Faster Progression Research Articles

Abstract 15928: D-dimer as a New Biomarker of Aortic Stenosis Progression and Outcomes: Results From the PROGRESSA Study

Background: Aortic stenosis (AS) induces left ventricular (LV) remodeling and hypertrophy, which are key markers of the transition to heart failure. The present study aimed to evaluate the association between D-dimer plasma levels, LV hypertrophy and mortality with AS. Method: One-hundred and forty-six asymptomatic patients (mean age 65±13, men 76%) with mild or moderate AS prospectively recruited in the PROGRESSA study (NCT01679431) were included in this sub-analysis. All patients underwent Doppler-echocardiography annually to measure AS severity, LV mass indexed to body surface area (LVMi) and myocardial contraction fraction (MCF). The annualized changes in LVMi and MCF were calculated between baseline and last follow up. Results: Higher plasma levels of D-dimers at baseline were significantly associated with faster progression rate of LVMi and MCF (r 2 =0.18 and -0.22, respectively; all p<0.01). On multivariable analysis adjusted for age, sex, comorbidities, creatinine level, peak aortic jet velocity at baseline, D-dimers remained significantly associated with faster change in LVMi and MCF (all, p<0.01). Moreover, in multivariate analysis adjusted for age, sex, AS severity at baseline, higher levels of D-dimer were significantly associated with the progression to a higher grade of AS severity (HR [95% CI] 1.67 [1.14-2.46], p=0.009). During a median follow-up of 8.1 (5.6-9.9) years, 38 (26%) patients died. On multivariable Cox regression analysis, higher levels of D-dimer were associated with an increased risk of all-cause mortality (HR [95% CI]: 1.97 [0.98-1.97], p=0.05). Conclusion: Higher levels of D-dimer are associated with faster progression of AS severity, LV hypertrophy and dysfunction, and increased risk of mortality in patients with AS. This new blood biomarker may improve risk stratification and management of asymptomatic patients with AS. Further studies are needed to determine the mechanisms underlying this association between D-dimer and outcomes in AS.

Abstract 14926: Case of Severe Myocarditis Associated With Nivolumab-Relatlimab

Introduction: Immune checkpoint inhibitors (ICIs) are the standard of care for cancer but can cause immune-related adverse events (irAEs). Nivolumab/Relatlimab combination was approved in March 2022 for unresectable or metastatic melanoma. Cardiac toxicity associated with ICIs is rare but can be fatal. Prompt recognition is key. Description: We present a case of an 84-year-old with no cardiac history who experienced worsening fatigue a week after Nivolumab/Relatlimab infusion. This was followed by myalgia, double vision, shortness of breath, and chest heaviness. Her symptoms worsened, and she sought medical care. Tests showed elevated high-sensitivity troponin T and total creatine kinase levels of 1100 and 6000, respectively. Her first EKG revealed first degree AV block. Within hours, she developed a complete AV block. Her initial LVEF was 75%. She was diagnosed with “triple M" syndrome (myositis, myocarditis, and myasthenia) and received pulse-dose steroids and IV immunoglobulin. She developed myasthenic crisis with respiratory failure requiring intubation. Repeat echocardiogram revealed a drop in LVEF to 43% with new regional wall motion abnormalities attributed to worsening myocarditis. Considering fast progression and poor prognosis, the patient and her family chose comfort measures over escalation of care. Discussion: Myocarditis is a known but rare irAE with reported incidence of less than 1%. It can be associated with myositis and/or myasthenia. Clinical presentation varies, but rapidly progressive conduction disease is one of the most commonly described conditions. Direct T-cell cytotoxicity is the proposed mechanism. Cardiac irAEs can fully resolve if treated early. However, mortality remains elevated. Conclusion: This is one of the few reported cases of severe myocarditis from Nivolumab/Relatlimab. As the combination is still in phase IV development, more cases may emerge in the future and early recognition is vital.

Modelling Urban Green Spaces Depletion in Akure, Nigeria

The fast progress of urbanization and the accompanying dominance of concrete spaces over natural spaces are fundamental to current debates on urban planning and sustainable development in Nigeria and the world at large. It is worth noting that natural landscapes and greenery are critical to man's quality of life; yet, the majority of the population are going to reside in urban areas, to the detriment of urban green spaces, known as the "lungs of the city." A detailed account urban green spaces in Akure. Using Geographic Information System (GIS) and remote sensing techniques needs to be done. This study examines the status of urban green spaces in Akure, Nigeria to determine the rate of depletion and encroachment green spaces. The spatio-temporal analysis of green spaces in Akure was carried out between 1984 and 2022 using Supervised maximum likelihood classification procedure on Landsat 8 OLI/TIRS, Landsat 7 EMT+ and Landsat 4-5 TM Imageries. It took cognizance of attributes of vegetative cover at varying degrees such as Grasses and Shrubs, Light Vegetation, Secondary Vegetation, and Dense Vegetation. The rate of depletion of green areas, change statistic, socio-economic implication as well as planning implications were addressed. It is believed that assessing and analyzing its social, economic, and environmental impacts on urban inhabitants and their livelihoods would serve as a tool to educate and enlighten urban citizens about the need of including green space scheme into urban designs and planning in Akure.

Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study

The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the mechanisms remain unclear. The difficulty in elucidating the evolutionary origin of the earliest X4 viruses limits our understanding of this phenomenon. We tracked the evolution of the transmitted/founder (T/F) HIV-1 in RV217 participants identified in acute infection. The origin of the X4 viruses was elucidated by single genome amplification, deep sequencing and coreceptor assay. Mutations responsible for coreceptor switch were confirmed by mutagenesis. Viral susceptibility to neutralization was determined by neutralization assay. Virus CD4 subset preference was demonstrated by sequencing HIV-1 RNA in sorted CD4 subsets. We demonstrated that the earliest X4 viruses evolved de novo from the T/F strains. Strong X4 usage can be conferred by a single mutation. The mutations responsible for coreceptor switch can confer escape to neutralization and drive the X4 variants to replicate mainly in the central memory (CM) and naïve CD4 subsets. Likely due to the smaller viral burst size of the CM and naïve subsets, the X4 variants existed at low frequency in plasma. The origin of the X4 viruses preceded accelerated CD4 decline. All except one X4 virus identified in the current study lost the conserved V3 N301 glycan site. The findings demonstrate co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting which have implications for HIV-1 therapeutics and functional cure. The observations provide evidence that coreceptor switch can function as an evolutionary mechanism of immune evasion. Institute of Human Virology, National Institutes of Health, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Thai Red Cross AIDS Research Centre, Gilead Sciences, Merck, and ViiV Healthcare.

Abstract 051: Utilization of CT Perfusion to Optimize Selection Of Elderly Patients For Thrombectomy: A Retrospective analysis

Introduction CT perfusion (CTP) has been utilized to appropriately select patients with large vessel occlusion (LVO) for endovascular thrombectomy (EVT). Elderly patients and patients with fast‐growing ischemic cores have been shown to have worse outcomes after EVT. There is limited data on elderly patients aged ≥90 years old and ischemic core growth related to outcomes. We aimed to examine age, ischemic core growth, and outcomes in patients with LVO treated with EVT [1]. Methods This is a retrospective study using prospectively collected data from a large academic medical center. Patients with LVO and treated with EVT between December 2017 and December 2022 were included in this study. Patients without CTP completed prior to EVT, patients with missing baseline or 90‐day modified Rankin Scale scores (mRS), and patients in which CTP was completed but failed were excluded from this study. Early infarct growth rate (relative cerebral blood flow < 30% / last known well to CTP) was used to determine if ischemic core growth was fast (≥10ml/h) or slow (<10ml/h). We compared nonagenarians to younger patients (<90 years old) and examined outcomes. Primary outcome was 90‐day mRS, which we evaluated using a proportional odds ordinal regression model adjusted for baseline mRS, NIHSS, and confounding variables identified in univariate analyses. Secondary outcome was excellent reperfusion (TICI ≥2C), which was analyzed using hierarchical binomial logistic regression and adjusted for potential confounding variables. Subgroup analysis compared 90‐day mRS and reperfusion rates in octogenarians and nonagenarians [2]. Results Among 353 patients selected for EVT using CTP during the study, 325 patients were included in this study. Mean age ±SD was 74.61 ±14.49 years [133 (40.9%) ≥80 years old; 63 (19.4%) ≥90 years old] with initial NIHSS of 12 (IQR, 5 – 18) and 176 (54.2%) were female. Fewer nonagenarians selected for EVT with CTP were identified as fast progressors compared to younger patients, 7 (11.1%) compared to 65 (24.8%), respectively, Odds Ratio (OR) = 0.38 [95% Confidence Interval (CI), 0.16 – 0.87], p = 0.019. Nonagenarians who were fast progressors were more likely to experience worse 90‐day mRS (shift to next worse level) than younger patients and nonagenarians with slow progressing ischemic cores, median (IQR) mRS, 6 (5,6) versus 3 (1,6), adjusted OR (aOR) = 6.79 [95%CI, 1.14 – 40.29], p = 0.035. None of the nonagenarians with fast‐progressing ischemic cores achieved a 90‐day mRS of 0 – 2 or returned to baseline function. Patients aged ≥80 years, who were fast progressors, were more likely to shift to a worse 90‐day outcome than younger patients, aOR = 3.74 [95%CI, 1.43 – 9.75], p = .007. Comparable 90‐day mRS were found between octogenarians and nonagenarians, p = 0.55. Similar proportions of excellent reperfusion rates were seen in all patients, all p > 0.38. Conclusion Excellent reperfusion rates were not affected by age or ischemic core growth rate. Despite this, elderly patients with fast ischemic core growth were more likely to experience worse 90 day functional outcomes compared to younger patients and patients with slower core growth prior to EVT.

Sleep Quality is Associated with Axial Length Elongation in Myopic Children Receiving Orthokeratology: A Retrospective Study.

To identify potential demographic and lifestyle factors associated with progression of myopia with orthokeratology (ortho-k) treatment via follow-up of axial length (AL). In this retrospective observational study, demographics, ocular parameters, near-work distance, outdoor activities, and sleep quality were analyzed in 134 children with myopia aged 8~15 years using ortho-k and a follow-up for one year. Compared with the slow progression group, the participants in the fast progression group were younger in age (10.55 ±1.70 years vs 9.90 ±1.18 years, P = 0.009), demonstrated higher spherical equivalent (SE) value (-2.52 ±0.63 diopters (D) vs -3.05 ±0.89 D, P < 0.001), shorter near-work distance (P = 0.010), and poorer sleep quality (Pittsburgh sleep quality index [PSQI], 4.79 ±1.29 vs 3.81 ±1.38, P < 0.001) in the one-year follow-up. Furthermore, multivariate linear regression analyses showed that baseline age (B =-0.020, P = 0.020), SE (B = 0.0517, P < 0.001), and total PSQI (B=0.026, P = 0.001) were associated with axial elongation. Advanced logistic regression analyses demonstrated that shorter average near-work distance (P = 0.034), higher SE value (P = 0.023), and poorer sleep quality (P = 0.003) were associated with fast axial elongation. Sleep quality is one of the key factors associated with axial elongation in children with myopia after using ortho-k for one year. Further studies are required to confirm this observation and expand its practical applications.

Leadership, Education and Training for Youth in Contemporary African Union Programs

From September 16–19, 2022, the U.N. Secretary-General Antonio Guterres hosted the Transforming Education Summit at U.N. Headquarters in New York on the margins of the U.N. General Assembly. This summit mobilized stakeholders to act and collaborate in solidarity to find solutions for transforming education by 2030. This summit’s outcomes were national and international commitments to transform education with increased public engagement and support. Before the conference, the African Union had just concluded its fourth Specialized Technical Committee on Education, Science, and Technology with the theme of utilizing education, science, technology, and innovation to foster recovery in Africa and respond to, strengthen, and build resilience in a post-COVID-19 pandemic. At the same time, there was a need to enhance the response from the science, technology, and innovation sectors. Growing globalization and faster technological progress have created many new social, economic, environmental, and COVID-19 problems. Because of this, the Coalition on Media and Education for Development Africa Forum (CAFOR) and its partners have been looking at the needs and opportunities that come from these changes. CAFOR and its partners are also determined to look beyond Africa’s Continental Education Strategy (CESA 16–25) and examine how schools can prepare children in Africa for jobs and technologies that have yet to be created to solve future problems with innovation. CAFOR is forwardlooking and works towards building stronger partnerships on the continent, ensuring a shared responsibility to identify new opportunities and solutions.

L’eterogeneità del diabete autoimmune

Autoimmune diabetes is a heterogeneous disease, encompassing both type 1 diabetes, characterized by fast progression towards an insulin-dependent state, and latent autoimmune diabetes in adults (LADA), considered a less severe form of autoimmune diabetes with a mild metabolic decompensation. An extensive genetic, phenotypic, and humoral heterogeneity is recognized even within the group of people with LADA. In this review, we discuss the pathological and clinical heterogeneity of autoimmune diabetes, highlighting the current understanding and gaps in knowledge.

Elevated Liver Fibrosis Progression in Isolated PSC Patients and Increased Malignancy Risk in a PSC-IBD Cohort: A Retrospective Study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (CU), and rarely with Crohn's disease (CD). Various long-term analyses show different rates of cancer and the need for orthotopic liver transplantation (OLT) in patients with isolated PSC and with concomitant IBD, respectively. However, data on the detailed course of PSC with or without IBD are limited. We aimed to analyze the clinical disease course of PSC patients without IBD compared to PSC patients with UC and CD, respectively. A retrospective data analysis of patients with isolated PSC (n = 41) and of patients with concomitant IBD (n = 115) was performed. In detail, PSC disease characteristics including occurrence of dominant stenoses, liver cirrhosis, OLT and malignancy, as well as the temporal course of PSC activity and disease progression, were analyzed. A multivariable Cox regression model and a Fine-Gray competing risk model were further used for the independent risk factor analysis of cirrhosis development and OLT. Patients with isolated PSC were significantly older at first diagnosis than patients with PSC-IBD (39 vs. 28 years, p = 0.02). A detailed analysis of the course of PSC revealed a faster PSC progression after initial diagnosis in isolated PSC patients compared to PSC-IBD including significantly earlier diagnosis of dominant stenoses (29 vs. 74 months, p = 0.021) and faster progression to liver cirrhosis (38 vs. 103 months, p = 0.027). Patients with isolated PSC have a higher risk of developing cirrhosis than patients with PSC-IBD (Gray's test p = 0.03). OLT was more frequently performed in male patients with isolated PSC compared to males with coincident IBD (48% (n = 13) vs. 33% (n = 25), p = 0.003). Colorectal carcinoma was significantly more often diagnosed in patients with PSC-IBD than in isolated PSC (8.7% vs. 0%, p = 0.042). Patients with isolated PSC seem to have a different clinical course of disease than PSC patients with concomitant IBD characterized by a more pro-fibrotic disease course with earlier onset of liver cirrhosis and dominant stenosis but with less malignancy. These data may be interpreted as either a more progressive disease course of isolated PSC or a later diagnosis of the disease at an advanced disease stage. The different clinical courses of PSC and the underlying mechanisms of the gut-liver axis need further attention.

Fast Reconstruction of Microstructures with Ellipsoidal Inclusions Using Analytical Descriptors

Microstructure reconstruction is an important and emerging aspect of computational materials engineering and multiscale modeling and simulation. Despite extensive research and fast progress in the field, the application of descriptor-based reconstruction remains limited by computational resources. Common methods for increasing the computational feasibility of descriptor-based microstructure reconstruction lie in approximating the microstructure by simple geometrical shapes and by utilizing differentiable descriptors to enable gradient-based optimization. The present work combines these two ideas for structures composed of non-overlapping ellipsoidal inclusions such as magnetorheological elastomers. This requires to express the descriptors as a function of the microstructure parametrization. Deriving these relations leads to analytical solutions that further speed up the reconstruction procedure. Based on these descriptors, microstructure reconstruction is formulated as a multi-stage optimization procedure. The developed algorithm is validated by means of different numerical experiments and advantages and limitations are discussed in detail.

Disease survival and progression in TARDBP ALS patients from Sardinia, Italy.

Common genes implicated in amyotrophic lateral sclerosis (ALS) development may also influence its progression rate. The C9orf72 mutations featured a faster progression rate while the European SOD1 mutations were associated with a slower progression. In this study, we assessed the relationship between TARDBP and ALS progression/survival. ALS incident patients (2010-2019) were diagnosed by El Escorial revised criteria and staged over the disease course by the King's staging system. Disease progression was analysed by Kaplan-Meier survival curves and Cox regression models, with survival measured from symptom onset to death/tracheostomy or censor date. The study population included 76 patients carrying TARDBP mutations (A382T/G295S), 28 patients carrying the C9orf72 GGGGCC expansion, and 158 patients who had no evidence of causative genetic mutations (nmALS group). TARDBP patients reached death/tracheostomy later than C9orf72 and nmALS patients, independently of possible prognostic indicators (sex, age at ALS onset, diagnostic delay, phenotype at onset, and family history of ALS). On King's staging, the time elapsed between disease onset (King's stage 1) and involvement of the second body region (King's stage 2B) was similar in TARDBP and nmALS patients but longer in TARDBP than in C9orf72 patients. TARDBP patients reached King's stages 3 and 4 later than C9orf72 and nmALS patients. TARDBP patients have a better survival/prognosis than C9orf72-positive and nmALS patients. King's staging also suggested that the higher survival rate and the slower progression associated with the TARDBP mutation could mainly be attributed to the longer time elapsed between King's stages 2B to 3.

Factors affecting progression of non-Alzheimer dementia: a retrospective analysis with long-term follow-up.

Non-Alzheimer's dementias, including vascular dementia (VaD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and Parkinson's disease dementia (PDD), possess unique characteristics and prognostic factors that remain poorly understood. This study aims to investigate the temporal course of these subtypes and identify the impact of functional, neuropsychiatric, and comorbid medical conditions on prognosis. Additionally, the relationship between hippocampal atrophy, white matter intensities, and disease progression will be examined, along with the identification of key covariates influencing slow or fast progression in non-Alzheimer's dementias. A total of 196 patients with non-Alzheimer's dementias who underwent at least three comprehensive evaluations were included, with proportions of VaD, FTD, LBD, and PDD being 50, 19.39, 19.90, and 10.71%, respectively. Patient demographics, comorbidities, neuropsychiatric and neuroimaging parameters, and global evaluation were analyzed using appropriate statistical methods. The study followed patients for a mean duration of 62.57 ± 33.45 months (ranging from 11 to 198 months). The results from three different visits for each non-AD dementia case demonstrated significant differences in various measures across visits, including functional capacity (BDLAS), cognition (MMSE), and other neuropsychological tests. Notably, certain genotypes and hippocampal atrophy grades were more prevalent in specific subtypes. The results indicate that Fazekas grading and hippocampal atrophy were significant predictors of disease progression, while epilepsy, extrapyramidal symptoms, thyroid dysfunction, coronary artery disease, diabetes mellitus, hypertension, stroke, hyperlipidemia, sleep disorders, smoking, and family history of dementia were not significant predictors. BDLAS and EDLAS scores at the first and second visits showed significant associations with disease progression, while scores at the third visit did not. Group-based trajectory analysis revealed that non-AD cases separated into two reliable subgroups with slow/fast prognosis, showing high reliability (Entropy = 0.790, 51.8 vs. 48.2%). This study provides valuable insights into the temporal course and prognostic factors of non-Alzheimer's dementias. The findings underscore the importance of considering functional, neuropsychological, and comorbid medical conditions in understanding disease progression. The significant associations between hippocampal atrophy, white matter intensities, and prognosis highlight potential avenues for further research and therapeutic interventions.

MRI-based multivariate gray matter volumetric distance for predicting motor symptom progression in Parkinson's disease

While Parkinson's disease (PD)-related neurodegeneration is associated with structural changes in the brain, conventional magnetic resonance imaging (MRI) has proven less effective for clinical diagnosis due to its inability to reliably identify subtle changes early in the disease course. In this study, we aimed to develop a structural MRI-based biomarker to predict the rate of progression of motor symptoms in the early stages of PD. The study included 88 patients with PD and 120 healthy controls from the Parkinson's Progression Markers Initiative database; MRI at baseline and motor symptom scores assessed using the MDS-UPDRS-III at two time points (baseline and 48 months) were selected. Group-level volumetric analyses at baseline were not associated with the decline in motor functioning. Then, we developed a patient-specific multivariate gray matter volumetric distance and demonstrated that it could significantly predict changes in motor symptom scores (P < 0.05). Further, we classified patients as relatively slower and faster progressors with 89% accuracy using a support vector machine classifier. Thus, we identified a promising structural MRI-based biomarker for predicting the rate of progression of motor symptoms and classifying patients based on motor symptom severity.

KEAP1/NRF2 Mutations in Stem Cells Define an Aggressive Subset of Head and Neck Cancer Patients Who Have a Poor Prognosis, Lung Metastasis, and Therapeutic Failure.

Mutations in Keap1/Nrf2 in head and neck cancer result in abnormal cell growth. Progenitor cells, bulk tumor cells, and head and neck cancer stem cells (HN-CSCs) may all harbor these mutations. Nevertheless, whether Keap1/Nrf2 mutations in HN-CSCs have an impact on clinical outcomes is unknown. Cancerous HN-CSCs and benign stem cells were obtained from freshly resected head and neck cancer patients (n = 50) via flow cytometry cell sorting and tested for Keap1/Nrf2 mutations. The existence of Keap1/Nrf2 mutations in HN-CSCs, as well as their correlations with tumor mutations, pathologic tumor stage, tumor histologic grades, lung metastasis, treatment outcomes, and the patient's age and conditions, are assessed at the last follow-up visit. Thirteen tumors were found to have Keap1/Nrf2 mutations in their HN-CSCs. More than half of the lung metastases and disease progression occurred in HN-CSCs with mutations. Patients whose tumors carried Keap1/Nrf2 mutations in their HN-CSCs had significantly shorter progression-free survival, overall survival, and time of treatment failure than their non-HN-CSC counterparts. These associations were partly driven by HN-CSCs, in which Keap1/Nrf2 mutations were overrepresented in fast progressors and associated with an increased risk of disease progression. Our findings suggest that molecular genotyping of HN-CSCs may facilitate personalized treatment strategies and assist in identifying patients who are likely to benefit from chemotherapy.

The Impact of Infections on the Progression of Chronic Kidney Disease.

Background and Objective: Infectious diseases continue to be a global burden and their impact is even worse if the patients already have other comorbidities. Because chronic kidney disease is very frequent, affecting 10% of the population, our study aims to explore the impact that infectious events have on its progression. Material and Methods: This is a retrospective, observational study based on a cohort of 238 dialyzed patients from the Nephrology Clinic of "Dr. Carol Davila" Clinical Hospital of Nephrology, Bucharest, who were followed from their first visit for five years, between 1 January 2007 and 1 January 2022. For each of them, the presence of an infectious event and the moment of the initiation of dialysis were recorded. Results: Statistical analysis showed that the patients who had at least one infectious episode were older (p = 0.004), their hemoglobin and lymphocytes were significantly lower (p = 0.03 and p = 0.02, respectively) and the time until the initiation of dialysis was lower (p = 0.007). Also, the preservation of kidney function was influenced by the number and the severity of infectious episodes. In the univariate Cox model, the following variables were associated with increased risk of dialysis: advanced age (p: 0.009; HR: 1.021; CI: 1.005 to 1.036), low hemoglobin (p: 0.001; HR: 0.861; CI: 0.786 to 0.943), previous diagnosis of chronic obstructive pulmonary disease (p: 0.002; HR: 2.467; CI: 1.376 to 4.424), presence of hematuria (p: 0.03; HR: 1.604; CI: 1.047 to 2.457) and increased values of proteinuria (p: 0.01; HR: 1.122; CI: 1.028 to 1.224) and of serum creatinine measured both at the time of the first visit and at the time of each infectious event (p: <0.001; HR: 1.262; CI: 1.141 to 1.396). Also, the presence of an infectious episode was associated with a 1.7-fold increase in the risk of dialysis initiation. The independent predictors of survival identified by the multivariate Cox model were age (p: 0.004; HR: 1.034; CI: 1.010-1.058), serum creatinine (p: <0.001; HR: 1.421; CI: 1.203 to 1.658) and proteinuria (p: <0.001; HR: 1.241; CI: 1.126 to 1.369) at the time of enrollment, but also the presence of an infectious episode during the patient's evolution (p: 0.04; HR: 1.705; CI: 1.013 to 2.868). Conclusions: In the evolution of patients with chronic kidney disease, an active search for individual factors favoring the occurrence of infectious episodes should be taken into consideration to prevent a faster progression toward end-stage kidney disease.

Cellular insights of beech leaf disease reveal abnormal ectopic cell division of symptomatic interveinal leaf areas.

The beech leaf disease nematode, Litylenchus crenatae subsp. mccannii, is recognized as a newly emergent nematode species that causes beech leaf disease (BLD) in beech trees (Fagus spp.) in North America. Changes of leaf morphology before emergence from the bud induced by BLD can provoke dramatic effects on the leaf architecture and consequently to tree performance and development. The initial symptoms of BLD appear as dark green, interveinal banding patterns of the leaf. Despite the fast progression of this disease, the cellular mechanisms leading to the formation of such aberrant leaf phenotype remains totally unknown. To understand the cellular basis of BLD, we employed several types of microscopy to provide an exhaustive characterization of nematode-infected buds and leaves. Histological sections revealed a dramatic cell change composition of these nematode-infected tissues. Diseased bud scale cells were typically hypertrophied and showed a high variability of size. Moreover, while altered cell division had no influence on leaf organogenesis, induction of cell proliferation on young leaf primordia led to a dramatic change in cell layer architecture. Hyperplasia and hypertrophy of the different leaf cell layers, coupled with an abnormal proliferation of chloroplasts especially in the mesophyll cell layers, resulted in the typical interveinal leaf banding. These discrepancies in leaf cell structure were depicted by an abnormal rate of cellular division of the leaf interveinal areas infected by the nematode, promoting significant increase of cell size and leaf thickness. The formation of symptomatic BLD leaves is therefore orchestrated by distinct cellular processes, to enhance the value of these feeding sites and to improve their nutrition status for the nematode. Our findings thus uncover relevant cellular events and provide a structural framework to understand this important disease.

Clinical long-term outcome of hepatitis D compared to hepatitis B monoinfection

Background and aimsHepatitis D virus (HDV) infection causes the most severe form of chronic viral hepatitis. However, it is still unclear to what extent the underlying cirrhosis may contribute to disease progression. The aim of this study was to compare the long-term outcome of HDV infection with HBV monoinfection in a single-center cohort of both non-cirrhotic and cirrhotic patients.MethodWe retrospectively studied 175 patients with chronic hepatitis D (CHD) who were followed for at least 6 months (median of 6.3 (0.6–23.6) years). In addition, we selected 175 patients with HBV monoinfection (CHB) who were matched for gender, age, region of origin, HBeAg status, and bilirubin. Liver-related clinical end points were defined as hepatic decompensation (ascites, encephalopathy, variceal bleeding), liver transplantation, HCC, or liver-related death.ResultsClinical complications developed earlier (4.6 vs. 6.2 years) and more frequently (35.4% vs. 12.6%, p < 0.01) in CHD patients. In a multivariate Cox regression, HDV infection was independently associated with the development of end points (p < 0.01; HR: 3.0; 95% CI 1.4–6.4). However, in cirrhotic patients there were no significant differences between HBV and HDV in the development of end points. Besides, CHB patients with cirrhosis developed more frequently HCC (35.5%) than CHD patients with cirrhosis (18.5%).ConclusionOur results confirmed that HDV leads to a faster progression to cirrhosis compared to HBV. However, once cirrhosis is present, not HDV but the underlying cirrhosis is the dominate intrinsic risk factor for the development of liver-related end points and for the progression to HCC.

Re-thinking strategic myopia: A necessary condition analysis of heuristic and firm's performance

At times of fast paced technology progress and global disruptions strategic myopia can be particularly harmful to firms. A narrow view of actors, events and tendencies is a firm's environment, combined with short-term preferences is widely recognized in the literature as leading to belated or inadequate responses to challenges. Manager's myopia is typically portrayed as a systematic bias, inducing underperformance. However, empirical evidence is more than nuanced in this respect. In this study, we view strategic myopia as an effective heuristic triggered in uncertain environments and specific task conditions. We use the necessary condition analysis (NCA) to examine the association between strategic myopia and firm performance through a necessity logic lens. This innovative method provides insights into the relationship between low levels of strategic myopia dimensions and firm performance in both the short- and long term. We measure strategic myopia and firm performance as multidimensional constructs on a representative sample of 658 Polish managers. Our results challenge the conventional wisdom that low strategic myopia is necessary for high performance. We highlight the nuanced role of myopia across its dimensions (i.e., competitive, cooperative, temporal, and learning) and shed light on its implications for both short- and long-term performance.

Аваскулярный некроз головки бедренной кости — излечение возможно!

INTRODUCTION: Avascular necrosis of the femoral head (ANFH) is a severe type of pathology among degenerative and dystrophic diseases of the hip joint (DDHD) characterized by fast progression. It affects mainly males of the work-able age (20 to 50 years old) and accounts for up to 4.7% of DDHD cases. In short time, it leads to loss of the normal joint anatomy and disability. The article shows the results of long-term follow up of a patient diagnosed with the initial pre-radiological stage of ANFH who was underwent bilateral (33 years and 38 years) revascularization surgery of the femoral head and neck using the inferior epigastric artery along with a concomitant veins and muscular distal cuff. The positive result of the surgical intervention was confirmed clinically (an intact range of motion in the affected joints as well as the absence of pain), and due to Computer Tomography (visualization of artificial intraosseous canals done surgically as well as the preserved shape of the femoral head). CONCLUSION: Taking into account the widely used non-invasive current diagnostic methods like Thermal Imaging, Magnetic Resonance Imaging and Computer Tomography, revealing the pre-radiological stage avascular necrosis of the femoral head now is not a difficult task. The proposed surgical procedure with transposition of the vascular complex into the femoral neck and head helps to maintain the viability of the bone and avoid joint replacement.

Credible Pathways to Catching Up with Climate Goals in Nigeria

This paper seeks to address Nigeria’s challenges in meeting its climate objectives by investigating feasible pathways that can be implemented to accelerate progress and ensure credibility in meeting these targets. By examining the current policies and practices in place as well as successful strategies employed by other countries, this paper aims to provide strategies and policy implications recommendations for Nigeria to enhance its climate action efforts. The potential scenarios developed in this study ranged from increasing renewable energy capacity to implementing stricter regulations and standards for industries to reduce their carbon footprint, promote sustainable production processes, and strengthen climate governance and policy frameworks. The authors further investigated these measures and discovered that implementing stricter regulations and standards for industries would reduce their carbon footprint, promote sustainable production processes, and strengthen climate governance and policy frameworks. As such, Nigeria will be able to meet its climate goals more quickly as a result of the following factors: preventing environmental degradation, funding environmentally friendly infrastructure, and improving public transportation systems that can reduce vehicle-related greenhouse gas emissions. The authors developed policy measures based on the proposed twelve credible pathways to catching up with climate goals in Nigeria, thereby promoting faster progress by the Nigerian government in achieving climate goals. By adopting these measures, Nigeria’s progress toward the proposed zero net by 2060 will be significantly accelerated. It will position Nigeria as a continental leader in sustainable development and contribute to the overall global efforts to mitigate climate change. This will not only benefit the environment but also lead to financial development and an improved standard of living for its citizens.