Rate Of Progression Research Articles

Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice.

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively.Using 16S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability.Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels.Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.

Venous disease progression in western Europe (VENPRO): A prospective cohort study.

Objective: A prospective cohort study aimed to determine factors which influence the progression of chronic venous disease (CVD) in an attempt to aid in the early identification of those at patients who are likely to benefit from early intervention.Methods: A prospective cohort study of patients referred to tertiary vascular services with varicose veins over 7years was conducted. The primary outcome measure was the rate of disease progression from time of referral to time of consultation. The secondary outcome measure was to the rate of venous complications during the same time period.Results: 1000 patients from routine varicose vein waiting lists were included in the study. The mean waiting time was 2.96 ± 1.25years. The majority of patients were female (73% versus 27%), and the average age was 57.8 ± 14.7years. One fifth of the cohort developed a complication or showed evidence of disease progression. Logistic regression showed that advancing age and previous episodes of cellulitis are significant risk factors for the development of CVD progression.Conclusions: Varicose veins are more than a cosmetic issue and can be associated with substantial health and economic costs. Continuous identification of risk factors will enable clinicians to implement treatment strategies earlier for at risk patients.

Primary Prevention Strategy for Non-Communicable Diseases (NCDs) and Their Risk Factors: The Role of Intestinal Microbiota

Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients’ lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1

Factors influencing the cost-effectiveness of radiofrequency ablation for Barrett's esophagus with low-grade dysplasia in Australia.

Endoscopic eradication therapy using radiofrequency ablation (RFA) is considered an acceptable alternative to surveillance monitoring for Barrett's esophagus with low-grade dysplasia (LGD). This study aimed to estimate whether RFA for LGD is cost-effective and to determine which factors influence cost-effectiveness. A Markov model was developed to estimate the incremental cost per quality-adjusted life year (QALY) gained for RFA compared with endoscopic surveillance. An Australian longitudinal cohort study (PROBE-NET) provides the basis of the model. Replacing surveillance with RFA yields 10 fewer cases of HGD and 9 fewer esophageal adenocarcinoma (EAC)-related deaths per 1000 patients' treatment, given on average 0.192 QALYs at an additional cost of AU$9211 (€5689; US$6262) per patient (incremental cost-effectiveness ratio AU$47,815 per QALY). The model is sensitive to the rate of EAC from LGD health state, the utility values, and the number of RFA sessions. Hence, the incremental benefit ranges from 0.080 QALYs to 0.198 QALYs leading to uncertainty in the cost-effectiveness estimates. When the cancerous progression rate of LGD falls <0.47% per annum, the cost-effectiveness of RFA becomes questionable. RFA treatment of LGD provides significantly better clinical outcomes than surveillance. The additional cost of RFA is acceptable if the LGD to EAC rate is >0.47% per annum and no more than three RFA treatment sessions are provided. Accurate estimates of the risk of developing EAC in patients with LGD are needed to validate the analyses.

Characterisation of incident interstitial lung disease in late systemic sclerosis.

Interstitial lung disease (ILD) is a common and potentially lethal complication of systemic sclerosis (SSc). Screening by HRCT is recommended in all patients with risk factors, including early disease. Little is known on late presentations of ILD. This study aimed to characterize the incidence, risk factors and outcomes of late-onset SSc-ILD. Subjects enrolled in the Canadian Scleroderma Research Group (CSRG) cohort from 2004 to 2020 without prevalent ILD were included. Incidence and risk factors for ILD (on HRCT) were compared according to disease duration above (late) and below (earlier) 7 years from first non-Raynaud manifestation. Risk of ILD progression was compared using Kaplan-Meier and multivariable Cox models. Overall, 199/969 (21%) patients developed incident ILD over a median of 2.4 [1.2, 4.3] years. The incidence rate in late SSc (3.7/100 person-years) was lower than in earlier SSc (relative risk 0.68, 95%CI:0.51-0.92). Risk factors for incident ILD included male sex, diffuse subtype, myositis, anti-topoisomerase I autoantibodies and higher C-reactive protein levels. Patients with late-onset ILD were also less frequently White and more frequently had arthritis and anti-RNA-polymerase III autoantibodies. Lung disease severity was similar between late- and earlier-onset SSc-ILD (FVC 88% and 87%, DLCO 64% and 62%, respectively). Progression rates were also similar between late- and earlier-onset SSc-ILD (log-rank p=0.8, hazard ratio 1.11, 95% CI: 0.58-2.10). ILD can present in late SSc. Risk factors and progression rates overlapped with earlier-onset SSc-ILD. Surveillance for ILD should continue in longstanding SSc. Frequency and modality of monitoring remain to be defined.

Electricity Bill Savings from Reduced Household Energy Consumption in Apartment Complexes

Apartments account for 64.6% of all housing units in the Republic of Korea, and most of them receive electricity under a contract, which includes a progressive rate plan. Recently, due to the electrification of energy used in homes and the growing adoption of electric vehicles, electricity consumption in apartment complexes has been gradually increasing. Given the characteristics of the progressive rate system, an increase in electricity usage results in a significant higher rise in electricity bills. Thus, an effective alternative is required to reduce electricity bills for each household. In this paper, the savings in electricity bills achieved by reducing household electricity usage are analyzed from both apartment complex and individual household perspectives, using metering data from 13,332 households. When households are sorted by the amount of savings in descending order, the resulting values are found to follow a negative exponential curve. This indicates that the benefits from reducing electricity usage in households with higher saving are significantly larger compared to other ones. We analyzed bill savings when electricity usage reductions were selectively applied to the top 10%, 20%, and 30% of households with the largest savings. From the results, it is found that the largest savings in electricity bills for households are achieved when usage reductions are applied to the top 10% of households. It is expected that this amount of savings would encourage these households to reduce their electricity consumption. Additionally, it is found that the savings for apartment complexes and the total savings for selected households are not the same, resulting in changes in the bills for households that do not reduce their usage. From the results, it was observed that when the usage reduction of selected households is small or the proportion of households reducing usage is low, the common area charges for non-reducing households tend to increase, leading to higher electricity bills. On the contrary, when the usage reduction of selected households is large or the proportion of households reducing usage is high, the common area charges for non-reducing households tend to decrease, resulting in lower electricity bills.

Mathematical modeling and analysis of the co-dynamics of crime and drug abuse

This study explores the dynamics of crime and substance abuse within a population by developing a novel mathematical model that integrates social interactions, rehabilitation efforts, and relapse probabilities. The model introduces a critical metric, the control reproduction number \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$(\\mathscr{R}_j)$$\\end{document}, to quantify the invasion threshold for these behaviors. The findings reveal that the crime/substance-free equilibrium is globally asymptotically stable when \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathscr {R}_j\\le 1$$\\end{document}. At the same time, entrenched equilibria become stable where \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathscr {R}_j >1$$\\end{document}. Additionally, the model predicts the potential for a co-existent equilibrium where crime/substance abuse and a free state can coexist if all reproduction numbers exceed unity. Sensitivity analysis identifies key factors influencing \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathscr {R}_j$$\\end{document}, including behavioral transmission, internal progression rates, intervention efficacy, and recovery/relapse probabilities. Numerical simulations validate theoretical predictions regarding the stability of different equilibria, highlighting the critical importance of interventions targeting transmission reduction and rehabilitation efficiency. The research underscores the significance of understanding invasion dynamics for the coexistence of behaviors. It demonstrates the utility of mathematical modeling in elucidating the spread of social phenomena and informing effective control strategies.

Modern views on pathogenesis of cognitive impairment in patients with type 2 diabetes mellitus

Currently, the features of the pathogenesis of cognitive impairment in patients with diabetes mellitus are being actively studied. The study of the mutual influence of these pathologies is of particular relevant not only in connection with a decrease in cognitive functions in patients with diabetes mellitus, but also due to the fact that the management of diabetes mellitus requires a thorough approach to the implementation of doctor’s recommendations and self-control on the part of the patient himself. The degree of cognitive impairment has a direct impact on patient compliance and, consequently, on the management and control of the disease. A comprehensive strategy is necessary for the prevention and progression of cognitive impairments in patients with diabetes mellitus. This strategy should include minimizing modifiable risk factors, controlling comorbidities, maintaining a healthy lifestyle, following a diet, engaging in regular physical activity, and medication therapy. Also, one of the key aspects is the control of blood glucose levels. Regular monitoring and maintaining a stable level of sugar can significantly reduce the risk of developing cognitive impairments in diabetic patients. This review also analyzes the effects of oral hypoglycemic drugs, incretin-based therapy and insulin on the risk of developing cognitive impairments. This review examines important aspects of the role of pathogenetic links and clinical manifestations of type 2 diabetes mellitus in the development of cognitive impairment and the possibility of influencing their development and rate of progression. Understanding these relationships will help develop effective strategies for the prevention and treatment of cognitive impairments in patients with diabetes mellitus.

Surgical and Oncological Outcomes of Level III-IV Versus Level I-II Inferior Vena Cava Thrombectomy: A Decennial Experience of a High-Volume European Referral Center.

In patients with renal cell carcinoma (RCC) the role of the extent of tumor thrombus into the inferior vena cava (IVC) has never been addressed from a surgical and oncologic standpoint. This study aims to evaluate differences between level III-IV versus level I-II patients concerning peri- and postoperative morbidity, additional treatments and long-term oncological outcomes. Overall, 40 patients with RCC underwent radical nephrectomy (RN) with IVC thrombectomy at a single European institution between 2010 and 2023. Complications were reported according to the European Union (EAU) guidelines recommendations. Spider chart served as graphical depiction of surgical and oncologic outcomes. Overall, 22 (55%) and 18 (45%) patients harbored level III-IV and I-II IVC thrombus. Level III-IV patients experienced significantly higher rates of intraoperative transfusions (68 vs 39%), but not significantly higher rates of intraoperative complications (32% vs 28%). Level III-IV patients had significantly higher rates of postoperative transfusions (82% vs 33%) and Clavien Dindo ≥3 complications (41% vs 15%). In level III-IV versus level I-II patients, median follow up was 482 and 1070 days, the rate of distant recurrence was 59% and 50%, the rate of systemic progression was 27% and 13%, and the rate of additional treatment/s was 64% and 61%, respectively (all p values > 0.05). Overall survival was 36% in level III-IV patients and 67% in level I-II (p = 0.001). Our findings suggest that patients with level III-IV RCC who are candidates for IVC thrombectomy should be counselled about the higher likelihood of postoperative severe adverse events and worse overall survival relative to level I-II counterparts.

High-Energy Transsyndesmotic Ankle Fracture Dislocation-Does Deltoid Ligament Repair Influence the Progression of Posttraumatic Arthritis in Logsplitter Injuries?

To determine the effect of deltoid ligament repair on the development of posttraumatic arthritis in logsplitter ankle injuries. Retrospective cohort. Academic, Level I trauma center. Patients ≥18 years of age with logsplitter injuries (OTA/AO 44B, 44C) treated with open reduction internal fixation (ORIF) with or without deltoid ligament repair from January 2008 to October 2021. The rate of posttraumatic arthritis (PTOA) development at the final follow-up (minimum 6 months) after ORIF was evaluated using the Kellgren-Lawrence scale. The achievement of acceptable reduction indicated by articular reduction <2 mm, and a medial clear space ≤4 mm was assessed at 6 weeks postoperatively with weight-bearing radiographs. The effect of deltoid ligament repair on the development of PTOA was investigated. Fifty-nine patients aged 49.1 ± 17.2 years met inclusion criteria with a mean follow-up of 16.6 months (range = 6 to 96). Twenty-six of 59 patients (44%) had developed PTOA at the final follow-up. Acceptable reduction was achieved in 83.1% (49/59) of fractures. The acceptable reduction rate in fractures undergoing deltoid ligament repair was 100% versus 78% in those without deltoid ligament repair (13/13 vs. 36/46, P = 0.017). The rate of PTOA development was significantly lower in patients who underwent deltoid ligament repair (15%) than those who did not (52%), P = 0.026. Patients who underwent deltoid ligament repair had a significantly reduced rate of PTOA development leading to arthrodesis compared with those who did not (0% vs. 17%, P = 0.013). Logsplitter injuries resulted in a high rate of development of posttraumatic arthritis. An acceptable reduction is required to minimize the risk of development of PTOA and progression to arthrodesis. Deltoid ligament repair during ORIF may facilitate acceptable reduction and decrease the rate of PTOA and progression to arthrodesis in these injuries. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Ascending aortic length predicts adverse outcomes in type a intramural hematoma.

Ascending aortic length has recently been recognized as a novel predictor of adverse events in aortic diseases, but its prognostic value in type A intramural haematoma is unknown. We aimed to evaluate the association between ascending aortic length and outcomes in patients with type A intramural haematoma initially managed medically. We retrospectively analyzed patients with acute type A intramural haematoma. Ascending aortic length was measured by computed tomography. The primary outcome was aortic progression, defined as aortic intervention or aortic-related death. A total of 98 patients were enrolled. During a median follow-up of 2.6 years, aortic progression occurred in 27 patients (27.6%), ie, 9 events per 100 patient-years). Patients with ascending aortic length ≥11 cm had significantly higher rates of aortic progression (54.2% [20.9 events per 100 patient-years] vs 18.9% [6.1 events per 100 patient-years], p = 0.001), surgical intervention (45.8% vs 12.2%, p = 0.001), and presence of ulcer-like projection (25.0% vs 2.7%, p = 0.002) compared to those with ascending aortic length <11 cm. Kaplan-Meier analysis demonstrated lower progression-free survival in the ascending aortic length ≥11 cm group (p = 0.0021). Ascending aortic length had a sensitivity of 61.9% and specificity of 77.8% for predicting aortic progression, with an area under the curve of 0.756 (95% confidence interval: 0.649-0.862). Ascending aortic elongation may identify a high-risk subgroup of acute type A intramural haematoma patients initially managed medically who could potentially benefit from early surgery. Ascending aortic length should be considered in the risk stratification and management of these patients.

Association between dietary patterns and the prognosis of amyotrophic lateral sclerosis in China: a cross-sectional study

BackgroundRecently, a growing number of studies have specifically examined the impact of dietary variables on the development and progression of amyotrophic lateral sclerosis (ALS). The purpose of this study was to investigate the correlation between different dietary patterns and Chinese ALS patients’ prognosis.MethodsA retrospective study was conducted by recruiting 590 patients with ALS who attended and were regularly followed at hospitals in Nanjing from 2016 to 2023. Nutrient intake was calculated using dietary information collected through the food frequency questionnaire (FFQ), and patients were divided into a control group and special diet groups, including a high-calorie group (HC), a high-protein group (HP), and a ketogenic diet group (KD), based on their specific intake. And used the Kaplan-Meier product limiting distribution to compare the time required to transition between phases of different dietary patterns and to estimate cumulative survival probabilities.ResultsPatients in the HP had a better nutritional status. And the disease progression rate (ΔFS) was significantly associated with dietary patterns, with the KD group having the lowest ΔFS. Meanwhile, special diets extended the survival time of stage 4 patients but had no effect on the overall survival of the disease.ConclusionA special diet can be one of effective options for patients with advanced ALS. Patients with poor nutritional status may choose the HP diet, whereas those with underlying conditions should consider the ketogenic diet with caution.

Revisiting PD: Unraveling the brain-first and body-first perspectives

Parkinson’s disease (PD) has undergone significant advancements in diagnosis and treatment over the past century, with apparent dopaminergic cell degeneration on dopamine transporter scans and a strong response to medication being key features. However, the etiology remains complex, involving various pathogenic mechanisms beyond alpha-synuclein accumulation. The recent brain-first versus body-first hypothesis, emerging from advances in functional imaging and clinical symptom clustering, suggests distinct starting points of alpha-synuclein pathology-either in the brain or the body, with subsequent spread via neural connections. This theory, exemplified by the alpha-synuclein origin site and connectome (SOC) model, proposes that body-first PD may originate in the enteric nervous system and spread to the brain, while brain-first PD starts within the central nervous system, such as the olfactory bulb or amygdala. While the SOC model offers valuable insights into the progression of PD, it raises several controversies. Critics argue that the model may oversimplify the disease’s complexity, failing to account for overlapping symptoms and the varying progression rates observed in different subtypes. Furthermore, there are concerns about the lack of longitudinal data and the potential for reclassification of PD subtypes over time. Despite these challenges, the ongoing development of imaging techniques that reflect in-vivo pathology holds promise for resolving these controversies and advancing the selection of patients for disease-modifying therapies.

IMPACT OF PRE-EXISTING HYPERTENSION ON THE DEVELOPMENT AND OUTCOMES OF PERIPARTUM CARDIOMYOPATHY

An uncommon but dangerous heart ailment known as peripartum cardiomyopathy (PPCM) may develop in the last month of pregnancy or during the first five months after giving birth. It has been shown that pre-existing hypertension is one risk factor that might make PPCM more severe. The purpose of this research is to assess how pre-existing hypertension affects the course, clinical manifestation, and results of PPCM. Objective: To evaluate the impact that pre-existing hypertension has on the clinical course, echocardiographic results, and maternal outcomes in PPCM maternal cases. Methods: At the DHQ Hospital KDA, Kohat, a retrospective cohort study was carried out between September 2023 and August 2024. There were 56 women with PPCM in total; 28 of them had pre-existing hypertension and the other 28 did not. Data on demographics, clinical conditions, and echocardiograms were gathered. The two groups' maternal outcomes—heart failure progression, recovery of left ventricular function, and problems after childbirth—were compared. SPSS version 26 was used for data analysis, and a p-value of less than 0.05 was deemed statistically significant. Results: Comparing women with pre-existing hypertension to the non-hypertensive group, they showed considerably higher rates of heart failure progression (39% against 21%, p = 0.04) and significantly lower left ventricular ejection fraction (LVEF) at diagnosis (30.1% versus 35.5%, p = 0.01). Women with hypertension were more likely to have persistent LVEF impairment (36% vs 18%, p = 0.03). Additionally, the group with hypertension saw higher readmission rates (25% vs 10.7%, p = 0.02). Conclusion: A substantial risk factor for unfavourable outcomes in PPCM, such as reduced heart function and increased rates of postpartum problems, is pre-existing hypertension. Improving PPCM results for hypertensive women requires closer observation and focused care.

Study on the causes and coping strategies of adolescent mental illness

In recent years, especially since the epidemic, there has been an explosive increase in the incidence of adolescent mental disorders, which has aroused the attention of the whole society. From the perspectives of evolution, humanism, and psychodynamics, this paper analyzes the deep-rooted causes of the increasing incidence of psychological disorders in adolescents and explores various dilemmas adolescents face. From an evolutionary point of view, the current rate of social progress exceeds the rate of human evolution and the rate of cognitive improvement of young people, making it difficult for young people to adapt to complex social environments. In humanitarian terms, excessive academic pressure places a heavy burden on young people. From the perspective of psychodynamics, the conflict between standard, ego, and superego can cause mental illness in adolescents. In addition, this paper points out that adolescent mental illness marks the evolution of social awareness of mental health, and all parties in society need to build a supportive policy framework to foster widespread awareness of mental health.

Evaluating CRMS/CFSPID phenotypes and outcomes: A retrospective study from a large UK cystic fibrosis centre

BackgroundCystic fibrosis transmembrane conductance regulator metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID) is a designation given following a positive newborn screen for cystic fibrosis (CF) when CF is not excluded but cannot be confirmed. We describe the long-term clinical outcomes of a CRMS/CFSPID cohort. MethodsA retrospective, single centre study of children with a current or previous diagnosis of CRMS/CFSPID. Study period extended from February 1, 2007 to August 1, 2022. Baseline and longitudinal data were assessed. Results30 children were designated as CRMS/CFSPID between 2007 and 2021. At baseline, 13 CFTR variants were identified, of which F508del and R117H 7T/9T were most common (occurring in 25 and 20 children respectively). Initial mean immunoreactive trypsinogen and sweat chloride were 82.8 mmol/L and 34.3 mmol/L respectively. During longitudinal assessment (n = 27), occurring over a mean duration of 8.5 years, five children progressed to CF at a mean age of 9.5 years. All children were pancreatic sufficient except one who reclassified to CF. Four isolated Pseudomonas aeruginosa and 12 isolated Staphylococcus aureus, of which one and two progressed to CF respectively. All recent Z-scores for weight and spirometry were above −2. Initial mean sweat chloride was higher in those who progressed to CF versus those who did not, although this did not reach statistical significance (38.4 mmol/L versus 32.0 mmol/L respectively, p = 0.105). ConclusionsMost children with CRMS/CFSPID remained well with a low progression rate to CF. This supports a less intensive medical surveillance approach. Our results highlight the importance of assessment in a dedicated CRMS/CFSPID clinic during adolescence to detect progression to CF after 6 years of age.

Long-term Effect of the HCV Elimination With Direct-acting Antivirals on the Progression of Gastroesophageal Varices.

Gastroesophageal varices (GEV) hemorrhage is a serious complication that can lead to unfavorable outcomes in cirrhotic patients. However, the clinical impact of HCV elimination [sustained viral response (SVR)] by direct-acting antivirals (DAAs), particularly on the long-term effects on the endoscopic findings of GEV have not been sufficiently evaluated. This study aimed to investigate whether HCV elimination with DAA treatment suppresses the progression of GEV. The clinical courses of the endoscopic findings of GEV were retrospectively compared between patients without an SVR (non-SVR group: n=71) and those who achieved an SVR with DAAs (DAA-SVR group: n=38). At 1, 3, 5, and 7 years, the cumulative GEV progression rates were 8.7%, 32.8%, 45.6%, and 66.2%, respectively. At 3 years, the cumulative GEV progression rate in the DAA-SVR group was similar to that in the non-SVR group. Beyond 3 years, cases with GEV progression were found in the non-SVR group, but not in the DAA-SVR group. At 7 years, the cumulative GEV progression rate in the DAA-SVR group was significantly lower than that in the non-SVR group (p<0.05, log-rank test). Variceal hemorrhage occurred in eight patients in the non-SVR group, while no bleeding events were observed in the DAA-SVR group during the observational period [8/71 (11.3%) vs. 0/38 (0.0%), p<0.05]. DAA treatment suppresses the progression of GEV over the long term.

Identification of Resistance to &amp;lt;i&amp;gt;Puccinia striiformisf&amp;lt;/i&amp;gt;. sp. &amp;lt;i&amp;gt;tritici&amp;lt;/i&amp;gt; (&amp;lt;i&amp;gt;Pst&amp;lt;/i&amp;gt;) in Some Commercial and Elite Bread Wheat Lines

Stripe rust is caused by &amp;lt;i&amp;gt;Puccinia striiformisf&amp;lt;/i&amp;gt;. sp. &amp;lt;i&amp;gt;tritici&amp;lt;/i&amp;gt; (&amp;lt;i&amp;gt;Pst&amp;lt;/i&amp;gt;) threatening wheat production in Ethiopia. The emerged virulent stripe rust races at one point of the world spread to the rest of wheat-producing countries by the wind as well as human travels and damaged popular resistant wheat cultivars thereby posing food insecurity. However, wheat cultivars succumb to new Pst race (s) soon after their release from research centers. This study aimed to determine stripe rust resistance in some Ethiopian commercial and elite bread wheat lines. In 2017, a total of 37 commercial and elite bread wheat lines were exposed to stripe rust in under the disease hot spot areas (Kulumsa and Meraro) Arsi zone Oromia regional state. In the second year (2018), 22 promising lines consisting of 16 commercial bread wheat and 6 elite’s lines were evaluated both at seedling and adult plant growth stages. The seedling test was conducted in the greenhouse at Kulumsa research center using three Pst races. In field evaluations, terminal severity (TRS), coefficient of infection (CI), area under disease progress curve (AUDPC), disease progress rate (DPR), and spike infection (SI) were considered. Of the 37 commercial and elite bread wheat lines, 19 (51.4%) exhibited lower or equal disease reaction compared to the resistant check (Enjoy) across locations and seasons. Eleven bread wheat lines showed both adult plant and seedling resistance. The 37 commercial wheat lines that showed field resistance was further exposed to three Pst races at the seedling stage and 11 exhibited seedling resistance to all races. This study has identified seedling and adult plant resistance in some commercial and elite bread wheat lines to the prevailing Pst races.

2D Echocardiographic aortic root dimensions and longitudinal analysis with artificial intelligence using an open dataset from a UK-wide collaborative

Abstract Background Surveillance of aortic dimensions requires reproducible measurements, and knowledge of the rate of progression in those with dilatation. Purpose To develop an open machine-learning method for measuring the aortic root and proximal ascending aorta on echocardiograms, validate it through a multi-expert panel from the Unity UK Echocardiography AI Collaborative, and applying the AI to derive the rate of progression in historical databases. Methods The neural network was trained on 1478 parasternal long-axis images. Each image was labelled with key points for the aortic annulus, sinus and sinotubular junction, and proximal ascending aorta dimensions. Labels accommodated inner-to-inner and leading-to-leading conventions. For validation, the end-diastolic and mid-systolic images were identified (accommodating different guidelines recommendations) from 100 studies, and 10 expert echocardiographers made the aortic measurements. The consensus of experts defined the reference standard, and the variation between individual experts defined the acceptable variation for the AI. The AI was then applied to 724 echocardiograms of 102 patients under surveillance spanning 12 years (ranging from 4 to 17 scans per patient) without intervention. Training data labels and networks are made freely available on our project website. Results The median absolute deviations between the AI and the expert consensus ranged from 0.06cm to 0.17cm across the 16 measurements. For the individual expert opinions this was from 0.08cm to 0.19cm. For 7/16 measurements, there was no statistically significant difference between the AI deviation and the individual-expert deviation. The AI’s confidence level was a useful indicator of the reliability of the AI measure. For the top 9 deciles of AI confidence level, the AI measurements had significantly smaller deviations than the individual experts. The rates of progression averaged across the three aortic measurements was 2.0 mm/decade (95% CI 1.0 to 3.0; p =0.007). Conclusion Expert consensus can be used to both define the reference standard and also the range of acceptable deviation from consensus. Overall, the AI performs similarly to experts and more importantly, provides an automated estimate of confidence. The validated AI is consistent over time, and when applied retrospectively to patients with dilated aortic roots, found the rate of progression was more rapid than in previously reported healthy patients. This approach could be applied generally in developing medical AI to not only make reproducible measurements but to automate large scale longitudinal studies with little input, and ultimately serves as a useful research and clinical tool.Figure: AI(red) vs Expert (blue)Table: AIDeviations from Consensus

Effectiveness of Implant Therapy in Patients With and Without a History of Periodontitis: A Systematic Review With Meta-Analysis of Prospective Cohort Studies.

This systematic review investigates the effectiveness of implant therapy in patients with and without a history of periodontitis in terms of implant loss, peri-implant marginal bone loss (MBL), and occurrence of peri-implant diseases. The protocol of the present meta-analysis was registered on PROSPERO (CRD42021264980). An electronic search was conducted up to April 2024. All prospective cohort studies reporting implant loss, MBL, and occurrence of peri-implant diseases in both patients with a history of periodontitis (HP) and patients with no history of periodontitis (NHP) after at least 36-month follow-up were included. The risk of bias was evaluated using the Newcastle-Ottawa Scale and the quality of the evidence was also assessed. A meta-analysis was performed on the selected outcomes at the available follow-up time points. Subgroup analyses were conducted based on follow-up time, rate of progression and severity of periodontitis, and implant surface characteristics. Publication bias was evaluated using the Funnel plot and Egger's test. From 13 761 initial records, 14 studies (17 articles) were finally included. Eight studies had a low risk of bias level, and six had a medium risk of bias level. Meta-analysis showed that HP patients had a significantly greater risk for implant loss (HR: 1.75; 95% CI: 1.28-2.40; p = 0.0005; I2 = 0%), MBL (MD: 0.41 mm; 95% CI 0.19, 0.63; p = 0.0002; I2 = 54%), and peri-implantitis (3.24; 95% CI: 1.58-6.64; p = 0.001; I2 = 57%) compared to NHP, whereas no significant intergroup difference for peri-implant mucositis was found. Subgroup analyses revealed a particularly greater risk for implant loss for HP patients over a ≥ 10-year follow-up (HR: 2.02; 95% CI: 1.06-3.85; p = 0.03; I2 = 0%) and for patients with a history of grade C (formerly aggressive) periodontitis (HR: 6.16; 95% CI: 2.53-15.01; p < 0.0001; I2 = 0%). A greater risk for implant loss for stages III-IV (severe) periodontitis, and implants with rough surfaces was also found. Within the limits of heterogeneous case definitions and methods of assessment, a history of periodontitis has been proved to significantly increase the risk for implant loss, particularly at long follow-up (≥ 10 years) and in case of rapidly progressive forms (grade C), and for MBL and peri-implantitis.