Latent Disease Research Articles

Outcomes of latent rheumatic heart disease: External validation of a simplified score in patients with and without secondary prophylaxis

BackgroundSecondary antibiotic prophylaxis reduces progression of latent rheumatic heart disease (RHD) but not all children benefit. Improved risk stratification could refine recommendations following positive screening. We aimed to evaluate the performance of a previously developed echocardiographic risk score to predict mid-term outcomes among children with latent RHD. MethodsWe included children who completed the GOAL, a randomized trial of secondary antibiotic prophylaxis among children with latent RHD in Uganda. Outcomes were determined by a 4-member adjudication panel. We applied the point-based score, consisting of 5 variables (mitral valve (MV) anterior leaflet thickening (3 points), MV excessive leaflet tip motion (3 points), MV regurgitation jet length ≥ 2 cm (6 points), aortic valve focal thickening (4 points) and any aortic regurgitation (5 points)), to panel results. Unfavorable outcome was defined as progression of diagnostic category (borderline to definite, mild definite to moderate/severe definite), worsening valve involvement or remaining with mild definite RHD. Results799 patients (625 borderline and 174 definite RHD) were included, with median follow-up of 24 months. At total 116 patients (14.5%) had unfavorable outcome per study criteria, 57.8% not under prophylaxis. The score was strongly associated with unfavorable outcome (HR = 1.26, 95% CI 1.16–1.37, p < 0.001). Unfavorable outcome rates in low (≤6 points), intermediate (7–9 points) and high-risk (≥10 points) children at follow-up were 11.8%, 30.4%, and 42.2%, (p < 0.001) respectively (C-statistic = 0.64 (95% CI 0.59–0.69)). ConclusionsThe simple risk score provided an accurate prediction of RHD status at 2-years, showing a good performance in a population with milder RHD phenotypes.

Tuberculosis reactivation demonstrated by choroiditis and inflammatory choroidal neovascular membrane in a patient treated with immune checkpoint inhibitors for malignant mucosal melanoma

PurposeTo describe a complex case of ocular tuberculosis reactivation with anterior uveitis, choroiditis and inflammatory choroidal neovascular membrane (CNVM) following immune checkpoint inhibitor (ICPI) treatment of malignant mucosal melanoma.MethodsA retrospective collection of medical history, clinical findings and multimodal imaging with literature review of the topic was conducted.ResultsA 52-year-old Romanian female developed reduced vision and photophobia after three cycles of ICPI therapy comprised of ipilimumab and nivolumab. Bilateral anterior uveitis, multiple left eye choroidal lesions and a CNVM were confirmed using slit-lamp examination with ancillary multimodal imaging. Retinal changes in the right eye as well as a history of previously treated posterior uveitis and high-risk ethnicity increased clinical suspicion for ocular tuberculosis (TB) reactivation. The diagnosis was confirmed by TB positivity on polymerase chain reaction (PCR) analysis of lung aspirate followed by significant clinical improvement on systemic anti-tubercular therapy (ATT), systemic steroids and anti-vascular endothelial growth factor (VEGF) therapy.ConclusionsICPIs can cause a myriad of ocular issues, both by primary immunomodulatory effects as well as secondary reactivation of latent disease.

Tuberculosis in Ukrainian War Refugees and Migrants in the Czech Republic and Slovakia: A Molecular Epidemiological Study.

The war in Ukraine has led to significant migration to neighboring countries, raising public health concerns. Notable tuberculosis (TB) incidence rates in Ukraine emphasize the immediate requirement to prioritize approaches that interrupt the spread and prevent new infections. We conducted a prospective genomic surveillance study to assess migration's impact on TB epidemiology in the Czech Republic and Slovakia. Mycobacterium tuberculosis isolates from Ukrainian war refugees and migrants, collected from September 2021 to December 2022 were analyzed alongside 1574 isolates obtained from Ukraine, the Czech Republic, and Slovakia. Our study revealed alarming results, with historically the highest number of Ukrainian tuberculosis patients detected in the host countries. The increasing number of cases of multidrug-resistant TB, significantly linked with Beijing lineage 2.2.1 (p < 0.0001), also presents substantial obstacles to control endeavors. The genomic analysis identified the three highly related genomic clusters, indicating the recent TB transmission among migrant populations. The largest clusters comprised war refugees diagnosed in the Czech Republic, TB patients from various regions of Ukraine, and incarcerated individuals diagnosed with pulmonary TB specialized facility in the Kharkiv region, Ukraine, pointing to a national transmission sequence that has persisted for over 14years. The data showed that most infections were likely the result of reactivation of latent disease or exposure to TB before migration rather than recent transmission occurring within the host country. However, close monitoring, appropriate treatment, careful surveillance, and social support are crucial in mitigating future risks, though there is currently no evidence of local transmission in EU countries.

Detection and management of latent rheumatic heart disease: a narrative review

Rheumatic heart disease (RHD) is a public health concern in many developing nations around the world. Early detection of latent or subclinical RHD can help in reversing mild lesions, retarding disease progression, reducing morbidity and mortality, and improving the quality of life of patients. Echocardiography is the gold-standard method for screening and confirming latent RHD cases. The rates and determinants of progression of latent RHD cases as assessed by echocardiography have been found to be variable through studies. Even though latent RHD has a slow rate of progression, the rate of progression of its subtype, ʻdefiniteʼ RHD, is substantial. A brief training of nonexpert operators on the use of handheld echocardiography with a simplified protocol is an important strategy to scale up the screening program to detect latent cases. Newer advancements in screening, such as deep-learning digital stethoscopes and telehealth services, have provided an opportunity to expand screening programs even in resource-constrained settings. Newer studies have established the efficacy and safety profile of secondary antibiotic prophylaxis in latent RHD. The concerned authorities in endemic regions of the world should work on improving the availability and accessibility of antibiotic prophylaxis.

The absurdity of the latent disease model in mental health: 10,130,814 ways to have a DSM-5-TR psychological disorder

Background Latent disease classification is currently the accepted approach to mental illness diagnosis. In the United States, this takes the form of the Diagnostic and Statistical Manual of Mental Disorders-5-Text Revision (DSM-5-TR). Latent disease classification has been criticized for reliability and validity problems, particularly regarding diagnostic heterogeneity. No authors have calculated the scope of the heterogeneity problem of the entire DSM-5-TR. Aims We addressed this issue by calculating the unique diagnostic profiles that exist for every DSM-5-TR diagnosis. Methods We did this by applying formulas previously used in smaller heterogeneity analyses to all diagnoses within the DSM-5-TR. Results We found that there are 10,130,814 ways to be diagnosed with a mental illness using DSM-5-TR criteria. When specifiers are considered, this number balloons to over 161 septillion unique diagnostic presentations (driven mainly by bipolar II disorder). Additionally, there are 1,951,065 ways to present with psychiatric symptoms, yet not meet diagnostic criteria. Conclusions Latent disease classification leads to considerable heterogeneity in possible presentations. We provide examples of how latent disease classification harms research and treatment programs. We echo recommendations for the dismissal of latent disease classification as a mental illness diagnostic program.

A probabilistic generative model to discover the treatments of coexisting diseases with missing data

Background and ObjectiveComorbidities, defined as the presence of co-existing diseases, progress through complex temporal patterns among patients. Learning such dynamics from electronic health records is crucial for understanding the coevolution of diseases. In general, medical records are represented through temporal sequences of clinical variables together with their diagnosis. However, we consider the specific problem where most of the diagnoses are missing. We present a novel probabilistic generative model with a three-fold objective: (i) identify and segment the medical history of patients into treatments associated with comorbidities; (ii) learn the model associated with each identified disease treatment; and (iii) discover subtypes of patients with similar coevolution of comorbidities. MethodsTo this end, the model considers a latent structure for the sequences, where patients are modeled by a latent class defined by the evolution of their comorbidities, and each observed medical event of their clinical history is associated with a latent disease. The learning process is performed using an Expectation-Maximization algorithm that considers the exponential number of configurations of the latent variables and is efficiently solved with dynamic programming. ResultsThe evaluation of the method is carried out both on synthetic and real world data: the experiments on synthetic data show that the learning procedure allows the generative model underlying the data to be recovered; the experiments on real medical data show accurate results in the segmentation of sequences into different treatments, subtyping of patients and diagnosis imputation. ConclusionWe present an interpretable generative model that handles the incompleteness of EHRs and describes the different joint evolution of coexisting diseases depending on the active comorbidities of the patient at each moment.

Abstract 14701: Agreement Between Handheld and Standard Echocardiography for Diagnosis of Latent Rheumatic Heart Disease in Brazilian Schoolchildren From High-Prevalence Settings

Background: Handheld echocardiography (echo) is the tool of choice for Rheumatic Heart Disease (RHD) screening, based on the 2012 World Heart Federation (WHF) Criteria. We aimed to assess the agreement between screening and standard echo for diagnosis of latent RHD in schoolchildren from an endemic setting. Methods: Over 14 months, 3 non-physicians used handheld machines (GE, VSCAN) and the 2012 WHF Criteria to determine RHD prevalence in low-income public schools in Minas Gerais, Southeast Brazil. Consented children were eligible for participation. Studies were interpreted remotely using a telemedicine cloud-server by 2 experts in Brazil and the US. RHD-positive children (borderline and definite) and those with congenital heart disease (CHD) were referred for standard echo with portable devices (GE, Vivid IQ), with acquisition and interpretation by an expert cardiologist. Agreement between screening and standard echo, by category and according to the WHD criteria, was assessed, and the kappa statistic was applied. Results: A total of 1,390 students were screened in 6 schools and, among these, 110 (7.9%, 95% CI 6.5 - 9.5) were screen-positive and referred for standard echo, with mean age of 14±2 years, 80 (72%) women. Among the 16 cases initially diagnosed as definite RHD, 11 (69%) were confirmed, 4 (25%) reclassified to borderline and 1 to normal. Among the 79 cases flagged as borderline RHD, 19 (24%) were confirmed, 50 (63%) reclassified to normal, 8 (10%) to definite RHD and 2 had mild CHD. Among 11 children with CHD in screening, 4 were confirmed, 5 were reclassified to normal and 2 to RHD. Considering the 4 diagnostic categories, kappa was 0.18. In patients with borderline RHD reclassified to non-RHD, the most frequent WHF criteria was B (isolated mitral regurgitation): 64%, followed by A (2 morphological features of the mitral valve): 31%. In the only patient with definite RHD reclassified to normal, WHF criteria was D (borderline RHD in aortic and mitral valves). After standard echo, RHD prevalence was 3.2% (95% CI 2.3 - 4.2). Conclusions: Although practical, RHD screening with handheld devices tend to overestimate prevalence. Even in endemic settings, continuous education for detection, and application of risk stratification for management are crucial.

Screening for latent infectious disease in patients with alopecia areata before initiating JAK inhibitors therapy: a single-center real-world retrospective study.

Although there is growing evidence supporting the effectiveness of Janus kinase (JAK) inhibitors in treating alopecia areata, the high rate of recurrence following drug discontinuation has led to prolonged treatment courses and raised concerns about long-term safety. In clinical practice, caution should be exercised while using JAK inhibitors for various indications, and a comprehensive pre-treatment screening. This study presents an analysis of screening data collected from real-world settings before the initiation of Janus kinase inhibitors in patients with alopecia areata. Investigators collected retrospective medical data characterizing patients' screening data. Data on demographic and clinical data, including age, sex, disease duration, severity of alopecia tool scale, history of prior treatment, and treatment regimen were recorded. In this cohort (N = 218), JAK inhibitors were initiated for 163 of 218 (74.8%) alopecia areata patients. The numbers of patients positive for antinuclear antibodies, hepatitis B surface antigen, hepatitis C virus antibodies, human immunodeficiency virus antibody, treponema pallidum hemagglutination assay, and thyroid-stimulating hormone were 32 (32/176), 10(10/218), 0 (0/218), 0 (0/218), 3 (3/218) and 9 (9/176), respectively. The number of patients with T-cell spot positive or imaging of the chest indicating tuberculosis was 37 (37/218). Our data provide additional information on the safety profile of JAK inhibitors in patients with alopecia areata. As such, it is necessary and crucial to screen for JAK inhibitors before it is used, particularly for individuals with a high risk of tuberculosis, hepatitis B, and other infections.

Thyroid Autoimmunity and SARS-CoV-2 Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological culprit of COronaVIrus Disease 19 (COVID-19), can enter the cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which has been found in several tissues including in endocrine organs, such as the ovaries, testes, pancreas, and thyroid. Several thyroid disorders have been associated with SARS-CoV-2 infection [subacute thyroiditis (SAT), thyrotoxicosis, and non-thyroidal illness syndrome (NTIS)] and, in part, they are believed to be secondary to the local virus replication within the gland cells. However, as documented for other viruses, SARS-CoV-2 seems to interfere with several aspects of the immune system, inducing the synthesis of autoantibodies and triggering latent or new onset autoimmune disease (AID), including autoimmune thyroid disease (AITD), such as Hashimoto Thyroiditis (HT) and Graves' disease (GD). Several mechanisms have been hypothesized to explain this induction of autoimmunity by SARS-CoV-2 infection: the immune system hyper-stimulation, the molecular mimicry between the self-antigens of the host and the virus, neutrophils extracellular traps, and finally, the virus induced transcriptional changes in the immune genes; nonetheless, more evidence is needed especially from large, long-term cohort studies involving COVID-19 patients, to establish or reject this pathogenetic relationship.

Disease progression model anchored around clinical diagnosis in longitudinal cohorts: example of Alzheimer’s disease and related dementia

BackgroundAlzheimer’s disease and related dementia (ADRD) are characterized by multiple and progressive anatomo-clinical changes including accumulation of abnormal proteins in the brain, brain atrophy and severe cognitive impairment. Understanding the sequence and timing of these changes is of primary importance to gain insight into the disease natural history and ultimately allow earlier diagnosis. Yet, modeling changes over disease course from cohort data is challenging as the usual timescales (time since inclusion, chronological age) are inappropriate and time-to-clinical diagnosis is available on small subsamples of participants with short follow-up durations prior to diagnosis. One solution to circumvent this challenge is to define the disease time as a latent variable.MethodsWe developed a multivariate mixed model approach that realigns individual trajectories into the latent disease time to describe disease progression. In contrast with the existing literature, our methodology exploits the clinical diagnosis information as a partially observed and approximate reference to guide the estimation of the latent disease time. The model estimation was carried out in the Bayesian Framework using Stan. We applied the methodology to the MEMENTO study, a French multicentric clinic-based cohort of 2186 participants with 5-year intensive follow-up. Repeated measures of 12 ADRD markers stemmed from cerebrospinal fluid (CSF), brain imaging and cognitive tests were analyzed.ResultsThe estimated latent disease time spanned over twenty years before the clinical diagnosis. Considering the profile of a woman aged 70 with a high level of education and APOE4 carrier (the main genetic risk factor for ADRD), CSF markers of tau proteins accumulation preceded markers of brain atrophy by 5 years and cognitive decline by 10 years. However we observed that individual characteristics could substantially modify the sequence and timing of these changes, in particular for CSF level of Abeta _{42}.ConclusionBy leveraging the available clinical diagnosis timing information, our disease progression model does not only realign trajectories into the most homogeneous way. It accounts for the inherent residual inter-individual variability in dementia progression to describe the long-term anatomo-clinical degradations according to the years preceding clinical diagnosis, and to provide clinically meaningful information on the sequence of events.Trial registrationclinicaltrials.gov, NCT01926249. Registered on 16 August 2013.

Exploration of Immune Targets for Type 1 Diabetes and Latent Autoimmune Disease Immunotherapy.

Type 1 diabetes (T1D) is an autoimmune disease that destroys pancreatic beta cells, which produce insulin in the islets of Langerhans. The risk of developing T1D is influenced by environmental factors, genetics, and autoantibodies. Latent autoimmune diabetes in adults (LADA) is a type of T1D that is genetically and phenotypically distinct from classic T1D. This review summarizes the accumulated information on the risk factors for T1D and LADA, and immunotherapy trials that offer insights into potential future combined therapeutic interventions for both T1D and LADA to slow the rate of islet cell loss and preserve beta cell function. Future research should also focus on improving intervention doses, conducting more thorough examinations of intervention responders, and/or combining minimally effective single-target immunotherapies to slow the rate of islet cell loss and preserve beta cell function.

Network analysis applied to post-concussion symptoms in two mild traumatic brain injury samples.

A latent disease explanation cannot exclusively explain post-concussion symptoms after mild traumatic brain injury (mTBI). Network analysis offers an alternative form of explanation for relationships between symptoms. The study aimed to apply network analysis to post-concussion symptoms in two different mTBI cohorts; an acute treatment-seeking sample and a sample 10 years post-mTBI. The treatment-seeking sample (n = 258) were on average 6 weeks post-injury; the 10 year post mTBI sample (n = 193) was derived from a population-based incidence and outcomes study (BIONIC). Network analysis was completed on post-concussion symptoms measured using the Rivermead Post-Concussion Questionnaire. In the treatment-seeking sample, frustration, blurred vision, and concentration difficulties were central to the network. These symptoms remained central in the 10 year post mTBI sample. A Network Comparison Test revealed evidence of a difference in network structure across the two samples (p = 0.045). However, the only symptoms that showed significant differences in strength centrality across samples were irritability and restlessness. The current findings suggest that frustration, blurred vision and concentration difficulties may have an influential role in the experience and maintenance of post-concussion symptoms. The impact of these symptoms may remain stable over time. Targeting and prioritising the management of these symptoms may be beneficial for mTBI rehabilitation.

Parsing altered gray matter morphology of depression using a framework integrating the normative model and non-negative matrix factorization

The high inter-individual heterogeneity in individuals with depression limits neuroimaging studies with case-control approaches to identify promising biomarkers for individualized clinical decision-making. We put forward a framework integrating the normative model and non-negative matrix factorization (NMF) to quantitatively assess altered gray matter morphology in depression from a dimensional perspective. The proposed framework parses altered gray matter morphology into overlapping latent disease factors, and assigns patients distinct factor compositions, thus preserving inter-individual variability. We identified four robust disease factors with distinct clinical symptoms and cognitive processes in depression. In addition, we showed the quantitative relationship between the group-level gray matter morphological differences and disease factors. Furthermore, this framework significantly predicted factor compositions of patients in an independent dataset. The framework provides an approach to resolve neuroanatomical heterogeneity in depression.

Tuberculosis contact-tracing results in childhood: a retrospective study in a tertiary-care children’s hospital in Turkey

ABSTRACT Background Smear-positive adults with tuberculosis are the main source of childhood tuberculosis. The evaluation of children exposed to tuberculosis and determination of the disease stages are the cornerstones of managing childhood tuberculosis. Aim To determine the frequency of tuberculous contact, latent tuberculosis infection and tuberculosis disease in children who were in contact with smear-positive adults. Methods This is a single-centre, retrospective study. The medical records of children exposed to tuberculosis (<18 years old) between 2014 and 2018 were investigated. After diagnosing the index cases, the children were referred to the hospital. To identify the children in contact with adults with tuberculosis, a careful medical history, demographic features and physical examination, tuberculin skin test, postero-anterior and lateral chest radiographs, and, if necessary, chest computed tomography and microbiological tests were undertaken. The children’s final diagnosis, treatment regimens and follow-up were documented. The sensitivity, specificity and positive and negative predictive values, tuberculin skin test and chest radiograph imaging were assessed and compared with computed tomography results. Results A total of 150 paediatric patients were exposed to 88 index cases. These were fathers in 29.3% of cases and mothers in 10% of cases. Of the children, 131 (87.3%) were asymptomatic, and physical examination was normal in all children, apart from one who had respiratory symptoms. The tuberculin skin test results were positive in 60 (43%) patients and chest radiograph was abnormal in 100 (66%) children. Findings were consistent with tuberculosis in 34 (40%) of the 84 patients who underwent computed tomography. Fifty (38.5%) of the remaining children were defined as having been in contact with a case of tuberculosis, 41 (31.5%) had latent tuberculous infection and 39 (30%) had tuberculosis disease. Conclusion Pulmonary tuberculosis is asymptomatic in most children but with meticulous use of computed tomography it can be detected in asymptomatic children who have had close contact with tuberculosis. Abbreviation: AFB: acid-fast bacilli; AUC: area under the curve; BCG: bacillus Calmette-Guérin; CI: confidence interval; CT: computed tomography; CXR: chest radiograph; HIV: human immunodeficiency virus; ICD-10: International Classification of Diseases 10; LTBI: latent tuberculosis infection; MDR-TB: multi-drug-resistant tuberculosis; NPV: negative predictive value; PCR: polymerase chain reaction; PPV: positive predictive value; ROC: receiver operating characteristics; SD: standard deviation; TB: tuberculosis; TST: tuberculin skin test; XDR-TB: extensively drug-resistant tuberculosis.

Adenovirus Infection in a Kidney–Pancreatic Transplant Recipient: Case Report

Adenovirus infection in transplant recipients may present from asymptomatic viremia to multisystemic involvement. Most frequently, it occurs in the first year after a kidney transplant, and it is secondary to the reactivation of latent disease. However, primary infection may occur, and disseminated disease is more common when related to primary infection. Kidney involvement may be confirmed by biopsy, although diagnosis may be presumptive. Reduction of immunosuppression and supportive care are important components of therapy. CASE DESCRIPTION: A 41-year-old female renal-pancreatic recipient 12 years before with chronic renal graft dysfunction and a functional pancreatic graft had a history of cytomegalovirus and polyoma virus infection 2 years after transplantation. She was taking tacrolimus, mycophenolate mofetil, and prednisolone. The patient was admitted after persistent uncharacteristic diarrhea 3 weeks before hospitalization without any relevant epidemiologic context. She was dehydrated, and the lab results showed worsened kidney function and leucocytosis. The viral culture revealed adenovirus. Vigorous hydration was implemented, and the mycophenolate mofetil dose was reduced. The patient was discharged, and renal function returned to previous values. DISCUSSION AND CONCLUSION: Adenovirus infection has a wide clinical presentation, and multisystemic involvement may occur in transplant recipients. Supportive care is paramount. The clinical features and viral culture confirm the diagnosis, although tissue samples and quantitative polymerase chain reaction may be required in more severe cases.

Medical image processing using graph convolutional networks: A review

Deep learning, especially graph convolutional networks (GCNs), has been widely applied in various scenarios. Particularly in the field of medical image processing, the research on GCNs have continued to make breakthroughs and has been successfully applied to various tasks, such as medical image segmentation, as well as disease detection, localization, classification and diagnosis. GCNs have demonstrated the capacity to autonomously learn latent disease features from vast medical image datasets. Their potential value and enhanced capabilities in prediction, analysis, and decision-making in perioperative medical imaging have become evident. In recent years, GCNs have rapidly emerged as a research focus in the realm of medical image analysis. First, this review provides a concise overview of the development from convolutional neural networks to GCNs, delineating their algorithmic foundations and network structures. Subsequently, the diverse applications of GCNs in perioperative medical image processing are extensively reviewed, including medical image segmentation, image reconstruction, disease prediction, lesion detection and localization, disease classification and diagnosis, and surgical intervention. Finally, this review discusses the prevailing challenges and offers insights into future research directions for the utilization of GCN methods in the medical field.

Markov-modulated marked Poisson processes for modeling disease dynamics based on medical claims data.

We explore Markov-modulated marked Poisson processes (MMMPPs) as a natural framework for modeling patients' disease dynamics over time based on medical claims data. In claims data, observations do not only occur at random points in time but are also informative, that is,driven by unobserved disease levels, as poor health conditions usually lead to more frequent interactions with the health care system. Therefore, we model the observation process as a Markov-modulated Poisson process, where the rate of health care interactions is governed by a continuous-time Markov chain. Its states serve as proxies for the patients' latent disease levels and further determine the distribution of additional data collected at each observation time, the so-called marks. Overall, MMMPPs jointly model observations and their informative time points by comprising two state-dependent processes: the observation process (corresponding to the event times) and the mark process (corresponding to event-specific information), which both depend on the underlying states. The approach is illustrated using claims data from patients diagnosed with chronic obstructive pulmonary disease by modeling their drug use and the interval lengths between consecutive physician consultations. The results indicate that MMMPPs are able to detect distinct patterns of health care utilization related to disease processes and reveal interindividual differences in the state-switching dynamics.

Mapping the neuroanatomical heterogeneity of OCD using a framework integrating normative model and non-negative matrix factorization.

Obsessive-compulsive disorder (OCD) is a spectrum disorder with high interindividual heterogeneity. We propose a comprehensible framework integrating normative model and non-negative matrix factorization (NMF) to quantitatively estimate the neuroanatomical heterogeneity of OCD from a dimensional perspective. T1-weighted magnetic resonance images of 98 first-episode untreated patients with OCD and matched healthy controls (HCs, n = 130) were acquired. We derived individualized differences in gray matter morphometry using normative model and parsed them into latent disease factors using NMF. Four robust disease factors were identified. Each patient expressed multiple factors and exhibited a unique factor composition. Factor compositions of patients were significantly correlated with severity of symptom, age of onset, illness duration, and exhibited sex differences, capturing sources of clinical heterogeneity. In addition, the group-level morphological differences obtained with two-sample t test could be quantitatively derived from the identified disease factors, reconciling the group-level and subject-level findings in neuroimaging studies. Finally, we uncovered two distinct subtypes with opposite morphological differences compared with HCs from factor compositions. Our findings suggest that morphological differences of individuals with OCD are the unique combination of distinct neuroanatomical patterns. The proposed framework quantitatively estimating neuroanatomical heterogeneity paves the way for precision medicine in OCD.

Shedding Light on Latent Pulmonary Vascular Disease in Heart Failure With Preserved Ejection Fraction

BackgroundAmong patients with heart failure with preserved ejection fraction (HFpEF), a distinct hemodynamic phenotype has been recently described, ie, latent pulmonary vascular disease (HFpEF-latentPVD), defined by exercise pulmonary vascular resistance (PVR) >1.74 WU. ObjectivesThis study aims to explore the pathophysiological significance of HFpEF-latentPVD. MethodsThe authors analyzed a cohort of patients who had undergone supine exercise right heart catheterization with cardiac output (CO) measured by direct Fick method, between 2016 and 2021. HFpEF-latentPVD patients were compared with HFpEF control patients. ResultsOut of 86 HFpEF patients, 21% qualified as having HFpEF-latentPVD, 78% of whom had PVR >2 WU at rest. Patients with HFpEF-latentPVD were older, with a higher pretest probability of HFpEF, and more frequently experienced atrial fibrillation and at least moderate tricuspid regurgitation (P < 0.05). PVR trajectories differed between HFpEF-latentPVD patients and HFpEF control patients (Pinteraction = 0.008), slightly increasing in the former and reducing in the latter. HFpEF-latentPVD patients displayed more frequent hemodynamically significant tricuspid regurgitation during exercise (P = 0.002) and had more impaired CO and stroke volume reserve (P < 0.05). Exercise PVR was correlated with mixed venous O2 tension (R2 = 0.33) and stroke volume (R2 = 0.31) in HFpEF-latentPVD patients. The HFpEF-latentPVD patients had had higher dead space ventilation during exercise and higher PaCO2 (P < 0.05), which correlated with resting PVR (R2 = 0.21). Event-free survival was reduced in HFpEF-latentPVD patients (P < 0.05). ConclusionsThe results suggest that when CO is measured by direct Fick, few HFpEF patients have isolated latent PVD (ie, normal PVR at rest, becoming abnormal during exercise). HFpEF-latentPVD patients present with CO limitation to exercise, associated with dynamic tricuspid regurgitation, altered ventilatory control, and pulmonary vascular hyperreactivity, portending a poor prognosis.

Клінічний досвід застосування стандартизованого національного протоколу УЗД легень у дітей для скринінгових обстежень в амбулаторних умовах та умовах відділень інтенсивної терапії

The article highlights the use of ultrasound diagnostics (US) of the lungs for screening examination of paediatric patients, as it allows for a quick differential diagnosis, a comprehensive assessment of the course of the disease, especially in doubtful cases, a reduction in the time required for examination of patients, and timely adjustment of treatment. Screening ultrasound, combined with physical examination methods, is a kind of «sonographic stethoscope», the use of which simplifies, shortens and improves the diagnostic process and the choice of treatment tactics. Purpose - to prove the feasibility of using a standardised lung ultrasound protocol for screening paediatric patients with symptoms of respiratory system disorders in outpatient and day hospital settings. Materials and methods. The study involved 137 patients aged 4 months to 12 years old. The data of clinical picture, physical and laboratory examinations, computed tomography and lung radiography, semiotics of lung lesions were analysed. For the study, we used stationary ultrasound devices of high and expert class «Samsung» (South Korea), «Mindray» (China), «GE» (USA), which are equipped at the Kinder Clinic, Kyiv, and the National Specialised Children’s Hospital «OKHMATDYT», Kyiv. For paediatric age, a 4-12 mHz linear sensor was mostly used. Results. A total of 137 patients aged 4 months to 12 years were examined. Pneumonia was confirmed in 52 (38%) patients. Of the 137 patients, the polymerase chain reaction test was positive for COVID-19 in 11 (8%) cases and for influenza A in 3 (2.2%) cases. No signs of pneumonia were noted in 85 (62%) children, but 59 (69.4%) of the 85 patients had interstitial syndrome at the B+ and B++ levels, especially expressed in loci I-IV-VII. In the remaining 26 (30.6%) patients, lung ultrasound did not reveal any changes that would indicate disease. They also did not have clear clinical manifestations of acute respiratory viral infection. Separately, we analysed 7 doubtful cases (5.1% of the total) with no or one of the listed diagnostic criteria. Conclusions. This method is recommended for effective lung screening as an «ultrasound stethoscope» for paediatric patients to detect lung pathology, in particular, in the case of latent disease, and to reduce radiation exposure. It is a priority for dynamic monitoring of the course of the disease and the effectiveness of therapeutic tactics. This diagnostic method is affordable and effective for use by doctors of various specialties. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.