Clinical Features Of Disease Research Articles

GluN2B subunit selective N-methyl-D-aspartate receptor ligands: Democratizing recent progress to assist the development of novel neurotherapeutics.

N-methyl-D-aspartate receptors (NMDARs) play essential roles in vital aspects of brain functions. NMDARs mediate clinical features of neurological diseases and thus, represent a potential therapeutic target for their treatments. Many findings implicated the GluN2B subunit of NMDARs in various neurological disorders including epilepsy, ischemic brain damage, and neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's chorea, and amyotrophic lateral sclerosis. Although a large amount of information is growing consistently on the importance of GluN2B subunit, however, limited recent data is available on how subunit-selective ligands impact NMDAR functions, which blunts the ability to render the diagnosis or craft novel treatments tailored to patients. To bridge this gap, we have focused on and summarized recently reported GluN2B selective ligands as emerging subunit-selective antagonists and modulators of NMDAR. Herein, we have also presented an overview of the structure-function relationship for potential GluN2B/NMDAR ligands with their binding sites and connection to CNS functionalities. Understanding of design rules and roles of GluN2B selective compounds will provide the link to medicinal chemists and neuroscientists to explore novel neurotherapeutic strategies against dysfunctions of glutamatergic neurotransmission.

Clinical and Gene Analysis of Fatty Acid Oxidation Disorders Found in Neonatal Tandem Mass Spectrometry Screening.

To investigate the clinical and gene mutation characteristics of fatty acid oxidative metabolic diseases found in neonatal screening. A retrospective analysis was performed on 29,948 neonatal blood tandem mass spectrometry screening samples from January 2018 to December 2021 in our neonatal screening centre. For screening positive, recall review is still suspected of fatty acid oxidation metabolic disorders in children as soon as possible to improve the genetic metabolic disease-related gene detection package to confirm the diagnosis. All diagnosed children were followed up to the deadline. Among 29,948 neonates screened by tandem mass spectrometry, 14 cases of primary carnitine deficiency, six cases of short-chain acyl coenzyme A dehydrogenase deficiency, two cases of carnitine palmitoyltransferase-I deficiency and one case of multiple acyl coenzyme A dehydrogenase deficiency were recalled. Except for two cases of multiple acyl coenzyme A dehydrogenase deficiency that exhibited [manifestations], the other 21 cases were diagnosed pre-symptomatically. Eight mutations of SLC22A5 gene were detected, including c.51C>G, c.403G>A, c.506G>A, c.1400C>G, c.1085C>T, c.706C>T, c.1540G>C and c.338G>A. Compound heterozygous mutation of CPT1A gene c.2201T>C, c.1318G>A, c.2246G>A, c.2125G>A and ETFA gene c.365G>A and c.699_701delGTT were detected, and new mutation sites were found. Neonatal tandem mass spectrometry screening is an effective method for identifying fatty acid oxidative metabolic diseases, but it should be combined with urine gas chromatography-mass spectrometry and gene sequencing technology. Our findings enrich the gene mutation profile of fatty acid oxidative metabolic disease and provide evidence for genetic counselling and prenatal diagnosis in families.

Early neurofilament light and glial fibrillary acidic protein levels improve predictive models of multiple sclerosis outcomes.

Early risk-stratification in multiple sclerosis (MS) may impact treatment decisions. Current predictive models have identified that clinical and imaging characteristics of aggressive disease are associated with worse long-term outcomes. Serum biomarkers, neurofilament (sNfL) and glial fibrillary acidic protein (sGFAP), reflect subclinical disease activity through separate pathological processes and may contribute to predictive models of clinical and MRI outcomes. We conducted a retrospective analysis of the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB study), where patients with multiple sclerosis are seen every 6 months and undergo Expanded Disability Status Scale (EDSS) assessment, have annual brain MRI scans where volumetric analysis is conducted to calculate T2-lesion volume (T2LV) and brain parenchymal fraction (BPF), and donate a yearly blood sample for subsequent analysis. We included patients with newly diagnosed relapsing-remitting MS and serum samples obtained at baseline visit and 1-year follow-up (both within 3 years of onset), and were assessed at 10-year follow-up. We measured sNfL and sGFAP by single molecule array at baseline visit and at 1-year follow-up. A predictive clinical model was developed using age, sex, Expanded Disability Status Scale (EDSS), pyramidal signs, relapse rate, and spinal cord lesions at first visit. The main outcome was odds of developing of secondary progressive (SP)MS at year 10. Secondary outcomes included 10-year EDSS, brain T2LV and BPF. We compared the goodness-of-fit of the predictive clinical model with and without sNfL and sGFAP at baseline and 1-year follow-up, for each outcome by area under the receiver operating characteristic curve (AUC) or R-squared. A total 144 patients with median MS onset at age 37.4 years (interquartile range: 29.4-45.4), 64% female, were included. SPMS developed in 25 (17.4%) patients. The AUC for the predictive clinical model without biomarker data was 0.73, which improved to 0.77 when both sNfL and sGFAP were included in the model (P=0.021). In this model, higher baseline sGFAP associated with developing SPMS (OR=3.3 [95%CI:1.1,10.6], P=0.04). Adding 1-year follow-up biomarker levels further improved the model fit (AUC=0.79) but this change was not statistically significant (P=0.15). Adding baseline biomarker data also improved the R-squared of clinical models for 10-year EDSS from 0.24 to 0.28 (P=0.032), while additional 1-year follow-up levels did not. Baseline sGFAP was associated with 10-year EDSS (ß=0.58 [95%CI:0.00,1.16], P=0.05). For MRI outcomes, baseline biomarker levels improved R-squared for T2LV from 0.12 to 0.27 (P<0.001), and BPF from 0.15 to 0.20 (P=0.042). Adding 1-year follow-up biomarker data further improved T2LV to 0.33 (P=0.0065) and BPF to 0.23 (P=0.048). Baseline sNfL was associated with T2LV (ß=0.34 [95%CI:0.21,0.48], P<0.001) and 1-year follow-up sNfL with BPF (ß=-2.53% [95%CI:-4.18,-0.89], P=0.003). Early biomarker levels modestly improve predictive models containing clinical and MRI variables. Worse clinical outcomes, SPMS and EDSS, are associated with higher sGFAP levels and worse MRI outcomes, T2LV and BPF, are associated with higher sNfL levels. Prospective study implementing these predictive models into clinical practice are needed to determine if early biomarker levels meaningfully impact clinical practice.

Epidemiological, clinical, radiographic, echocardiographic findings and outcome in client-owned guinea pigs (Cavia porcellus) with cardiac disease: 80 cases (2010-2021).

To characterize epidemiological, clinical, radiographic, and echocardiographic features of cardiac diseases in guinea pigs examined at a referral exotics center. 80 guinea pigs. Medical records of guinea pigs that had echocardiography performed between June 2010 and January 2021 were reviewed. The percentage of guinea pig patients with cardiovascular disease was 2.8%. Clinical signs included dyspnea (46/80), lethargy (18/80), and anorexia (10/80). The most common physical examination finding was heart murmur (10/80). Radiographic abnormalities included subjective cardiomegaly (37/67), pleural effusion (21/67), and increased lung opacity (40/67). Median (range) vertebral heart score on right lateral (48/67) and ventrodorsal (39/67) projections was 9.0 vertebrae (6.6 to 13.2 vertebrae) and 10.8 vertebrae (7.9 to 13.2 vertebrae), respectively. The most common echocardiographic diagnosis was cardiomyopathy (30/80), categorized as restrictive (11/30), hypertrophic (10/30), or dilated (9/10). Other cardiac diseases included cor pulmonale (21/80), pericardial effusion (18/80), congenital heart disease (6/80), acquired valvular disease (3/80), and cardiovascular mass (2/80). Congestive heart failure was present in 36 of 80. Median survival time from diagnosis was 2.5 months (95% CI, 1.1 to 6.2 months). Animals that died from heart disease had a significantly shorter survival time than those that died from a noncardiac disease (P = .02). On radiographs, cardiomegaly, pleural effusion, and alveolar or interstitial lung pattern should be considered as indications for echocardiography in guinea pigs. Cardiomyopathy (restrictive, hypertrophic, or dilated), cor pulmonale, and pericardial effusion were the most common echocardiographic diagnoses. Further studies on diagnosis and treatment of cardiovascular diseases in guinea pigs are needed.

Genetic prion diseases presenting as frontotemporal lobar degeneration: clinical features and diagnostic challenge

AbstractBackgroundElucidate the clinical and ancillary feature of genetic prion diseases (gPrDs) presenting with frontotemporal lobar degeneration (FTLD) in order to aid early identification, diagnosis, and referral for genotype testing.MethodGlobal data of gPrDs presenting with FTLD caused by prion protein gene (PRNP) mutations were collected from literature review and our records. Fifty‐one cases of typical FTLD and 136 of prion diseases admitted to our institution were included as controls. Clinical and ancillary data of the different groups were compared.ResultForty‐nine cases of gPrDs presenting with FTLD were identified, 23 of which were female. Twenty‐three mutations in PRNP have been reported to be associated with the FTLD, with P39L being the most commonly reported, seen in 4 families with 5 cases. Compared to FTLD or prion diseases, gPrDs presenting with FTLD is characterized by earlier onset age (median: 45 vs. 61/60 years) and stronger family history (81.6% vs. 27.5/13.2%). In addition, gPrDs presenting with FTLD exhibited shorter duration (median: 5 vs. 8 years), and a higher rate of clinical and ancillary features of prion diseases compared to FTLD. Compared to prion diseases, gPrDs presenting with FTLD had a longer duration of symptoms (median: 5 vs. 1.1 years), higher rates of frontotemporal atrophy (89.7% vs. 3.3%), lower rates of periodic short‐wave complexes on EEG (0% vs. 29.4%), and hyperintensity on MRI (25.0% vs. 83.0%). The frequency of the Val allele for codon 129 in PRNP carriers with FTLD was significantly higher than that reported in literature for gPrDs (33.3% vs. 19.2%).ConclusionGPrDs presenting with FTLD is characterized by early‐onset, strong family history, high frequency of the Val allele for codon 129 in PRNP. The clinical features of GPrDs presenting with FTLD is intermediate of the two distinct conditions, while the auxiliary features were closer to that of FTLD. Patients with these characteristics need to be considered for PRNP genotype testing.

Chest radiological features and their association with clinical manifestations in COVID-19 positive neonates and young infants

We report the Radiological findings in relation to the clinical features of coronavirus disease (COVID-19) in 37 symptomatic neonates and young infants (&lt;2 months of age) who presented with a sepsis-like picture and proved to be infected with COVID-19. Patients and methods: We reviewed, recorded, and analyzed the clinical findings in relation to the imaging features of coronavirus disease (COVID-19) in 37 symptomatic neonates and young infants (&lt;2 months of age) who presented with sepsis-like picture (fever, hypotonia, hypoactivity, cough, and poor feeding) and proved to be infected with COVID19 (PCR) between January 1, 2020, and June 1, 2020. Results: Our symptomatic newborns with COVID-19 infection had increased pulmonary vascularity in 6.2%, slightly accentuated central lung vascularity in 12.5%, and prominent hilar shadows with increased linear lung shadowing in the perihilar and precardiac in 34%. Increased linear lung shadowing with a tiny beaded-like appearance more distributed peripherally and at lower lobes occurred in 28%. Superadded peri-bronchial cuffing and perivascular haziness and lace-like fine linear appearance of interstitium occurred in 9.3%. Ground glass fine opacities (GGO) scattered in two or more lobes of both lungs appeared in 15.6%. Only 6.2% of symptomatic newborns showed superadded consolidations in both lungs, mainly peripherally oriented. Correlation with clinical severity of the disease (requirement of oxygen and assisted ventilation) proved that the appearance of GGO without consolidations was associated with moderate clinical severity, while the appearance of consolidations was associated with marked disease severity. Conclusions: These findings brought more attention and understanding of the radiological manifestations and their association with the clinical severity in COVID19 positive newborns and young infants.

Meta-analysis of the association between RNF213 polymorphisms and clinical features of moyamoya disease in Asian population

BackgroundWe performed this study to explore the relationship between ring finger protein 213 (RNF213) gene polymorphisms and clinical features in moyamoya disease (MMD). MethodsElectronic databases (PubMed, Google Scholar, Embase, Scopus, Cochrane Library) were conducted from inception to May 15th, 2022. Odds ratios (ORs) with 95 % confidence intervals (CIs) were generated as effect size for binary variants. Subgroup analyses were performed by the RNF213 polymorphisms. Sensitivity was used to examine the robustness of associations. ResultsA total of 16 articles and 3061 MMD patients were included and the association of five RNF213 polymorphisms on 9 clinical features of MMD were identified. Patients under 18 years of age at onset, familial MMD, cerebral ischemic stroke and posterior cerebral artery involvement (PCi) were significantly more common in mutant type compared with wild type of RNF213. Compared with each wild type, subgroup analysis showed that rs11273543 and rs9916351 remarkably increased risk of MMD on early onset, but rs371441113 evidently delayed the onset of MMD. Rs112735431 in mutant type was significantly higher than wild type in patients with PCi. Subgroup analysis in mutant type showed that rs112735431 conspicuously decreased intracerebral/ intraventricular hemorrhage (ICH/IVH) risk and yet rs148731719 obviously increased the risk in ICH/IVH. ConclusionMore attention should be paid to patients on whom the ischemic MMD occurs younger than 18 years old. RNF213 polymorphism screening and cerebrovascular imaging examination should be performed to evaluate intracranial vascular involvement, to achieve early detection and early treatment and avoid more serious cerebrovascular events.

Characterization of neuropathology in ovine CLN5 and CLN6 neuronal ceroid lipofuscinoses (Batten disease).

Sheep with naturally occurring CLN5 and CLN6 forms of neuronal ceroid lipofuscinoses (Batten disease) share the key clinical features of the human disease and represent an ideal model system in which the clinical efficacy of gene therapies is developed and test. However, it was first important to characterize the neuropathological changes that occur with disease progression in affected sheep. This study compared neurodegeneration, neuroinflammation, and lysosomal storage accumulation in CLN5 affected Borderdale, CLN6 affected South Hampshire, and Merino sheep brains from birth to end-stage disease at ≤24 months of age. Despite very different gene products, mutations, and subcellular localizations, the pathogenic cascade was remarkably similar for all three disease models. Glial activation was present at birth in affected sheep and preceded neuronal loss, with both spreading from the visual and parieto-occipital cortices most prominently associated with clinical symptoms to the entire cortical mantle by end-stage disease. In contrast, the subcortical regions were less involved, yet lysosomal storage followed a near-linear increase across the diseased sheep brain with age. Correlation of these neuropathological changes with published clinical data identified three potential therapeutic windows in affected sheep-presymptomatic (3 months), early symptomatic (6 months), and a later symptomatic disease stage (9 months of age)-beyond which the extensive depletion of neurons was likely to diminish any chance of therapeutic benefit. This comprehensive natural history of the neuropathological changes in ovine CLN5 and CLN6 disease will be integral in determining what impact treatment has at each of these disease stages.

Development of the global inflammatory bowel disease visualization of epidemiology studies in the 21st century (GIVES-21)

BackgroundThere is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development.MethodsGlobal IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn’s disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis.ResultsThrough November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting.ConclusionsThe GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.

Clinical Features of COVID-19 in Pediatric Rheumatic Diseases: 2020-2022 Survey of the Pediatric Rheumatology Association of Japan.

Coronavirus disease 2019 (COVID-19) in children can be compounded by concurrent diseases and immunosuppressants. For the first time, we aimed to report the clinical features of concurrent COVID-19 and pediatric rheumatic disease (PRD) in Japan. Pediatric Rheumatology Association of Japan members were surveyed between 1 April 2020 and 31 August 2022. Outcome measurements included the clinical features of concurrent PRD and COVID-19. Questionnaire responses were obtained from 38 hospitals. Thirty-one hospitals (82%) had children with PRD and COVID-19. The female-to-male ratio in these children (n = 156) was 7:3, with half aged 11-15 years. The highest proportion of children with PRD and COVID-19 was accounted for by juvenile idiopathic arthritis (52%), followed by systemic lupus erythematosus (24%), juvenile dermatomyositis (5%), scleroderma (4%), and Takayasu arteritis (3%). Of children with PRD, a significant majority (97%) were found to be asymptomatic (10%) or presented with mild symptoms (87%) of the COVID-19 infection. No severe cases or deaths were observed. Regarding the use of glucocorticoids, immunosuppressants, or biologics for PRD treatment before COVID-19, no significant difference was found between asymptomatic/mild and moderate COVID-19 in children with PRD. Therefore, COVID-19 is not a threat to children with PRD in Japan.

Exploring HTRA1-Autosomal Dominant Disease: Literature Review of Clinical Features and Molecular Mechanisms

Heterozygous HTRA1-autosomal dominant disease is a gradually recognized hereditary cerebral small vessel disease (cSVD) characterized by debilitating conditions and extensive white matter hyperintensities (WMHs), but doubts remain on the underlying mechanisms of this disease. This review summarizes the clinical, MRI, and molecular genetics features of heterozygous HTRA1-autosomal dominant disease in combination with two better-studied hereditary cSVDs. A total of 31 mutations in HTRA1-autosomal dominant cases documented between 2020 and 2023 were also reviewed, characterizing the mutation features and clinical manifestations. This review aims to gain better insight into the unique characteristics of the disease and its correlations with other hereditary cSVDs.

Combined Clinical, Molecular, and Muscle Biopsy Approach to Unveil Prevalence and Clinical Features of Rare Neuromuscular and Mitochondrial Diseases in Patients With Cardiomyopathies.

Combined Clinical, Molecular, and Muscle Biopsy Approach to Unveil Prevalence and Clinical Features of Rare Neuromuscular and Mitochondrial Diseases in Patients With Cardiomyopathies.

Citrin Deficiency: Clinical and Nutritional Features.

SLC25A13 gene mutations are responsible for diseases related to citrin deficiency (CD), such as neonatal intrahepatic cholestasis caused by citrin deficiency and adult-onset type II citrullinemia (CTLN2). From childhood to adulthood, CD patients are apparently healthy due to metabolic compensation with peculiar dietary habits-disliking high-carbohydrate foods and liking fat and protein-rich foods. Carbohydrate overload and alcohol consumption may trigger the sudden onset of CTLN2, inducing hyperammonemia and consciousness disturbance. Well-compensated asymptomatic CD patients are sometimes diagnosed as having non-obese (lean) non-alcoholic fatty liver disease and steatohepatitis, which have the risk of developing into liver cirrhosis and hepatocellular carcinoma. CD-induced fatty liver demonstrates significant suppression of peroxisome proliferator-activated receptor α and its downstream enzymes/proteins involved in fatty acid transport and oxidation and triglyceride secretion as a very low-density lipoprotein. Nutritional therapy is an essential and important treatment of CD, and medium-chain triglycerides oil and sodium pyruvate are useful for preventing hyperammonemia. We need to avoid the use of glycerol for treating brain edema by hyperammonemia. This review summarizes the clinical and nutritional features of CD-associated fatty liver disease and promising nutritional interventions.

Analysis of Circulating Tumor DNA in Synchronous Metastatic Colorectal Cancer at Diagnosis Predicts Overall Patient Survival.

Sporadic colorectal cancer (sCRC) initially presents as metastatic tumors in 25-30% of patients. The 5-year overall survival (OS) in patients with metastatic sCRC is 50%, falling to 10% in patients presenting with synchronous metastatic disease (stage IV). In this study, we systematically analyzed the mutations of RAS, PIK3CA and BRAF genes in circulating tumor DNA (ctDNA) and tumoral tissue DNA (ttDNA) from 51 synchronous metastatic colorectal carcinoma (SMCC) patients by real-time PCR, and their relationship with the clinical, biological and histological features of disease at diagnosis. The highest frequency of mutations detected was in the KRAS gene, in tumor biopsies and plasma samples, followed by mutations of the PIK3CA, NRAS and BRAF genes. Overall, plasma systematically contained those genetic abnormalities observed in the tumor biopsy sample from the same subject, the largest discrepancies detected between the tumor biopsy and plasma from the same patient being for mutations in the KRAS and PIK3CA genes, with concordances of genotyping results between ttDNA and ctDNA at diagnosis of 75% and 84%, respectively. Of the 51 SMCC patients in the study, 25 (49%) showed mutations in at least 1 of the 4 genes analyzed in patient plasma. From the prognostic point of view, the presence and number of the most common mutations in the RAS, PIK3CA and BRAF genes in plasma from SMCC patients are independent prognostic factors for OS. Determination of the mutational status of ctDNA in SMCC could be a key tool for the clinical management of patients.

A Randomized Controlled Trial of Probiotics Targeting Gut Dysbiosis in Huntington's Disease.

Gastrointestinal symptoms are clinical features of Huntington's disease (HD), which adversely affect people's quality of life. We recently reported the first evidence of gut dysbiosis in HD gene expansion carriers (HDGECs). Here, we report on a randomized controlled clinical trial of a 6-week probiotic intervention in HDGECs. The primary objective was to determine whether probiotics improved gut microbiome composition in terms of richness, evenness, structure, and diversity of functional pathways and enzymes. Exploratory objectives were to determine whether probiotic supplementation improved cognition, mood, and gastrointestinal symptoms. Forty-one HDGECs, including 19 early manifest and 22 premanifest HDGECs were compared with 36 matched-healthy controls (HCs). Participants were randomly assigned probiotics or placebo and provided fecal samples at baseline and 6-week follow-up, which were sequenced using 16S-V3-V4 rRNA to characterize the gut microbiome. Participants completed a battery of cognitive tests and self-report questionnaires measuring mood and gastrointestinal symptoms. HDGECs had altered gut microbiome diversity when compared to HCs, indicating gut dysbiosis. Probiotic intervention did not ameliorate gut dysbiosis or have any effect on cognition, mood, or gastrointestinal symptoms. Gut microbiome differences between HDGECs and HCs were unchanged across time points, suggesting consistency of gut microbiome differences within groups. Despite the lack of probiotic effects in this trial, the potential utility of the gut as a therapeutic target in HD should continue to be explored given the clinical symptomology, gut dysbiosis, and positive results from probiotics and other gut interventions in similar neurodegenerative diseases.

Clinical, radiological and pathological features of anti-MDA5 antibody-associated interstitial lung disease

IntroductionTo investigate the clinical, radiographic and pathological features of interstitial lung disease (ILD) in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5+DM).MethodsWe retrospectively analysed the medical records of patients...

Research Strategy for the Development of a Quality-of-Life Decision-Making Model for Older Patients With Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a deadly cancer, especially for patients over 60 years of age who face the dilemma of choosing the best treatment during a time of crisis. Current research in the older AML population is focused on survival without addressing quality of life (QOL). Survival and QOL data are essential for patients to decide which treatment best aligns with their goals, whether for survival or improved QOL. Research aims: The aims of this study are to: (1) Describe differences in QOL among newly diagnosed older AML patients receiving intensive chemotherapy compared with nonintensive chemotherapy (at baseline, and days 30, 60, 90, and 180 post treatment); (2) Identify the individual clinical disease characteristics and patient factors of newly diagnosed AML patients that predict QOL among those receiving two treatment intensities; and (3) Design a patient decision-making model that integrates the significant clinical disease and patient factor predictors of QOL for newly diagnosed older AML patients. Methods: An exploratory observational design will be used to address aims 1 and 2. Data will be collected from 200 patients ≥ 60 years of age with newly diagnosed AML. Subjects will complete the Functional Assessment of Cancer Therapy-Leukemia, Brief Fatigue Inventory, and Memorial Symptom Assessment Short Form within 7 days of beginning new treatment and at days 30, 60, 90 and 180. Clinical disease characteristics will be completed by the health-care team. A patient decision-making model will be developed to provide survival and quality-of-life data for intensive and nonintensive chemotherapy.

DEMOGRAPHIC AND CLINICAL CORRELATES OF INFECTIVE ENDOCARDITIS IN NON-RHEUMATIC AORTIC VALVE DISEASE: DESCRIPTIVE INSIGHTS FROM NATIONWIDE INPATIENT STUDY

Objective: To delineate the clinical and demographic characteristics of non-rheumatic aortic valve disease (NRAVD) by treatment modalities, and to evaluate factors that increase the risk of infective endocarditis in inpatients with NRAVD. Methods: A retrospective cross-sectional study was performed with a total of 109,000 adult patients (age 18-90 years) primarily managed for NRAVD selected from the nationwide inpatient sample (NIS, 2019) in the United States. The study sample was divided based on treatment into medical therapy vs. transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). Alogistic regression model was used to evaluate the odds ratio (OR) of the association for infective endocarditis in inpatients with NRAVD. Results:Ahigher prevalence of infective endocarditis was recorded in SAVR (1.1%) compared to the inpatients managed with medical therapy (0.8%) and TAVR (0.1%). Patients with major loss of body functioning were managed in higher proportions with SAVR (42.8%) and medical therapy (41.9%) instead of TAVR (30.2%). In-hospital mortality was higher in medical therapy (4.1%) compared to SAVR (2.1%) and TAVR (1.2%). The risk of infective endocarditis was signicantly higher in patients with NRAVD &lt;65 years of age (OR 2.85), whites (OR 1.62), hypertension (OR 1.61), and drug abuse (OR 3.49). Conclusion: The likelihood of IE increases in younger patients with comorbid hypertension and drug abuse, and major loss of body functioning. A higher proportion of the inpatients managed with SAVR had IE compared to those with TAVR and medical therapy. Longitudinal studies are required to assess the risk and outcomes of related to the treatment for NRAVD

Management of Metastatic Prostate Cancer

Androgen deprivation therapy is a well-established standard of care for the management of metastatic prostate cancer; however, recent studies have investigated additional therapeutic options, escalation strategies, and primary directed therapy for patients with advanced disease. Treatment decisions are based on clinical parameters, disease characteristics, and patient factors. At the NCCN 2023 Annual Conference, a panel of experts used 3 case studies to develop an evidence-based approach for the treatment of patients with metastatic prostate cancer. The session focused on the current research regarding both systemic and local therapy options in each clinical context.

Paediatric autoimmune diseases with ELANE mutations associated with neutropenia

ObjectiveTo explore the clinical characteristics of autoimmune diseases in children with ELANE mutations.MethodsThree cases of children with ELANE mutations manifesting as autoimmune diseases, who were under treatment from April 2020 to May 2021, were retrospectively analysed.ResultsAmong the three children, two were boys aged 15 years and 22 months (cases 1 and 3) respectively, and the other one was a 22-month-old girl (case 2). All the cases had recurrent infections. Case 1 presented with cyclic neutropenia and systemic lupus erythematosus (SLE). Case 2 presented with severe neutropenia and autoimmune haemolytic anaemia (AHIA). Case 3 presented with severe neutropenia and anti-neutrophil cytoplasm antibodies (ANCA)-associated small vasculitis. Genetic tests showed that they all had heterozygous mutations in the ELANE gene. Case 1 was treated with methylprednisolone and hydroxychloroquine sulphate for 2 years, making neutrophil level return to normal. Case 2 received allogeneic hematopoietic stem cell transplantation and has stopped taking antibiotics, steroids and all the immunosuppressors. Case 3 received subcutaneous injections of granulocyte colony-stimulating factor, oral prednisone and cyclophosphamide. The boy in case 3 has been followed up for one year, and his absolute neutrophil count has increased to 1.56 × 109/L.ConclusionPatients with ELANE mutations, combined with autoimmune diseases, may have recurrent infections. Disease-modifying antirheumatic drugs (DMARDs) are effective for autoimmune diseases. Autoimmune diseases with ELANE mutations associated with neutropenia can be cured through allogeneic hematopoietic stem cell transplantation.