/day. The variability in initiation and dosage is likely influenced by the age at diagnosis. Positive responses, characterized by TSH adjustments within normal ranges, are observed in 11 monitored patients. Early detection of congenital hypothyroidism is emphasized for timely LT4 initiation. Challenges in standardization are highlighted due to the variability in clinical manifestations and diagnostic procedures across NKX2-1-RD cases. While this review provides valuable insights into thyroid and pituitary disease treatment, limited details on LT4 treatment represent a significant study limitation. Key reporting points for future case studies are proposed to enhance the understanding and management of NKX2-1-RD hypothyroidism.

The European Mobile Laboratory: key insights from a decade of outbreak response

Abstract EMLab has responded to emergencies including the West Africa Ebola virus outbreak (2014-2016), the COVID-19 pandemic, and outbreaks of yellow fever, Marburg virus, and Lassa fever. It has deployed mobile labs and experts to many countries, including Guinea, Liberia, Sierra Leone, Nigeria, Uganda, the Democratic Republic of the Congo, Germany, and Greece. With accumulated experience from each deployment, EMLab’s diagnostic expertise has evolved beyond RT-PCR and serological testing to include basic point-of-care tests, haematology, and genomic surveillance capacities, also focusing on interoperability with other response capacities such as EMTs. Critical to mission success, the organization works closely with the WHO and GOARN, and was certified in 2023 as an official German response capacity within the European Civil Protection Pool. The two-year continuous deployment from 2014-2016 was pivotal in shaping EMLab’s evolution, also leading to significant capacity-building efforts in West Africa. In Guinea, for example, a surveillance network of three diagnostic laboratories has been established and successfully detected cases of viral haemorrhagic fevers, including the re-emergence of Ebola virus and the first reported case of Marburg virus in Guinea in 2021. Ultimately, EMLab’s extensive experience demonstrates that effective public health emergency response requires constant evolution, strategic partnerships, and a commitment to building local capacities, paving the way for a more resilient and prepared global health community.

The MorbidGenes panel: a monthly updated list of diagnostically relevant rare disease genes derived from diverse sources.

With exome sequencing now standard, diagnostic labs are in need of a, in principle, to-the-day-accurate list of genes associated with rare diseases. Manual curation efforts are slow and often disease specific, while efforts relying on single sources are too inaccurate and may result in false-positive or false-negative genes. We established the MorbidGenes panel based on a list of publicly available databases: OMIM, PanelApp, SysNDD, ClinVar, HGMD and GenCC. A simple logic allows inclusion of genes that are supported by at least one of these sources, providing a list of all genes with diagnostic relevance. The panel is freely available at https://morbidgenes.uni-leipzig.de and currently includes 5037 genes (as of October 2024) with minimally sufficient evidence on disease causality to classify them as diagnostically relevant. The MorbidGenes panel is an open and comprehensive overview of diagnostically relevant rare disease genes based on a diverse set of resources. The panel is updated monthly to keep up with the ever increasing number of rare disease genes.

Chronic kidney disease in patients with heart failure in German primary care practices: the InspeCKD study

Abstract Background Chronic kidney disease (CKD) is, alongside type 2 diabetes mellitus, the most common comorbidity in patients with heart failure (HF), with a prevalence of 40-50%. HF patients should therefore be screened, monitored, and treated according to international Kidney Disease Improving Global Outcomes (KDIGO) conclusions for early identification and intervention of CKD, with annual determination of eGFR to monitor kidney function and annual urine albumin-to-creatinine ratio (UACR) testing as appropriate. Early diagnosis is important as therapeutic options can be offered to slow the progression of CKD and reduce the risk of cardiovascular complications and mortality. Purpose Currently, there are only limited data available regarding screening, diagnosis and treatment of CKD for HF patients in German primary care physician (PCP) practices. Therefore, this analysis of the InspeCKD study was designed to examine the frequency of use of CKD-specific laboratory diagnostics in HF patients in routine PCP care. Methods In the current data analysis, fully anonymized patient data from German PCP practices were evaluated. In accordance with the screening recommendation of the KDIGO guideline, adult patients with diabetes, hypertension and/or cardiovascular disease, including HF, with at least one year of observation period were included in the analysis. Results The overall patient cohort comprised 448.837 patients from 1.244 German PCP practices. Of the 7.9% HF patients, 6.1% participated in a disease management program (DMP) for coronary heart disease. The average age of HF patients was 74 years. The prevalence of diagnosed CKD in HF patients during the observational period (mean: 1.7 years) was 26.8%. Within the subgroup of patients with HF, serum creatinine to estimate GFR was measured at least once in 48.5% of patients. Urine dipstick testing for albuminuria was performed in 7.4% of patients and UACR was measured at least once in 0.3% of patients. In patients with at least one documented measurement, eGFR and UACR were checked 2.2 and 0.9 times, respectively, per patient and year. Of the HF patients with laboratory-confirmed CKD according to KDIGO criteria, 81.8% were not diagnosed with CKD. Conclusion The analysis shows that, given the high prevalence of CKD in HF patients and the current KDIGO recommendations for early identification and intervention of CKD, a substantial proportion of HF patients in German PCP practices did not receive adequate laboratory diagnostics for early diagnosis of CKD. In addition, the majority of patients with laboratory-confirmed CKD were not diagnosed. Early detection of CKD and the use of evidence-based therapeutic options can significantly reduce the risk of CKD progression. In conclusion, there is an urgent need to raise awareness among PCPs about secondary and tertiary prevention of CKD in patients with HF and to include coordinated CKD screening recommendations in HF guidelines.

Cardiac transthyretin amyloidosis in patients with conduction system disease

Abstract Background/Introduction Cardiac amyloidosis (CA) is characterized by extracellular deposition of misfolded proteins in the heart. The data suggest that cardiac amyloidosis is underappreciated as a cause of common cardiac diseases or syndromes. More than 98% of currently diagnosed cardiac amyloidosis result from fibrils consisting of monoclonal immunoglobulin light chains (AL) or transthyretin (ATTR). The natural history of ATTR cardiomyopathy commonly includes both the conduction system disease and arrhythmias, which may occur years before the onset of heart failure. Conduction abnormalities are commonly encountered among patients with CA and constitute an important cause of morbidity and mortality. Most reports agree that pacemakers are most common in wild type ATTR-CA, followed by hereditary ATTR-CA and, finally, AL-CA. Purpose As unexplained LV wall thickness ≥ 12 mm is a screening sign of possible cardiac ATTR, systematicscreening for CA in patients requiring permanent pacemakers with unexplained LV wall thickness of ≥ 12 mm seems to be rational and could possibly lead to early diagnosis of cardiac ATTR. To the best of our knowledge, the usefulness of such screening has not been investigated before. This project, therefore, aims to determine the prevalence of cardiac ATTR and its subtypes in this preselected group, and to propose the most suitable battery of diagnostic procedures for this purpose. Methods Population to be tested: Consecutive patients ≥50 years referred for permanent pacemaker implantation with unexplained LV wall thickness ≥12 mm determined by echocardiography. The research protocol was that of an open-label prospective study. Biochemistry samples including serum troponin I and NT-proBNP were collected before pacemaker implantation. All patients were screened for ATTR-CA according to the recommendations of the Position statement of the ESC Working group on myocardial and pericardial diseases. Tc-DPD scintigraphy scan served as a gold standard for determining the diagnosis of cardiac ATTR. Results Out of 100 consecutive patients meeting inclusion criteria, 15 % suffered from amyloidosis (12 patients were diagnosed with ATTR and 3 with AL cardiac amyloidosis). Table 1 shows a variety of parameters, many of which differed between patient groups with and without amyloidosis, confirming the wide range of parameters significantly associated with cardiac amyloidosis; our ongoing research in this field could lead to the development of a scoring system for detection of cardiac amyloidosis. Conclusions The prevalence of cardiac amyloidosis in the investigated group was 15 %. Systematic screening for ATTR in patients with unexplained LV wall thickness ≥ 12 mm requiring permanent pacemaker implantation seems to be rational and could possibly lead to an earlier diagnosis of cardiac amyloidosis, especially ATTR.

Children after kidney transplantation show severe cardiac alterations

Abstract Sudden cardiac death is among the most common causes of death in patients with chronic kidney diseases (CKD) after pediatric kidney transplantation (KTx), but defined diagnostic procedures identifying children at risk are not established. Echocardiographically detectable damage in the context of CKD has been described, but there are few data after KTx in childhood. The aim was to characterize structural and functional cardiac alterations on cardiac MRI (cMRI) and echocardiography in children after KTx and to elucidate the significance of diastolic dysfunction in this special context. 46 KTx recipients (mean age 16.0±3.5 years) and due to missing reference values 46 age- and sex-matched healthy controls were examined with non-contrast cMRI. Native T1 time (nT1), left ventricular mass z-score (LVMIz), ejection fraction (EF), global longitudinal strain (GLS) were measured. KTx recipients underwent comprehensive echocardiography: EF, mitral inflow (E-, A-wave), TDI e', E/e'-ratio, isovolumetric relaxation time (IVRT), pulmonary venous flow (PVFsys, PVFdia), atrial reversal (PVF-AR) and left atrial volume index (LAVI), left ventricular mass z-score (LVMz). Multivariable linear regression analysis (co-variates: age, sex, height) were used to show associations between cMRI and echo parameters. In cMRI KTx recipients had a siginficant higher nT1 than healthy controls (septal: 1198±49ms vs. 1155±23ms, p<0.0001; lateral: 1141±57ms vs. 1109±37ms, p=0.003). In KTx recipients, LVMIz was higher (0.1±1.1g/m2 vs. -0.3±0.7g/m2; p=0.026), GLS was lower than in healthy controls (-19± 2.1% vs. -20.3±2.7%, p=0.01). While based on cMRI 2 patients were diagnosed with left ventricluar hypertrophy (LVH), 11% (n=5) displayed LVH on echo. EF was preserved in all patients. However, in echocardiography, 90% (n=40) of the KTx recipients showed diastolic parameters out of the age-specific normal range (Fig.1) with changes in two or more diastolic parameters in half of the cohort. Associations with septal nT1 on cMRI could be demonstrated for septal E/e´ (ß=8.415, p=0.042), A-wave (ß=1.037, p=0.045), LAVI (ß=3.347, p=0.002) and PVF-AR (ß=2.945, p=0.021); associations with lateral nT1: septal E/e´ (ß=9.590, p=0.045) and LAVI (ß=3.393, p=0.009) (Fig. 2); 7 (15 %) had an elevated nT1 septal, lateral and E/e´ out of the normal range. Young KTx recipients show a high prevalence of diastolic dysfunction with preserved EF. Impaired diastolic function was associated with structural alterations reflecting myocardial fibrosis. Our findings suggest that a large number of children after KTx suffer from heart failure with preserved EF – an entity not yet defined in children but described for adults, in whom it is associated with sudden cardiac death. Further studies are needed to describe the clinical relevance of these findings, which gain explicit importance, as the prognosis of HFpEF in adults is improved by SGLT2i, a treatment option not yet considered in our high-risk patient group.

Simulation training for invasive cardiovascular procedures: the Heart-SIMS-1 study

Abstract Introduction Interventional cardiology training has a long learning curve and exposes patients and clinicians to undesirable procedural risks. We aim to assess whether mentored simulation-based training with three dimensional (3D) printed models can improve the procedural skills and safety performance of beginners in coronary diagnostic procedures. Methods Twenty-nine final-year medical students from a single centre were lectured in the basic principles of invasive coronary angiography (ICA) for one-hour, and then randomized to conventional training or simulation training. Conventional training (n=15) consisted in watching a 20-minute video demonstrating all ICA steps in a 3D-printed coronary simulator. Simulation training (n=14) offered the same explanations in a hands-on training session with the 3D-printed model, in pairs, for 20 minutes. The co-primary endpoint was efficacy and safety of performing a simulated ICA in the 3D-printed simulator, installed under sterile drapes, in a conventional angiography suite. Efficacy and safety were graded by a blinded investigator using a pre-specified performance checklist, including the identification of procedural "red flags", graded 0-100%. The secondary endpoint was theoretical knowledge, assessed in a 25-question multiple-choice quiz, graded 0-100%. Results All participants completed the training and evaluation phases. Both elements of the co-primary endpoint were superior in the simulation group: efficacy score of 91.5 ± 3.8 vs 64.6 ± 8.3% and safety score 100.0 (100.0-100.0) vs 62.5 (20.8-79.2) %, p<0.001. The median number of "red flags" were 2 (1-4) in conventional and 0 (0-0) in simulation training recipients (p<0.001). Secondary endpoint was higher in simulation training: 85.7 ± 9.0 vs 76.8 ± 12.7% (p=0.039). Conclusion Mentored simulation-based training of medical students in ICA with 3D-printed models resulted in improved performance regarding efficacy, procedural safety, and theoretical knowledge.ResultsSimulation and evaluation setup

Impact on healthcare costs of adding telemedicine to a multidisciplinary disease management program for heart failure: a sub-analysis of the iCOR trial

Abstract Background Impact of telemedicine on heart failure outcomes has shown conflicting results. Little is known about the effect of these programs on mid-term healthcare costs. Purpose To evaluate the cost-efficacy of a comprehensive telemonitoring program within the vulnerable post-discharge period after an acute heart failure admission. Methods The insuficiència cardiaca Optimizació Remota (iCOR) trial was a single-centre, randomized, open-label study designed to evaluate the efficacy of the addition of telemonitoring and teleintervention to a specialized multidisciplinary nurse-led heart failure (HF) program. Adult patients with a recent hospital admission for acute HF and an acceptable social support and cognitive ability were recruited. This sub-analysis evaluates the effect of telemedicine on mid-term healthcare costs, including clinical events, drugs and devices, technology purchase and maintenance, outpatient care, days of hospitalization, procedures and complementary tests. t-test via bootstrap estimation is used to compare differences between the telemedicine (TM) and the usual care (UC) groups. Results 81 patients were assigned to the TM group and 97 patients to the UC group. Mean age was 74 years, more than 50% had HF with preserved ejection fraction and 25% were frail. Baseline characteristics were well-balanced between groups. Among the TM subgroup, adherence was very high (< 1% of missed biometric daily transmissions). During 6 months of follow-up, mean total healthcare cost per patient was 7949 euros (€) in the UC cohort and 4383 € in the TM cohort (relative risk reduction [RRR] of 45%; between-group differences 3546 €, 95% confidence interval 627-6464 €, bootstrap achieved significance level 0.022). This result was consistent across several subgroups (age, sex, frailty, left ventricular ejection fraction, educational level) and mainly driven by a 63% RRR in costs of hospitalization (which accounted for two-thirds of the total costs) in the TM cohort. 20 patients required HF admissions in the TM group, compared to 51 patients in the TM group (p < 0.001). This was associated with a 59% RRR in the need for diagnostic procedures. Total number of days of hospitalization per patient decreased from 12.2 in the UC group to 4.2 days in the TM group (p = 0.003), impelled by a reduction in HF and cardiovascular days of hospital stay. On the contrary, ambulatory care costs increase two-fold in the TM group compared to UC group. Nevertheless, these costs only accounted for a 19% of the total costs. Cost of devices needed to implement TM supposed 698 € per patient. Use of TM was associated with a 355 € increase in the cost of ambulatory neurohormonal treatment for HF. Conclusions TM implementation during the vulnerable phase after an acute HF admission was associated to a 45% RR reduction in mean total healthcare cost per patient. This result was driven by an almost two-thirds decrease in costs of hospitalization.UC and TM total healthcare costs

Sex-specific syncope characteristics in the early diagnosis of cardiac syncope

Abstract Background The Lancet women and cardiovascular disease commission requested evaluating sex-specific approaches in the diagnosis and management of acute cardiovascular disease. Purpose We aimed to explore 1) the utility of sex-specific syncope characteristics in the early diagnosis of cardiac syncope 2) sex-related differences in the management and outcomes of patients with a cardiac syncope. Methods Thirty-one syncope characteristics were prospectively assessed in women and men presenting with syncope to the emergency department (ED) in an international multicenter study. The final diagnosis of cardiac syncope was centrally adjudicated by two independent cardiologists. Sex-specific differences in the prevalence of syncope characteristics and their positive likelihood ratio (pLR) for cardiac syncope were the primary diagnostic endpoints. Sex-specific differences in hospital admission, diagnostic procedures performed in patients with a cardiac syncope and adverse events in patients directly discharged from the ED during one-year follow-up were secondary endpoints. Results Among 2661 patients (median age 71 years, 1099 women and 1562 men), 14.6% of women and 18.2% of men (p=0.02) were adjudicated to have a cardiac syncope. Eleven syncope characteristics showed diagnostic utility (statistically significant pLRs) in assessing cardiac syncope in the overall population. However, none of the syncope characteristics demonstrated significant sex interaction. Women adjudicated as having a cardiac syncope were as likely to be hospitalized as men (OR 1.12; 95% CI: 0.61-2.08, p=0.7) and to receive telemetry (40% vs 41%, p=0.9), ergometry (3.1% vs 6.3%, p=0.4), a holter (21% vs 17%, p=0.3), a loop recorder (0.6% vs 3.9%, p=0.06) and an echocardiogram (69% vs 65%, p=0.4). Among the 591 women and 796 men directly discharged from the ED, 18 women (3%) and 36 men (5%) were finally adjudicated as cardiac syncope. Noteworthy, within this cardiac syncope subgroup, 28% of women experienced major adverse cardiac events (MACE) during the 365-day follow-up period, in comparison to 67% men (OR 0.20; 95% CI: 0.06-0.68, p=0.011, Figure). Conclusion Syncope characteristics contributed to the early diagnosis of cardiac syncope, however, none had a significant sex interaction. Women with a cardiac syncope had a similar likelihood of being hospitalized and receiving diagnostic testing. Compard to men, women had a significantly decreased risk of MACE when not hospitalized after a cardiac syncope.Kaplan-Meier curves for 1 year MACE

Lipedematous scalp and lipedematous alopecia: a narrative review.

Lipedematous scalp (LS) and lipedematous alopecia (LA) are uncommon conditions with an unclear cause. Over the past century, about 115 cases have been documented in the literature. It is unknown if these disorders are indeed so uncommon or if cases that accept the illness as a structural alteration or are asymptomatic make the disease appear more uncommon than it is. Despite the fact that the majority of cases are seen in young and middle-aged people, the cases involving congenital, elderly, and children have also been reported. In the reported cases, female gender was observed to be dominant. The most significant clinical characteristics include felty swelling of the scalp in both disorders, diffusely or locally enlarged subcutaneous tissue with a swampy, spongy feel, and varied degrees of alopecia in LA. There is still much to learn about the pathogenetic mechanisms and therapeutic approaches for LA and LS. In this article, I review the general clinical characteristics, supposed pathogenetic mechanisms, histopathologic characteristics, diagnostic procedures, and management strategies for LS and LA.

Diagnosis and Management of Malignant Epithelial Nail Unit Tumors

Background: Malignant epithelial nail unit tumors pose significant diagnostic and therapeutic challenges due to their clinical presentation often mimicking benign conditions and due to the need to preserve as much nail unit function as possible during surgery. Early detection is crucial, even if none of these tumors represent a life-threatening disease. Objectives: This review focus on squamous cell carcinoma, verrucous carcinoma, eccrine porocarcinoma, onychocytic carcinoma, basal cell carcinoma, malignant onychopapilloma, malignant onycholemmal cyst and onycholemmal carcinoma. Methods: Existing literature on the aforementioned tumors has been revised and synthesized. Results: Clinical presentation, pathology, diagnostic procedures, risk factors and the challenges associated with surgical management have been described in detail. Conclusions: Malignant epithelial tumors of the nail unit require careful evaluation and management due to their complex presentation. Early detection and an informed surgical approach are essential to improve patient outcomes and minimize complications.