Natural History Of Disease Research Articles

Rapid diagnostic genome sequencing for genetic diseases in inpatients: an emerging new standard-of-care

Over 7,300 single locus (Mendelian) genetic diseases have a known molecular cause. While individually rare, collectively these diseases have a prevalence of at least 2% and are a leading cause of infant mortality in high income countries. More than 500 genetic diseases have effective treatments. Unfortunately, genetic diseases are often still mis-diagnosed and mis-treated as common conditions or go undiagnosed for years. First described in 2012, phenotype-guided genome sequencing is emerging as the gold standard for diagnosis of Mendelian disease.1 For acutely ill inpatients, rapid genome sequencing can provide a molecular diagnosis (or rule out suspected genetic disorders) in a day.2 From 2012 to 2021, 31 clinical studies documented the diagnostic and clinical utility of rapid genome or exome sequencing in acutely ill children.3 Several studies in different healthcare systems have shown that rapid genome sequencing is cost-effective as a first-tier test in children with suspected genetic diseases who are receiving intensive care, and provision of rapid diagnostic genome sequencing is becoming policy in this population in several countries. Early diagnosis is enabling early implementation of precision therapy. The impact of the latter on the natural history of genetic diseases is starting to become evident.

Targeted Therapy for MPNs: Going Beyond JAK Inhibitors.

JAK inhibition is an effective means of controlling symptom burden and improving splenomegaly in patients with myeloproliferative neoplasms (MPNs). However, a majority of patients treated with JAK inhibition will have disease progression with long-term use. In In this review, we focus on the investigation of novel targeted agents beyond JAK inhibitors both in the chronic phase of disease and in the accelerated/blast phase of disease. Relevant targeted therapies in MPNs include BET inhibitors, BCL inhibitors, LSD1 inhibitors, PI3K inhibitors, IDH inhibitors, telomerase inhibitors, and MDM2 inhibitor. Agents within these classes have been investigated either as monotherapy or in combination with a JAK inhibitor. We summarize the prospective data for these agents along with detailing the ongoing phase III trials incorporating these agents. While JAK inhibition has been a mainstay of therapy in MPNs, a majority of patients will have disease of progression. JAK inhibitors also have limited anti-clonal effect and do not impact the rate of progression to the blast phase of disease. The novel therapies detailed in this review not only show promise in ameliorating the symptom burden of MPNs but may be able to alter the natural history of disease.

Continuous glucose monitoring for children with hypoglycaemia: Evidence in 2023.

In 2023, childhood hypoglycaemia remains a major public health problem and significant risk factor for consequent adverse neurodevelopment. Irrespective of the underlying cause, key elements of clinical management include the detection, prediction and prevention of episodes of hypoglycaemia. These tasks are increasingly served by Continuous Glucose Monitoring (CGM) devices that measure subcutaneous glucose at near-continuous frequency. While the use of CGM in type 1 diabetes is well established, the evidence for widespread use in rare hypoglycaemia disorders is less than convincing. However, in the few years since our last review there have been multiple developments and increased user feedback, requiring a review of clinical application. Despite advances in device technology, point accuracy of CGM remains low for children with non-diabetes hypoglycaemia. Simple provision of CGM devices has not replicated the efficacy seen in those with diabetes and is yet to show benefit. Machine learning techniques for hypoglycaemia prevention have so far failed to demonstrate sufficient prediction accuracy for real world use even in those with diabetes. Furthermore, access to CGM globally is restricted by costs kept high by the commercially-driven speed of technical innovation. Nonetheless, the ability of CGM to digitally phenotype disease groups has led to a better understanding of natural history of disease, facilitated diagnoses and informed changes in clinical management. Large CGM datasets have prompted re-evaluation of hypoglycaemia incidence and facilitated improved trial design. Importantly, an individualised approach and focus on the behavioural determinants of hypoglycaemia has led to real world reduction in hypoglycaemia. In this state of the art review, we critically analyse the updated evidence for use of CGM in non-diabetic childhood hypoglycaemia disorders since 2020 and provide suggestions for qualified use.

A parametric model to jointly characterize rate, duration, and severity of exacerbations in episodic diseases

BackgroundThe natural history of many chronic diseases is characterized by periods of increased disease activity, commonly referred to as flare-ups or exacerbations. Accurate characterization of the burden of these exacerbations is an important research objective.MethodsThe purpose of this work was to develop a statistical framework for nuanced characterization of the three main features of exacerbations: their rate, duration, and severity, with interrelationships among these features being a particular focus. We jointly specified a zero-inflated accelerated failure time regression model for the rate, an accelerated failure time regression model for the duration, and a logistic regression model for the severity of exacerbations. Random effects were incorporated into each component to capture heterogeneity beyond the variability attributable to observed characteristics, and to describe the interrelationships among these components.ResultsWe used pooled data from two clinical trials in asthma as an exemplary application to illustrate the utility of the joint modeling approach. The model fit clearly indicated the presence of heterogeneity in all three components. A novel finding was that the new therapy reduced not just the rate but also the duration of exacerbations, but did not have a significant impact on their severity. After controlling for covariates, exacerbations among more frequent exacerbators tended to be shorter and less likely to be severe.ConclusionsWe conclude that a joint modeling framework, programmable in available software, can provide novel insights about how the rate, duration, and severity of episodic events interrelate, and enables consistent inference on the effect of treatments on different disease outcomes.Trial registration Ethics approval was obtained from the University of British Columbia Human Ethics Board (H17-00938).

Prevalence, Natural History, and Nonoperative Treatment of Rotator Cuff Disease

Rotator cuff disease is extremely common, affecting between 6.8% and 22.4% of the population over age 40. Tear prevalence, size, likelihood of progression, and retear rates after surgical repair are all related to increasing age. These data suggest that asymptomatic rotator cuff tears are a process related to aging, and the description of this as a “tear” may be inaccurate. In addition to age, other nonmodifiable variables related to the presence and progression of rotator cuff tears include male sex, family history, and hand dominance. Smoking and certain disease states (diabetes, hypertension, serum lipid disorders) are potentially modifiable influences on rotator cuff disease. The relationship between symptoms and the presence of a rotator cuff tear and the progression of a rotator cuff tear are not robust. As fewer than 95% of people with rotator cuff tears come to surgery, the majority of rotator cuff tears are either asymptomatic or mildly symptomatic. Approximately half of existing rotator cuff tears progress over time. Those that progress more rapidly are more likely to have symptoms as the ability to compensate through teres minor hypertrophy and other adaptive mechanisms are exceeded. Both surgery and nonoperative treatments are effective at treating symptoms in patients with rotator cuff disease, but at this time it is not known which treatment is better for which patients. While some authors recommend repair for younger patients with smaller tears, the data on whether this approach can modify the natural history of rotator cuff disease is lacking.

OCT and OCT Angiography Update: Clinical Application to Age-Related Macular Degeneration, Central Serous Chorioretinopathy, Macular Telangiectasia, and Diabetic Retinopathy.

Similar to ultrasound adapting soundwaves to depict the inner structures and tissues, optical coherence tomography (OCT) utilizes low coherence light waves to assess characteristics in the eye. Compared to the previous gold standard diagnostic imaging fluorescein angiography, OCT is a noninvasive imaging modality that generates images of ocular tissues at a rapid speed. Two commonly used iterations of OCT include spectral-domain (SD) and swept-source (SS). Each comes with different wavelengths and tissue penetration capacities. OCT angiography (OCTA) is a functional extension of the OCT. It generates a large number of pixels to capture the tissue and underlying blood flow. This allows OCTA to measure ischemia and demarcation of the vasculature in a wide range of conditions. This review focused on the study of four commonly encountered diseases involving the retina including age-related macular degeneration (AMD), diabetic retinopathy (DR), central serous chorioretinopathy (CSC), and macular telangiectasia (MacTel). Modern imaging techniques including SD-OCT, TD-OCT, SS-OCT, and OCTA assist with understanding the disease pathogenesis and natural history of disease progression, in addition to routine diagnosis and management in the clinical setting. Finally, this review compares each imaging technique's limitations and potential refinements.

Aquaporins as Prognostic Biomarker in Prostate Cancer.

Prostate cancer is a complex heterogeneous disease that affects millions of males worldwide. Despite rapid advances in molecular biology and innovation in technology, few biomarkers have been forthcoming in prostate cancer. The currently available biomarkers for the prognosis of prostate cancer are inadequate and face challenges, thus having limited clinical utility. To date, there are a number of prognostic and predictive biomarkers identified for prostate cancer but lack specificity and sensitivity to guide clinical decision making. There is still tremendous scope for specific biomarkers to understand the natural history and complex biology of this heterogeneous disease, and to identify early treatment responses. Accumulative studies indicate that aquaporins (AQPs) a family of membrane water channels may serve as a prognostic biomarker for prostate cancer in monitoring disease advancement. In the present review, we discuss the existing prostate cancer biomarkers, their limitations, and aquaporins as a prospective biomarker of prognostic significance in prostate cancer.

Effect Modification by Age and Gender in the Correlation Between Diabetes Mellitus, Hypertension, and Obesity.

Literature has reported differences in the epidemiology or natural history of non-communicable diseases among both the male and female sexes. Stratification of multimorbidity burden based on sex is crucial to identify and implement targeted prevention and control interventions for chronic diseases. To determine the burden of hypertension, type-2 diabetes mellitus, and obesity; and to compare the related multimorbidity among male and female patients. The study was a retrospective analysis of 375 802 medical records from primary care centers. Data was extracted from March 2022 to March 2023. A multivariate probit estimation methodology was employed using a 3-equations multivariate multiple probit model to jointly estimate the association of a person's sex with the diagnosis of the 3 chronic conditions: obesity, diabetes, and hypertension. A multinomial logistic regression analysis was conducted to allow each unique combination of these 3 chronic diseases. Females had a relatively higher proportion of obesity (58.1% vs 41.2%), obesity and diabetes only (58.9% vs 41.1%), obesity and hypertension (63.6% vs 36.4%), and joint diagnosis with 3 conditions (65.7% vs 34.3%). Females' participants consistently had a significantly higher likelihood of diagnosis compared with males except for diabetes (OR = 0.59, 95% CI: 0.56-0.62) and the combination of only diabetes and hypertension (OR = 0.67, 95% CI: 0.61-0.74). The likelihood of other combinations ranged from 1.04 (95% CI: 0.98-1.10) for only hypertension to 2.30 (95% CI: 2.10-2.53) for the joint diagnosis of all 3 conditions. An increased likelihood of a single or combined occurrence of 3 chronic conditions was observed with increased age. The multimorbidity distribution for diabetes mellitus, hypertension, and obesity differs significantly among male and female patients. The overall burden of morbidity, and mortality, however, tends to rise after 46 years of age, with the highest burden among individuals above 60 years of age.

REVIEW OF THE NATURE OF ANTI/INFLAMMATORY AND PRO-INFLAMMATORY CYTOKINE REGULATION IN DIFFERENT PERIODS OF PLASMA CELL MYELOMA NATURAL HISTORY IN THE CHORNOBYL NPP ACCIDENT SURVIVORS.

identify the nature of anti-inflammatory and pro-inflammatory cytokine regulation in different periods of plasma cell myeloma (PCM) natural history with evaluation of its role as a prognostic criterion for the disease course in the Chornobyl NPP (ChNPP) accident survivors. Levels of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines both with their relationship were studied in the stage I-II and stage III PCM patients (n = 74) in different periods of the disease natural history i.e. remission/stabilization and progression. Study groups included the ChNPP accident survivors (n = 35) and non-irradiated subjects (n = 39). Immunoenzymatic method was applied using the Vector-Best CJSC commercial kits. There was a unidirectional increase in the levels of IL-6, TNF-α, and IL-10 in irradiated persons, and an elevation of IL-6 and TNF-α concentration but with a decreased level of IL-10 in non-irradiated subjects compared to control at the time of PCM diagnosis. Period of the disease remission/stabilization in PCM stage I-II patients featured a decrease in IL-6 concentration regardless of the exposure to ionizing radiation, while TNF-α content remained at the level of the control group. There was a significant increase in IL-6 concentration in both study groups during the disease relapse, while TNF-α level remained unchanged compared to stabilization phase of the disease. According to the obtained data a certain contribution of radiation exposure to the PCM pathogenesis as a possible predictor of the exacerbated disease course cannon be excluded. Determining the serum level of pro-inflammatory and anti-inflammatory cytokines (IL-6, TNF-α and IL-10 respectively) provides advancement in assessment of the PCM course and predict the effectiveness of administration of therapy protocols.

Evolving epidemiology of transthyretin amyloid cardiomyopathy due to increased recognition in women

BackgroundTransthyretin amyloid cardiomyopathy (ATTR-CM), particularly wild type (wtATTR-CM), is thought to mainly affect men. Non-invasive diagnosis and approved therapeutics have been associated with increased disease recognition. We investigated the trajectory of ATTR-CM diagnosis in women. MethodsThis observational study utilized data collected on 140 consecutive ATTR-CM patients diagnosed between 2005 and 2022 who are followed at the Oregon Health and Science University Amyloidosis Clinic. Subgroup analysis was performed on patients with wtATTR-CM which included 113 subjects (80.1%). The proportion of women among patients diagnosed with ATTR-CM prior to 2019 was compared with that of those diagnosed 2019–2022 (2019 was the year of tafamidis approval by the FDA). The clinical characteristics of male and female ATTR-CM patients were compared as well. ResultsOf the 140 ATTR-CM patients, 16 (11.4%) were women (age 77 ± 9 years) and 124 (88.6%) were men (age 76 ± 9 years). There was an increase in the rate of women diagnosed with ATTR-CM from pre 2019 to 2019–2022 in the overall cohort (4/68 [5.9%] vs 12/72 [16.7%]) and wild type subgroup (0/51 [0%] vs 7/62 [11.3%]). There were several differences in baseline clinical characteristics between women and men in this cohort, yet all women had a clear clinical phenotype of ATTR-CM. ConclusionsThere has been a significant increase in the rate of wtATTR-CM diagnoses in women, who presented with clear phenotypes of ATTR-CM. Further studies are needed to understand the effect of increased recognition of ATTR-CM in women on disease epidemiology, natural history, and outcomes.

Bayesian Strategies in Rare Diseases.

Bayesian strategies for planning and analyzing clinical trials have become a viable choice, especially in rare diseases where drug development faces many challenges and stakeholders are interested in innovations that may help overcome them. Disease natural history and clinical outcomes occurrence and variability are often poorly understood. Standard trial designs are not optimized to obtain adequate safety and efficacy data from small numbers of patients. Bayesian methods are well-suited for adaptive trials, with an accelerated learning curve. Using Bayesian statistics can be advantageous in that design choices and their consequences are considered carefully, continuously monitored, and updated where necessary, which ultimately provides a natural and principled way of seamlessly combining prior clinical information with data, within a solid decision theoretical framework. In this article, we introduce the Bayesian option in the rare disease context to support clinical decision-makers in selecting the best choice for their drug development project. Many researchers in drug development show reluctance to using Bayesian statistics, and the top-two reported barriers are insufficient knowledge of Bayesian approaches and a lack of clarity or guidance from regulators. Here we introduce concepts of borrowing, extrapolation, adaptation, and modeling and illustrate them with examples that have been discussed or developed with regulatory bodies to show how Bayesian strategies can be applied to drug development in rare diseases.

Busting the myth of methotrexate chronic hepatotoxicity.

Methotrexate is a key component of the treatment of inflammatory rheumatic diseases and the mainstay of therapy in rheumatoid arthritis. Hepatotoxicity has long been a concern for prescribers envisaging long-term treatment with methotrexate for their patients. However, the putative liver toxicity of methotrexate should be evaluated in the context of advances in our knowledge of the pathogenesis and natural history of liver disease, especially non-alcoholic fatty liver disease (NAFLD). Notably, patients with NAFLD are at increased risk for methotrexate hepatotoxicity, and methotrexate can worsen the course of NAFLD. Understanding the mechanisms of acute hepatotoxicity can facilitate the interpretation of elevated concentrations of liver enzymes in this context. Liver fibrosis and the mechanisms of fibrogenesis also need to be considered in relation to chronic exposure to methotrexate. A number of non-invasive tests for liver fibrosis are available for use in patients with rheumatic disease, in addition to liver biopsy, which can be appropriate for particular individuals. On the basis of the available evidence, practical suggestions for pretreatment screening and long-term monitoring of methotrexate therapy can be made for patients who have (or are at risk for) chronic liver disease.

953: INFLAMMATORY MYOFIBROBLASTIC TUMOR PRESENTING AS A LUNG NODULE: A CASE REPORT

Introduction: Inflammatory Myofibroblastic Tumors are a group of soft tissue neoplasms constituting a mixture of spindle-shaped myofibroblasts or fibroblasts and a variable amount of inflammatory cells with a predilection for the lung often presenting with non-specific symptoms. They represent less than 1% of adult lung tumors. Histopathologic and immunohistochemical analysis of a biopsy specimen is the mainstay of diagnosis. Description: A 30-year-old male presented to the ER with flank pain and episodes of small volume hemoptysis intermittently for the last six years. At presentation, a computed tomography angiography (CTA) of the chest revealed a cavitary nodule of 24 mm at the largest diameter containing rounded soft tissue mass arising adjacent to the right posterior basal segmental bronchus along with adjacent ground glass airspace opacities likely reflecting pulmonary haemorrhage which was confirmed on bronchoscopy revealing fresh blood emanating from the posterior basal segment of the right lower lobe with no endobronchial lesion. Bronchoalveolar lavage (BAL) of the segment was performed with cultures ultimately turning negative. At a later date, a robot-assisted navigational bronchoscopy-guided transbronchial needle aspiration of the lesion was performed. Histopathology results were significant for spindle cells arranged in a storiform to a haphazard pattern. The spindle cells had basophilic cytoplasm and elongated nuclei with fine chromatin. Immunostains of the tumor cells were positive for CD56, CD68, and CD34 (focal), SMA and ALK and negative for cytokeratins AE1/AE3, CK8/18, TTF-1, synaptophysin, chromogranin, S100, desmin, and CD117, SS18-SSX, STAT6, HHV-8, SOX10, CD30, and langerin. These findings supported the diagnosis of an inflammatory myofibroblastic tumor. Discussion: Chest imaging is crucial for early identification. Complete surgical excision provides long-term survival benefits, preventing local recurrence and metastasis. Corticosteroids can be used when the mass is unresectable. If ALK-1 is positive, crizotinib is beneficial in some cases. Our case highlights the need for further investigative studies to establish the natural history of this neoplastic disease and discover appropriate medical management for it.

2045. IVAC Plus in the Time of COVID-19: An Imperfect Metric?

Abstract Background Prior to the COVID-19 pandemic, the incidence of infection related ventilator associated complications plus possible ventilator associated pneumonias (IVAC+) was decreasing; however, as the number of COVID-19 hospitalizations increased, so did the number of IVAC+. Our goal was to investigate if there was a relationship between these two occurrences. Methods This was a retrospective study at the Audie Murphy VA Hospital (ALMVA) from October 2017 to December 2021. ALMVA is a level 1A facility with 232 beds and an active bone marrow transplant program in San Antonio, Texas. This study included acute care COVID-19 hospitalizations per 10,000 bed days of care and IVAC+ per 1000 ventilator days. Monthly acute and intensive care COVID-19 hospitalization rates were correlated with IVAC+ rates using Pearson correlation for the overall study period and in the subgroup of COVID pandemic months (Mar 2020-December 2021). Results During the overall study period, COVID-19 hospitalization rates were significantly associated with IVAC+ rates: acute care correlation 0.86 (p< 0.01) and intensive care correlation 0.33 (p=0.04). During the COVID-19 pandemic months, acute care COVID-19 hospitalizations but not intensive care COVID-19 hospitalizations, were correlated with IVAC+ (correlation 0.90, p< 0.01 and correlation 0.21, p=0.53, respectively). There were 0 IVAC+ before the pandemic months and this rose to 14 during (0 per 1000 ventilator days and 3.05 per 1000 ventilator days, respectively). All but 2 cases of IVAC+ had COVID-19. COVID-19 Hospitalizations and IVAC Plus, October 2017 to December 2021 A sharp increase in COVID-19 hospitalizations correlated with a rise in patients meeting criteria for IVAC Plus. Conclusion The natural history of COVID-19 disease has presented challenges for IVAC+ monitoring. COVID-19 can cause persistent fevers and worsening oxygenation, and antibiotic use is common during periods of clinical deterioration. These factors can fulfill criteria for IVAC+. In this study, each IVAC+ case was traced for safety bundle compliance. These bundles were followed, along with conservative fluid management, low tidal volume ventilation, and sedation breaks. Patients met NHSN criteria for IVAC+ despite these measures and most had COVID-19. Given the common occurrence of IVAC+ in COVID-19 patients, futures studies are needed to define if IVAC+ are preventable in this population and whether IVAC+ surveillance has any value among COVID-19 patients. Disclosures All Authors: No reported disclosures.

444. Effect of multidisciplinary management of CKD on proteinuria in people with HIV

Abstract Background Optimizing management of chronic kidney disease in people with HIV has become a more pressing priority both to minimize morbidity and preserve HIV antiretroviral options. Part of standard care is employing the beneficial effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) in patients with clinically significant proteinuria. Our analysis looks at the proteinuria outcomes of PWH with CKD co-managed by a multidisciplinary team of infectious disease and nephrology physicians nested in a Ryan White-funded clinic in New Orleans. Methods Patients with HIV and at least grade 3 CKD or with significant proteinuria were referred to the multidisciplinary clinic. Patients were evaluated by an HIV specialist and nephrologist at the initial visit for a jointly developed management plan. Renal function and proteinuria were measured at baseline and longitudinally per standard of care. Change in proteinuria and GFR over time were calculated. Patients were also assessed for whether they were prescribed ACE/ARB therapy, if appropriate. Patients included in this analysis were evaluated between January 1, 2021 and March 31, 2022. Results During the analysis period, 46 patients with at least CKD 3 or proteinuria were evaluated. 35 patients were Black non-Hispanic, 9 were White non-Hispanic, and 2 were Hispanic. 39 were male, and 7 were female. 35 had a previous diagnosis of hypertension, and 10 had diabetes mellitus. Of the 42 with a recorded baseline urine protein measurement, 24 were found to have clinically significant proteinuria. Of those with proteinuria, 16 were on an ACE or ARB at their baseline evaluation. 20 were on ACE/ARB’s the end of the analysis period (p=0.058). Average baseline proteinuria was 1,158 mg/g, while average final was 938 mg/g, which was less but not significantly different (p=0.54). Mean baseline GFR was not significantly different from final GFR (50.8 mL/min vs 50.5 mL/min, p=0.67). Conclusion A multidisciplinary model of managing CKD among people with HIV may improve adherence with management guidelines and limit progression of proteinuria and decrease in GFR. In general, the natural history of kidney disease with proteinuria is to worsen over time, so while not significant, proteinuria in this cohort did decrease over time Disclosures All Authors: No reported disclosures.

An ecological study regarding the association between paraquat exposure and end stage renal disease

BackgroundPersons who experience paraquat poisoning rapidly develop damage to a variety of organ systems including acute kidney injury (AKI), the occurrence of which is associated with an increased risk of death. However, little is known about the effects of chronic paraquat exposure on renal function and the onset of chronic renal disease. The objective of the current study is to assess the association between paraquat exposure and the incidence of end stage renal disease (ESRD) in the United States.MethodsData on the incidence of ESRD for the period 2010 through 2017 and kilograms of paraquat use per square mile for each county in the conterminous United States was obtained from the United States Renal Data System (USRDS) and the National Water Quality Assessment (NAWQA) Program, respectively. Negative binomial regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association between quartiles of paraquat exposure and the incidence of ESRD.ResultsThe incidence of ESRD increased with increasing paraquat density. Based on a 20-year exposure lag, those in the highest paraquat density quartile had a 21% higher rate of ESRD compared to the lowest quartile whereas for a 15-year lag the increase was 26%. Adjusted associations were attenuated though still followed an increasing linear trend across quintiles.ConclusionsThe results of this study are consistent with a large number of studies documenting a high incidence of AKI and a small number of studies chronic renal disease following acute and chronic paraquat exposure, respectively. While the pathophysiological mechanisms underlying kidney injury following paraquat poisoning are well understood, more research is necessary to understand the natural history of chronic kidney disease due to chronic paraquat exposure.

Descriptive Epidemiology of Hospitalization of Patients with a Rare Tumor in an Italian Region.

Rare tumors (RT) collectively account for one quarter of all malignancies in Italy. The low frequency and the large heterogeneity in natural history and outcome of individual diseases, together with a scarcity of epidemiological information make them a challenge for clinical practice, as well as for public healthcare organizations. We conducted a retrospective study to quantify the burden of hospitalization in a real-word setting in patients diagnosed with these diseases in an Italian region. RT patients were tracked along all hospital stays from 2000 to 2019 using hospital discharge records. Frequency of hospitalizations, average time spent in hospital and median timespan between consecutive admissions were considered. Re-hospitalization rates were analyzed through a multivariable negative binomial regression analysis to adjust for confounding and allowing for over-dispersion in count data. As a whole, 57,329 patients were identified at first stay for all studied tumors. A total of 183,959 admissions were retrieved, along a median of 3 hospitalizations per patient. Median timespan between hospitalizations shortened in the course of the study years (12.5 months in 2000-2004 to 5.4 months in 2015-2019). The overall re-hospitalization rate increased from 0.92 per patient/year (95% CI = 0.81-1.04) in 2000-2004 to 2.17 (95% CI = 1.90-2.47) in 2015-2019. Overall, the hospitalization rate of patients with a RT increased in the twenty years since the 2000 and particularly doubled starting from 2015. A higher burden of hospitalizations was found for tumors of the central nervous system, thoracic cavity, digestive tract and sarcomas. To the best of our knowledge this is the first paper related to access to Italian healthcare facilities of patients with these tumors.

An NMR-Based Model to Investigate the Metabolic Phenoreversion of COVID-19 Patients throughout a Longitudinal Study.

After SARS-CoV-2 infection, the molecular phenoreversion of the immunological response and its associated metabolic dysregulation are required for a full recovery of the patient. This process is patient-dependent due to the manifold possibilities induced by virus severity, its phylogenic evolution and the vaccination status of the population. We have here investigated the natural history of COVID-19 disease at the molecular level, characterizing the metabolic and immunological phenoreversion over time in large cohorts of hospitalized severe patients (n = 886) and non-hospitalized recovered patients that self-reported having passed the disease (n = 513). Non-hospitalized recovered patients do not show any metabolic fingerprint associated with the disease or immune alterations. Acute patients are characterized by the metabolic and lipidomic dysregulation that accompanies the exacerbated immunological response, resulting in a slow recovery time with a maximum probability of around 62 days. As a manifestation of the heterogeneity in the metabolic phenoreversion, age and severity become factors that modulate their normalization time which, in turn, correlates with changes in the atherogenesis-associated chemokine MCP-1. Our results are consistent with a model where the slow metabolic normalization in acute patients results in enhanced atherosclerotic risk, in line with the recent observation of an elevated number of cardiovascular episodes found in post-COVID-19 cohorts.

Ethnic differences in 25-year risk of incident chronic kidney disease among people with type 2 diabetes in New Zealand

IntroductionInsights into ethnic differences in the natural history of chronic kidney disease (CKD) among people with type 2 diabetes mellitus (T2DM) might inform clinical strategies to address disparities in hospitalization...

SA73 Addressing Unmet Needs of Patients With Neuronopathic Gaucher Disease Type 2 and Type 3: Creation of the GARDIAN Patient Registry

Gaucher Disease (GD) is a rare inherited metabolic disorder. Type 2 and Type 3 are neuronopathic and often result in infant death or progressive neurological deterioration. Current drug therapies do not cross the blood brain barrier and thus do not treat neuronopathic GD (nGD). GARDIAN data will generate real-world evidence on the natural history and impact of disease and will inform clinical trial design and healthcare decision making. The objective is to describe the development of a patient registry specific to nGD.