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Mayo Clinic Proceedings. Digital Health Jun 2024This study aimed to review the application of natural language processing (NLP) in thyroid-related conditions and to summarize current challenges and potential future...
This study aimed to review the application of natural language processing (NLP) in thyroid-related conditions and to summarize current challenges and potential future directions. We performed a systematic search of databases for studies describing NLP applications in thyroid conditions published in English between January 1, 2012 and November 4, 2022. In addition, we used a snowballing technique to identify studies missed in the initial search or published after our search timeline until April 1, 2023. For included studies, we extracted the NLP method (eg, rule-based, machine learning, deep learning, or hybrid), NLP application (eg, identification, classification, and automation), thyroid condition (eg, thyroid cancer, thyroid nodule, and functional or autoimmune disease), data source (eg, electronic health records, health forums, medical literature databases, or genomic databases), performance metrics, and stages of development. We identified 24 eligible NLP studies focusing on thyroid-related conditions. Deep learning-based methods were the most common (38%), followed by rule-based (21%), and traditional machine learning (21%) methods. Thyroid nodules (54%) and thyroid cancer (29%) were the primary conditions under investigation. Electronic health records were the dominant data source (17/24, 71%), with imaging reports being the most frequently used (15/17, 88%). There is increasing interest in NLP applications for thyroid-related studies, mostly addressing thyroid nodules and using deep learning-based methodologies with limited external validation. However, none of the reviewed NLP applications have reached clinical practice. Several limitations, including inconsistent clinical documentation and model portability, need to be addressed to promote the evaluation and implementation of NLP applications to support patient care in thyroidology.
PubMed: 38938930
DOI: 10.1016/j.mcpdig.2024.03.007 -
Cureus Jun 2024Autoimmune hepatitis (AIH) is a condition resulting in chronic, inflammatory changes to the liver. Primary biliary cholangitis (PBC) is an autoimmune condition that...
Autoimmune hepatitis (AIH) is a condition resulting in chronic, inflammatory changes to the liver. Primary biliary cholangitis (PBC) is an autoimmune condition that destroys intrahepatic bile ducts. Overlap syndrome with concomitant AIH and PBC comprises a rare subgroup of patients with immune-mediated liver disease, with incidence rates of male patients being exceedingly uncommon in a predominantly female patient population. Our case report investigates a rare case of a 41-year-old male patient diagnosed with overlapping AIH and PBC. He initially presented with symptoms of fatigue, pruritus, and episodes of Raynaud's phenomenon, in addition to findings of persistently elevated liver enzymes despite lifestyle modifications. He had no past medical history, no history of alcohol use disorder, and no family medical history of chronic liver disease. Imaging did not reveal evidence of cirrhosis. Further diagnostic workup was significant for elevated immunologic markers for antinuclear antibodies (ANA) with positive centromere and cytoplasmic patterns, antimitochondrial antibodies (AMA) with F-actin antibodies, anti-smooth muscle antibodies (ASMA), and cytoplasmic antinuclear cytoplasmic antibodies (ANCA C). Liver biopsy showed prominent plasma cells and rare granulomas, consistent with the diagnosis of AIH with a component of PBC, respectively. He was started on ursodeoxycholic acid (UDCA), demonstrating a near-complete clinical response with resolution of symptoms and normalization of liver enzymes. Studies investigating the low incidence of male patients with overlap syndrome are limited, as current research is overwhelmingly based on studies with predominantly female subjects. However, most studies generally recommend treatment with both UDCA and corticosteroids to reduce symptoms and biochemical markers. Our case report highlights a rare case of a male patient documenting excellent biochemical and clinical responses to monotherapy with UDCA. A possible theory is that our patient's early treatment (prior to advanced disease progression) is associated with his near-complete biochemical response and symptomatic resolution on UDCA alone. Further research is needed to fully understand the clinical course and long-term prognosis of male patients with overlap syndrome. Our patient remains in life-long follow-up to monitor if or when he requires treatment with corticosteroids in addition to current monotherapy with UDCA..
PubMed: 38938909
DOI: 10.7759/cureus.63312 -
JACS Au Jun 2024This study highlights the novel potential of molecular aggregates as inhibitors of a disease-related protein. Enzyme inhibitors have been studied and developed as...
This study highlights the novel potential of molecular aggregates as inhibitors of a disease-related protein. Enzyme inhibitors have been studied and developed as molecularly targeted drugs and have been applied for cancer, autoimmune diseases, and infections. In many cases, enzyme inhibitors that are used for therapeutic applications interact directly with enzymes in a molecule-to-molecule manner. We found that the aggregates of a small compound, Mn007, inhibited bovine pancreatic DNase I. Once Mn007 molecules formed aggregates, they exhibited inhibitory effects specific to DNases that require divalent metal ions. A DNase secreted by causes streptococcal toxic shock syndrome (STSS). STSS is a severe infectious disease with a fatality rate exceeding 30% in patients, even in this century. disrupts the human barrier system against microbial infections through the secreted DNase. Until now, the discovery/development of a DNase inhibitor has been challenging. Mn007 aggregates were found to inhibit the DNase secreted by , which led to the successful suppression of growth in human whole blood. To date, molecular aggregation has been outside the scope of drug discovery. The present study suggests that molecular aggregation is a vast area to be explored for drug discovery and development because aggregates of small-molecule compounds can inhibit disease-related enzymes.
PubMed: 38938790
DOI: 10.1021/jacsau.4c00210 -
Neurology. Clinical Practice Jun 2024To study the frequency, causes, and consequences of seizure-related falls and near falls in LGI1-IgG autoimmune encephalitis.
OBJECTIVES
To study the frequency, causes, and consequences of seizure-related falls and near falls in LGI1-IgG autoimmune encephalitis.
METHODS
We retrospectively reviewed 136 patients seen at Mayo Clinic with (1) LGI1-IgG seropositivity, (2) clinical phenotypes compatible with LGI1-IgG autoimmune encephalitis, and (3) falls or near falls related to seizures. The clinical documentation, MRI, and EEG data were collected and reviewed.
RESULTS
In this cohort of 136 patients, 27% (n = 36) had falls or near falls related to seizures. The median age was 67 years (range 49-86 years) and 23/36 (64%) were male. Facio-brachio-crural dystonic seizures (21/36, 58%) and drop attacks (9/36, 25%) were the most common causes. Seizure-related falls resulted in injuries in 18/30 (60%), ranging from skin lacerations, joint dislocations, bone fractures to life-threatening intracranial hemorrhage. The injuries occurred most with drop attacks 8/9 (89%). Seizure-related falls or near falls resolved with immunotherapy in 24/32 (75%) whereas the responsiveness to anti-seizure medication alone was poor (4/32, 13%).
DISCUSSION
Our study demonstrates that seizure-related falls and near falls are common in LGI1-IgG autoimmune encephalitis. Early diagnosis, prompt immunotherapy initiation, and proper counseling are key to improving functional outcomes and preventing secondary injuries.
PubMed: 38938695
DOI: 10.1212/CPJ.0000000000200301 -
Frontiers in Immunology 2024Health-related quality of life is a key contributor to overall well-being, and this is becoming an increasingly prominent factor when making therapeutic choices in the... (Review)
Review
Health-related quality of life is a key contributor to overall well-being, and this is becoming an increasingly prominent factor when making therapeutic choices in the management of ANCA-associated vasculitis (AAV). Progress in available therapeutic strategies for AAV has resulted in this historically acute disease with a potentially fatal short-term outcome, becoming a relapsing-remitting chronic disorder. This new perspective on AAV means that patient survival should no longer be considered as the only major treatment target. Additional outcomes in this context that should be portrayed in order to consider a therapeutic approach as successful include patient quality of life, as well as the burden of treatment-induced morbidity. Comorbidities and impaired quality of life in patients with AAV, as with many other autoimmune diseases, may be a consequence of the disease itself as well as a result of the therapy employed. The AAV disease process may induce organ damage, including kidney failure and structural lung damage, and increase the risk of cardiovascular disease. On top of this, treatments employed to manage the disease may contribute further to the overall comorbidities burden. Furthermore, pre-existing comorbidities can increase AAV severity and may also be contraindications that limit potential therapeutic options. Quality of life is another central topic that can have a huge impact on patient wellbeing as well as adherence to treatment. Ongoing monitoring of comorbidity risk and of quality of life is thus key for successful AAV management. This process, however, may be complicated; the identification of the correct parameters on which to focus is not always straightforward and, more importantly, it is sometimes the symptoms that may appear trivial to physicians that are most detrimental to a patient's quality of life. With these shifts in treatment capabilities and understanding of patient burden, it is necessary to adjust the treatment paradigm accordingly. Treatment success is no longer defined solely by the control of disease activity; treatment success requires holistic improvement determined through the assessment of all aspects of the disease, ranging from disease control to comorbidity risk through to the assessment of health-related quality of life. This review explores the burden of AAV itself as well as treatment-related side effects with a special focus on the tools available to measure outcomes. The management of AAV has entered a new era with a strong focus on both the management and prevention of comorbidities as well as patient-reported outcomes, both of which are now considered key factors in defining treatment success.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Quality of Life; Treatment Outcome; Comorbidity; Disease Management
PubMed: 38938575
DOI: 10.3389/fimmu.2024.1409129 -
Frontiers in Immunology 2024Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently...
Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody-positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases.
Topics: Humans; Salivary Glands; Autoantibodies; Myositis; Female; Male; Lung; Middle Aged; Bronchoalveolar Lavage Fluid; Adult; B-Lymphocytes; Lung Diseases, Interstitial; Autoantigens; Antibodies, Antinuclear; Aged
PubMed: 38938569
DOI: 10.3389/fimmu.2024.1265792 -
Frontiers in Psychiatry 2024Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can... (Review)
Review
Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called "therapy-resistant depression". The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics. The integration of the flow of multi-omic information into molecular pathways may produce better outcomes than the current psychopharmacological approach, which targets singular molecular factors mainly related to the monoamine systems, disregarding the complex network of our organism. The concept of system biomedicine involves the integration and analysis of enormous datasets generated with different technologies, creating a "patient fingerprint", which defines the underlying biological mechanisms of every patient. This review, centered on precision medicine, explores the integration of multi-omic approaches as clinical tools for prediction in MDD at a single-patient level. It investigates how combining the existing technologies used for diagnostic, stratification, prognostic, and treatment-response biomarkers discovery with artificial intelligence can improve the assessment and treatment of MDD.
PubMed: 38938457
DOI: 10.3389/fpsyt.2024.1422939 -
Case Reports in Obstetrics and... 2024Autoimmune hemolytic anemia (AIHA) associated with solid tumors such as mature cystic teratomas is rare and poorly understood. Here, we report a successfully treated...
BACKGROUND
Autoimmune hemolytic anemia (AIHA) associated with solid tumors such as mature cystic teratomas is rare and poorly understood. Here, we report a successfully treated case of secondary AIHA in a mature cystic teratoma containing antibodies against red blood cells. . A 22-year-old woman was referred to our hospital with progressive anemia. Laboratory findings revealed hemolysis with a positive direct and indirect antiglobulin test. Imaging studies identified a left ovarian mass, suspected to be a mature cystic teratoma, which was later confirmed by histopathology after laparoscopic oophorocystectomy. The patient was treated with prednisolone, resulting in improved anemia. To examine the relationship between the tumor and AIHA, an indirect antiglobulin test was performed on the tumor contents. Stronger aggregations were observed at any concentration diluted by 10 times from 10 to 10,000 times of the tumor contents compared to the patient's serum. Additionally, immunofixation electrophoresis of the tumor contents revealed the presence of monoclonal immunoglobulin G-.
CONCLUSION
The presence of monoclonal IgG- in the tumor suggests intratumoral antibody production as a possible mechanism. Further research is necessary to elucidate the pathogenic relationship between such tumors and AIHA. The report also highlights the importance of considering secondary AIHA in patients with unexplained anemia and solid tumors.
PubMed: 38938323
DOI: 10.1155/2024/2223281 -
Turkish Journal of Haematology :... Jun 2024
PubMed: 38938201
DOI: 10.4274/tjh.galenos.2024.2024.0136 -
ESC Heart Failure Jun 2024Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there...
AIMS
Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti-inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF).
METHODS AND RESULTS
We present the rationale and design of the ARCHER Trial, an international multicentre, double-blind, randomized, placebo-controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow-up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs-troponin, NT-proBNP, markers of inflammation and endothelial function during the 12-week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper.
CONCLUSIONS
The ongoing ARCHER Trial is an international, multicentre, double-blind, randomized, placebo-controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.
PubMed: 38937900
DOI: 10.1002/ehf2.14889