Severe Stages Of Disease Research Articles

Male breast cancer: a 32-year retrospective analysis in radiation therapy referral center in northern Iran

Background: Breast cancer commonly occurs in women, and male breast cancer makes up less than 1% of all cases of breast cancer. The limited prevalence of male breast cancer has led to decreased attention being paid to this condition, resulting in its diagnosis occurring at later ages and at more severe disease stages. Objectives: This study evaluates the demographic and clinicopathological characteristics of male patients diagnosed with breast cancer who visited the northern region of Iran from 1992 to 2023. Methods: This descriptive study reviewed data from 58 cases of male breast cancer between 1992 and 2023. The study aimed to examine and describe the information connected to these patients. The data were analyzed with SPSS.22 set at P value less than 0.05. Results: The mean age of the patients examined was 62.10±13.40 years, while their mean BMI was 27.08±4.95. The study found no statistically significant correlation between BMI with stage and kinds of recurrence, including metastasis and local recurrence (P>0.05). The right and left breast involvement rates were equal (48.28%) in 28 cases, and 2 cases (3.40%) had bilateral involvement. The bone was the predominant site of metastasis, accounting for 69.23% of cases. The analysis revealed no significant correlation between stage and metastasis (P=1.000) or local recurrence (P=0.543). Most metastasis and all the local recurrence were observed in stages 3 and 4. Conclusion: Male breast cancer mainly occurs in older age and is diagnosed in the advanced stages of the disease. Therefore, it is recommended to inform men and develop suitable screening programs, especially in high-risk families.

Valvular heart disease and cardiomyopathy in China: epidemiology and current treatments.

The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China. In connection with the previous section, this ninth section of the report offers a comprehensive analysis of valvular heart disease and cardiomyopathy. Although rheumatic valve disease is still the main cause of valvular heart disease in China, with the aging of the population and the improvement of living standards, the prevalence of degenerative valvular heart disease is on the rise. Because many patients with valvular heart disease have only mild to moderate valve stenosis or insufficiency, and no symptoms, the detection rate in the population is low and late, resulting in many patients been in the severe late stage of disease at visit, increasing the difficulty of treatment and affecting effectiveness and prognosis. Therefore, we should strengthen the examination and screening of valvular heart disease in order to find and prevent it as early as possible. In addition, compared with other diseases, the treatment of valvular heart disease needs more and higher technical support (surgery, intervention, etc). However, not all hospitals can provide relevant technologies. At present, the treatment of valvular heart disease is still mainly concentrated in the provincial hospitals. It is necessary to carry out more professional training so that more doctors and hospitals can participate in the treatment of valvular heart disease. Cardiomyopathy is a group of myocardial diseases with abnormal myocardial structure and/or function, but couldn't be explained by hypertension, coronary atherosclerosis, valvular heart disease and congenital heart disease. It includes hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic cardiomyopathy (also known as arrhythmogenic right ventricular cardiomyopathy), restrictive cardiomyopathy (RCM) and undifferentiated cardiomyopathy.

The application of cell products for the treatment of critical limb ischemia in patients with diabetes mellitus: a review of the literature

The number of patients with diabetes mellitus (DM) has been progressively increasing worldwide over the past decades, and many international organizations consider DM as a public health emergency of the 21st century.Critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease (PAD) in DM and is characterized by a high risk of limb loss without revascularization. Traditional treatment tactics include open and endovascular revascularization surgical techniques. However, in patients not eligible for revascularization and in cases where performed surgical treatment performed has been ineffective, there are almost no therapeutic alternatives, often leading to amputations and death. As of today, one of the newest non-surgical treatment options is cell therapy. Among different cells, mesenchymal stromal cells (MSCs) are potentially one of the most prospective for use in this patient population.This article provides an overview of clinical trials using cell therapy in patients with CLI.To analyze publications, electronic databases PubMed, SCOPUS, ClinicalTrials, and ScienceDirect were searched to identify published data from clinical trials, research studies, and review articles on cell therapy for critical lower extremity ischemia. After the search, 489 results were received.As a result of systematic selection, 22 clinical trials were analyzed.According to the analyzed literature data, the use of cell products in this category of patients is effective and safe. Cell therapy can stimulate the formation of new vessels and enhances collateral circulation; it is also reported improved distal perfusion, increased pain-free walking distance, decreased amputation rates, and increased survival rates.Nevertheless, further study of the potential use of this category of drugs is needed.

Comprehensive analysis of hyperspectral features for monitoring canopy maize leaf spot disease

Accurate quantification of hyperspectral features altered by plant disease infection is pivotal for effective disease management. However, the sensitivity of hyperspectral features to plant disease progression remains elusive, primarily because these features are often influenced by plant growth and environmental factors in addition to the specific disease. This study explores the sensitivity of biophysical and spectral features as indicators for maize adaptation to leaf spot disease. Using high-resolution UAV hyperspectral imaging, we captured maize adaptation dynamics over 30 days post-infection. We evaluated the sensitivity and importance of hyperspectral features for disease monitoring, including biophysical parameters retrieved by the PROSAIL model, and spectral features, including spectral reflectance, vegetation indices (VIs), and wavelet features (WFs). Our findings reveal that WFs first indicate disease response as early as 6 days after infection (DAI), followed by VIs at DAI 8, and variations in chlorophyll content (Cab) become apparent by DAI 10. The Cab, plant senescence reflectance index (PSRI), and normalized photosynthetic reflectance index (NPRI) are determined to be important features at the early stage of the disease. Our experimental results show that the different feature sets are complementary at the early and severe stages of the disease. Our classification models integrating Cab, VIs, and WFs showed higher overall accuracy than models using only spectral features or VIs, with a maximum improvement of 9.36 %. However, these feature sets are redundant in the mild and initial severe disease stages, where models using only spectral features achieve the highest overall accuracy of 86.21 %. This study underscores the novel insights by offering an understanding of plant responses to disease infection and enhancing early detection strategies.

Benzyloxychalcone Hybrids as Prospective Acetylcholinesterase Inhibitors against Alzheimer's Disease: Rational Design, Synthesis, In Silico ADMET Prediction, QSAR, Molecular Docking, DFT, and Molecular Dynamic Simulation Studies.

Acetylcholinesterase inhibitors (AChEIs) are crucial therapeutic targets for both the early and severe stages of Alzheimer's disease (AD). Chalcones and their chromone-based derivatives are well-known building blocks with anti-Alzheimer properties. This study synthesized 4-benzyloxychalcone derivatives and characterized their structures using IR, 1H NMR, 13C NMR, and HRMS. Additionally, the synthesized 4-benzyloxychalcone derivatives were tested for anti-acetylcholinesterase (AChE) activity. The synthesized compounds outperformed galantamine, which is used as a positive control against acetylcholinesterase. Utilizing an acetylcholinesterase (AChE) receptor (PDB ID: 4EY7)-chalcone derivative (12a-c), a molecular docking investigation was performed on the synthesized compounds. The goal was to predict the binding sites and energies of the derivatives with respect to the receptor amino acids. The dynamic behavior of the ligand-receptor complex resulting from the interaction of the best docking compounds 12a and 12c with the acetylcholinesterase receptor was used to analyze the stability via MD simulation. MM/GBSA and MM/PBSA were used to calculate free binding energies using snapshots from system trajectories. Advanced computational approaches incorporating long-range corrections were utilized to calculate the molecular characteristics of chalcone derivatives 12a-c at the DFT/wB97XD/6-311++G(d,p) level. We used the molecular electrostatic surface potential (MESP) with high-quality data and visualization to find the most active site in these molecules. Reactivity descriptors, including the condensed Fukui function, chemical hardness (η), dual descriptors, chemical potential (μ), and electrophilicity (ω), were calculated for the chalcone derivatives.

Race-modified estimated glomerular filtration rate underestimates chronic kidney disease prevalence in Black patients undergoing partial and radical nephrectomy: Implications for surgical planning.

In estimated glomerular filtration rate equations (eGFR), the race multiplier (RM) yields greater eGFR values and may assign less severe chronic kidney disease (CKD) stages to black individuals. When deciding on appropriateness for partial nephrectomy (PN), patients with CKD are often considered a relative or absolute indication. We hypothesize that the eGFR RM may have ramifications for patients being counseled for radical nephrectomy (RN) versus PN to manage their renal tumor. We utilized prospective and retrospective, IRB-approved single-center databases to select patients who underwent PN or RN between 2016 and 2022. Demographics, preoperative risk factors, preoperative eGFR, and surgical management were collected. Descriptive statistics and two-tailed difference of proportion tests compared the percentage of patients with CKD who underwent nephrectomy. This cohort included 1137 patients who underwent RN or PN, including 74 (6.5%) Black patients and 93.5% (n = 1063) non-Black patients. There was no statistically significant difference between the eGFR of Black and non-Black individuals using the Modification of Diet in Renal Disease equation (P = 0.24) or Chronic Kidney Disease Epidemiology Collaboration 2009 (CKD-EPI 2009) (P = 0.45); however, there was statistically significant difference in eGFR between sample populations when using CKD-EPI 2021 (P = 0.0055). Of the Black patient cohort, 16.2% of patients reclassified to a worse CKD class using CKD-EPI 2021, including 9.5% of Black patients reclassified to CKD3a or worse, and 14.6% of all patients (Black and non-Black) reclassified to a different CKD class under the CKD-EPI 2021 equation. There are quantitative differences in the evaluation of eGFR when utilizing different equations that may impact clinical considerations and health equity outcomes for nephrectomy across racial groups.

Deregulated immune cell recruitment orchestrated by c-MET impairs pulmonary inflammation and fibrosis

BackgroundPulmonary fibrosis (PF) represents the pathologic end stage of several interstitial lung diseases (ILDs) associated with high morbidity and mortality rates. However, current treatments can only delay disease progression rather than provide a cure. The role of inflammation in PF progression is well-established, but new insights into immune regulation are fundamental for developing more efficient therapies. c-MET signaling has been implicated in the migratory capacity and effector functions of immune cells. Nevertheless, the role of this signaling pathway in the context of PF-associated lung diseases remains unexplored.MethodsTo determine the influence of c-MET in immune cells in the progression of pulmonary fibrosis, we used a conditional deletion of c-Met in immune cells. To induce pulmonary fibrosis mice were administered with bleomycin (BLM) intratracheally. Over the course of 21 days, mice were assessed for weight change, and after euthanasia at different timepoints, bronchoalveolar lavage fluid cells and lung tissue were assessed for inflammation and fibrosis. Furthermore, c-MET expression was assessed in cryobiopsy sections, bronchoalveolar lavage fluid cells samples and single cell RNA-sequencing dataset from human patients with distinct interstitial lung diseases.Resultsc-MET expression was induced in lung immune cells, specifically in T cells, interstitial macrophages, and neutrophils, during the inflammatory phase of BLM-induced PF mouse model. Deletion of c-Met in immune cells correlated with earlier weight recovery and improved survival of BLM-treated mice. Moreover, the deletion of c-Met in immune cells was associated with early recruitment of the immune cell populations, normally found to express c-MET, leading to a subsequent attenuation of the cytotoxic and proinflammatory environment. Consequently, the less extensive inflammatory response, possibly coupled with tissue repair, culminated in less exacerbated fibrotic lesions. Furthermore, c-MET expression was up-regulated in lung T cells from patients with fibrosing ILD, suggesting a potential involvement of c-MET in the development of fibrosing disease.ConclusionsThese results highlight the critical contribution of c-MET signaling in immune cells to their enhanced uncontrolled recruitment and activation toward a proinflammatory and profibrotic phenotype, leading to the exacerbation of lung injury and consequent development of fibrosis.

Prevalence Estimation of Dementia/Alzheimer’s Disease Using Health and Retirement Study Database in the United States

BackgroundUpdated prevalence estimates along the continuum of Alzheimer’s disease (AD) can foster a more nuanced and effective approach to managing AD within the current healthcare landscape.ObjectivesThis study aims to estimate the prevalence and severity distribution of dementia/AD (including mild, moderate, and severe stages) and all-cause mild cognitive impairment (MCI) in the United States using data from the Health and Retirement Study (HRS).DesignRetrospective study.SettingData from the bi-annual HRS surveys involving in-depth interviews of a representative sample of Americans aged >50 years.ParticipantsDementia/AD and all-cause MCI patients from the 4 most recent HRS surveys (2014, 2016, 2018 and 2020).MeasurementsAD was identified based on diagnosis (self-report). Cognitive performance (modified Telephone Interview of Cognitive Status [TICS-m]) scores in the dementia/AD range were also captured; all-cause MCI was similarly identified using the TICS-m. Dementia/AD and MCI prevalence, as well as the distribution by dementia/AD stage (mild, moderate, or severe), were estimated. Sampling weights developed by HRS were applied to ensure the sample’s representativeness of the target population and unbiased estimates for population parameters.ResultsAcross the four HRS surveys, the total number of HRS respondents ranged from 15,000 to 21,000 (unweighted); 7,000 to 14,000 had TICS-m scores. The estimated prevalence of AD (all severity categories combined) in the 2014, 2016, 2018, and 2020 HRS surveys was 1.2%, 1.2%, 1.3% and 1.0%, respectively using the diagnosis-based approach; using the cognitive performance-based approach, 23–27% patients had scores in the dementia/AD ranges across the 4 surveys. The estimated prevalence of all-cause MCI was consistently 23% in each survey. In the 2020 survey, the distribution of mild, moderate, and severe disease stages was 34%, 45%, and 21%, respectively, in patients self-reporting an AD diagnosis, and 55%, 40%, and 5%, respectively in all patients meeting TICS-m threshold for dementia/AD.ConclusionThe prevalence of AD diagnosis based on self-report was approximately 1% across the 4 most recent HRS surveys and may reflect the proportion of patients who have actively sought healthcare for AD. Among HRS survey respondents with cognitive scores available, over 20% were in the dementia/AD range. The distribution of disease by stage differed for self-reported AD diagnosis vs dementia/AD based on cognitive scores. Discordance in estimates of dementia/AD and stage distributions underscores a need for better understanding of clinical practice patterns in AD diagnosis, use of clinical assessment tools, and severity classification in the United States. Accurate patient identification is needed, especially early in the AD disease continuum, to allow for timely and appropriate initiation of new anti-amyloid treatments.

Substitutions of saturated fat intakes with other macronutrients and foods and risk of NAFLD cirrhosis and all-cause hepatocellular carcinoma: a prospective cohort study

BackgroundShort-term trials have shown a reduction in liver fat when saturated fatty acids (SFAs) are substituted with polyunsaturated fatty acids (PUFA), or with low-glycemic carbohydrates. However, few cohort studies have been conducted to investigate the associations of replacing SFA and SFA-rich foods with different macronutrients and foods in more severe stages of liver disease; nonalcoholic fatty liver disease (NAFLD) cirrhosis and hepatocellular carcinoma (HCC). ObjectivesTo investigate associations between the substitution of SFA and SFA-rich foods with other macronutrients and foods and NAFLD cirrhosis and HCC in a middle-aged to elderly Swedish population of n = 77,059 males and females. MethodsTime-to-event analyses were performed to investigate associations between the food and macronutrient substitutions and NAFLD cirrhosis and HCC. Multivariable Cox regression models were constructed to estimate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Statistical isocaloric and equal-mass substitutions were performed using the leave-one-out method. Prespecified nutrient and food substitutions of interest were SFA with carbohydrates, SFA with fiber, SFA with PUFA, butter with margarine and vegetable oils, unprocessed red meat with fish, and milk with fermented milk. ResultsOver a median follow-up of 24 y, 566 cases of NAFLD cirrhosis and 205 cases of HCC were registered. Overall, dietary substitutions showed no clear associations with either NAFLD cirrhosis or HCC. Substituting SFA with carbohydrates showed an HR of 0.87 (95% CI: 0.74, 1.02) for HCC and 1.00 (95% CI: 0.89, 1.11) for NAFLD cirrhosis. Substituting milk with fermented milk showed an HR of 0.93 (95% CI: 0.85, 1.01) for HCC and 0.97 (95% CI: 0.92, 1.03) for NAFLD cirrhosis. ConclusionsNo clear associations were observed between diet and NAFLD cirrhosis or HCC. Although accompanied by low precision, possible lowered risks of HCC by substituting SFA with carbohydrates or milk with fermented milk might be of interest, but needs replication in other cohorts.

Alterations in Cerebrospinal Fluid Urea Occur in Late Manifest Huntington's Disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and postmortem tissues of HD patients. However, the relationship between disease course and urea elevations, along with the molecular mechanisms responsible for these disturbances remain unknown. To better understand the molecular disturbances and timing of urea cycle metabolism across different stages in HD. We completed a global metabolomic profile of cerebrospinal fluid (CSF) from individuals who were at several stages of disease: pre-manifest (PRE), manifest (MAN), and late manifest (LATE) HD participants, and compared to controls. Approximately 500 metabolites were significantly altered in PRE participants compared to controls, although no significant differences in CSF urea or urea metabolites were observed. CSF urea was significantly elevated in LATE participants only. There were no changes in the urea metabolites citrulline, ornithine, and arginine. Overall, our study confirms that CSF elevations occur late in the HD course, and these changes may reflect accumulating deficits in cellular energy metabolism.

Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta-analysis.

Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta-analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD)=3.62, 95% confidence interval (CI) (2.88, 4.35), P<0.00001] and stroke volume [MD=6.59, 95% CI (3.22, 9.96), P=0.0001] and significantly reduced left ventricular end-systolic volume [standard mean difference (SMD)=-0.52, 95% CI (-0.67, -0.37), P<0.00001], left ventricular end-diastolic volume index [SMD=-1.24, 95% CI (-1.61, -0.86), P<0.00001], and left ventricular end-systolic volume index [SMD=-1.06, 95% CI (-1.43, -0.70), P<0.00001]. In terms of biomarkers, levosimendan significantly reduced the level of brain natriuretic peptide [SMD=-1.08, 95% CI (-1.60, -0.56), P<0.0001], N-terminal pro-brain natriuretic peptide [SMD=-0.99, 95% CI (-1.41, -0.56), P<0.00001], and interleukin-6 [SMD=-0.61, 95% CI (-0.86, -0.35), P<0.00001]. Meanwhile, levosimendan may increase the incidence of hypotension [risk ratio (RR)=1.24, 95% CI (1.12, 1.39), P<0.0001], hypokalaemia [RR=1.57, 95% CI (1.08, 2.28), P=0.02], headache [RR=1.89, 95% CI (1.50, 2.39), P<0.00001], atrial fibrillation [RR=1.31, 95% CI (1.12, 1.52), P=0.0005], and premature ventricular complexes [RR=1.86, 95% CI (1.27, 2.72), P=0.001]. In addition, levosimendan reduced all-cause mortality [RR=0.83, 95% CI (0.74, 0.94), P=0.002]. In conclusion, our study found that levosimendan might reverse ventricular remodelling when applied in patients with left ventricular systolic dysfunction, especially in patients undergoing cardiac surgery, decompensated heart failure, and septic shock.

Outcomes Following Surgical Fixation of Upper Extremity Fractures in Patients with Chronic Kidney Disease

Moderate to severe (stage III-IV) chronic kidney disease (CKD) and end stage renal disease (ESRD) have been shown to be independent risk factors for sustaining a fragility fracture. High rates of complications and mortality are associated with fracture fixation in patients with CKD, but existing literature is limited. It is unknown how CKD stage III-IV or ESRD affects outcomes in upper-extremity fractures. We hypothesize that patients with CKD stage III-IV or ESRD will have high complication rates after surgical fixation of upper extremity fractures. We identified all patients between 2008 and 2018 who underwent operative fixation of an upper extremity fracture proximal to the distal radius with a diagnosis of CKD stage III-IV or ESRD at the time of injury. Those with an acute kidney injury at the time of injury or a history of a kidney transplant were excluded. Demographics, medical complications, and surgical complications were collected retrospectively. Data on readmissions within 90 days and mortality within 1 year were also collected. Thirty-five patients were identified. Three patients had ESRD. Fractures included two clavicle, twelve proximal humerus, one humeral shaft, ten distal humerus, five olecranon, two ulnar shaft, one radial shaft, and two both-bone forearm fractures. In total, 91.4% of fractures were closed injuries. Surgical complications occurred in 40% of patients. The reoperation rate was 11.4%, and all cases of reoperation involved hardware removal. The all-cause 90-day readmission rate was 34.3%. The 1-year mortality rate was 8.6%. Surgical complications occurred in 40% of patients with CKD stage III-IV or ESRD who underwent fixation for an upper extremity fracture. It is important to counsel these patients regarding their high risk for complications. Further research is needed to investigate and identify how to mitigate risk. Prognostic IV.

Impact of prior use of antiplatelets on COVID-19 susceptibility, progression, and severity: a population-based study

Introduction and objectivesHypercoagulability and thromboembolism are processes that arise from severe acute respiratory syndrome coronavirus 2 infection and are responsible for a high degree of coronavirus disease 2019 (COVID-19)-related morbidity and mortality. This study sought to assess the effect of antiplatelet drugs on COVID-19 severity (risk of hospitalization and mortality), susceptibility to severe acute respiratory syndrome coronavirus 2 infection, and progression to severe COVID-19. MethodsWe conducted a population-based case-control study in a northwestern region of Spain in 2020. The study involved 3060 participants with a positive polymerase chain reaction test who were hospitalized, 26 757 participants with a positive polymerase chain reaction test who were not hospitalized, and 56 785 healthy controls. ResultsTriflusal seemed to be associated with a significant increase in risk of hospitalization (aOR, 1.97; 95%CI, 1.27-3.04) and susceptibility to infection (OR, 1.45; 95%CI, 1.07-1.96). It also appeared to lead to a nonsignificant increase in the risk of mortality (OR, 2.23; 95%CI, 0.89-5.55) and/or progression to more severe disease stages (OR, 1.42; 95%CI, 0.8-2.51). Aspirin seemed to be associated with a statistically significant decrease in susceptibility to severe acute respiratory syndrome coronavirus 2 infection (OR, 0.92; 95%CI, 0.86-0.98). ConclusionsTriflusal use appears to increase the risk of susceptibility to COVID-19 infection and an even higher risk of hospitalization, whereas the other antiplatelets could be associated with a reduction in the risk of the various outcomes or have no effect on risk. These findings could support reconsideration of triflusal prescription in COVID-19 pandemic situations.

Association of plasma lactoferrin levels with disease severity in glaucoma patients.

To explore the relationship between plasma lactoferrin (Lf) and glaucoma, assessing the clinical utility of Lf in glaucoma. A cross-sectional study involved 161 glaucoma patients and 115 healthy controls, with a follow-up of 14 subjects after approximately 2 years. Plasma Lf markers were quantified using ELISA, comparing levels between glaucoma patients and healthy controls, and analyzing plasma Lf across different glaucoma severity grades. Glaucoma patients had significantly elevated plasma Lf levels compared to healthy controls (p < 0.001). Higher plasma Lf levels correlated with more severe disease stages (HPA grades showed ρ = 0.435, p < 0.001; AGIS grades showed ρ = 0.436, p < 0.001) and reduced retinal nerve fiber layer (RNFL) thickness (RNFL thickness showed ρ = -0.204, p = 0.024). ROC curve analysis demonstrated the efficacy of glaucoma markers in differentiating early-stage from advanced glaucoma. Plasma Lf levels are significantly associated with glaucoma severity and may be involved in the pathogenic progression of the disease.

Analysis Of Hospital Data on Angioplasty and Infrainguinal Bypass for Chronic Critical Ischemia of The Lower Limbs in The Last 20 Years in Brazil

Chronic Limb Ischemia (CLI) is a severe stage of peripheral arterial disease characterized by reduced blood flow to the extremities, often leading to amputations and high morbidity and mortality rates. Treatment options include open revascularization or endovascular techniques such as angioplasty, which is less invasive but requires more frequent reinterventions. This observational and retrospective study compares hospital data for open revascularization and infrainguinal angioplasty in Brazil from 2004 to 2023, using SIH/SUS and DataSUS. The analysis included costs, mortality, length of stay, character of service, and demographic distribution of procedures. During this period, 114,417 angioplasty procedures and 47,502 open revascularizations were performed, with a total expenditure of $98.5 million. The number of deaths was 1,314 for angioplasty and 1,723 for revascularization, with mortality rates of 1.3% and 3.4%, respectively. The Northeast region stood out for having a higher ratio of angioplasty to open revascularization procedures.

Nesting behavior is associated with body weight and grip strength loss in mice suffering from experimental arthritis

Objective animal health evaluation is essential to determine welfare and discomfort in preclinical in vivo research. Body condition scores, body weight, and grimace scales are commonly used to evaluate well-being in murine rheumatoid arthritis (RA) and osteoarthritis experiments. However, nest-building, a natural behavior in mice, has not yet been evaluated in wild type (WT) or genetically modified rodents suffering from collagen antibody-induced arthritis (CAIA). To address this, we analyzed nesting behavior in WT mice, calcitonin gene-related peptide alpha-deficient (αCGRP-/-) mice, and calcitonin receptor-deficient (Calcr-/-) mice suffering from experimental RA compared to healthy control (CTRL) groups of the same genotypes. CAIA was induced in 10–12-week-old male mice, and clinical parameters (body weight, grip strength, clinical arthritis score, ankle size) as well as nesting behavior were assessed over 10 or 48 days. A slight positive association between the nest score and body weight and grip strength was found for animals suffering from CAIA. For the clinical arthritis score and ankle size, no significant associations were observed. Mixed model analyses confirmed these associations. This study demonstrates that clinical effects of RA, such as loss of body weight and grip strength, might negatively affect nesting behavior in mice. Assessing nesting behavior in mice with arthritis could be an additional, non-invasive and thus valuable health parameter in future experiments to monitor welfare and discomfort in mice. During severe disease stages, pre-formed nest-building material may be provided to animals suffering from arthritis.

Inpatient treatment of acute diverticulitis between 2010 and 2021 - A German nationwide study about long-term trends and effects of the SARS-CoV-2 pandemic.

The aims of this study were to analyse all hospitalizations for acute diverticulitis in Germany from 2010 to 2021 and to assess the effects of the first 2 years of the SARS-CoV-2 pandemic on hospitalizations for acute diverticulitis. Using data from the German Federal Statistical Office, we analysed fully anonymized healthcare data of hospitalizations and treatment regimens with acute diverticulitis as the main diagnosis between 2010 and 2021. Logistic regression analyses for in-hospital mortality were performed. A total of 608,162 hospitalizations were included. While the number of hospitalizations constantly increased until 2019 (+52.4%), a relative decrease of 10.1% was observed between 2019 and 2020, followed by stable numbers of hospitalizations in 2021 (+1.1% compared with 2020). In-hospital mortality showed a relative decrease of 33.2% until 2019 and thereafter a relative increase of 26.9% in 2020 and of 7.5% in 2021. A 21.6% and a 19.3% drop in hospitalizations was observed during the first and second waves of the SARS-CoV-2 pandemic, mostly affecting hospitalizations for uncomplicated diverticulitis, with a corresponding 11.6% and 16.8% increase in admissions for complicated diverticulitis. Multivariable logistic regression analyses showed significantly higher in-hospital mortality for hospitalizations in which surgery (OR = 2.76) and CT (OR = 1.32) were given, as well as lower mortality for women (OR = 0.88), whereas percutaneous drainage was not associated with higher in-hospital mortality compared with conservative treatment (OR = 0.71). This study points out the long-term trends in inpatient treatment for acute diverticulitis and the in-hospital mortality risk factors of patients hospitalized for acute diverticulitis in a large nationwide cohort, as well as changes in these trends and factors resulting from the SARS-CoV-2 pandemic. These changes might be attributable to delayed diagnosis and thus more severe stages of disease as a result of containment measures.

Parental History of Type 2 Diabetes Mellitus and PNPLA3 Polymorphism Increase the Risk of Severe Stages of Nonalcoholic Fatty Liver Disease.

In non-alcoholic fatty liver disease (NAFLD), the influence of parental history of type 2 diabetes (T2D) allied to single nucleotide polymorphisms (SNPs) in the offspring is not known. We aimed to investigate the impact of the parental history of T2D, PNPLA3 and TM6SF2 polymorphisms in liver steatosis and fibrosis. This was a case-control study involving the offspring of T2D patients and controls without a parental history of T2D. Participants underwent clinical and laboratory evaluation, transient elastography (TE) by Fibroscan® (Echosens, Fr) and genotyping for PNPLA3 and TM6SF2. Multivariate logistic regression evaluated the influence of parental history of T2D on liver steatosis and fibrosis, controlled for age, gender, metabolic traits and SNPs. 161 T2D offspring and 78 controls, 10-46years old, were included. The offspring of T2D had higher prevalences of obesity, T2D, arterial hypertension and sedentarism. Parental history of T2D was associated with fibrosis ≥ F2 (OR 8.89, CI 95% 1.09-72.01, p = 0.041) after adjustment for age, gender, metabolic traits and SNPs. PNPLA3 GG genotype was independently associated with steatosis ≥ S1 (OR 8.15, CI 95% 1.93-34.38, p = 0.004) and fibrosis ≥ F2 (OR 4.31, CI 95% 1.11-16.61, p = 0.034). The offspring of T2D patients present a worse metabolic profile and the parental history of T2D confers an increased likelihood of hepatic fibrosis, independent of metabolic factors. PNPLA3 homozygous GG, but not TM6SF2 genotypes, also impacts on this phenotype.

Histopathologic correlates of trabecular meshwork in microincisional trabeculectomy.

To report the histopathologic correlates of trabecular meshwork (TM) specimens procured by microincisional trabeculectomy (MIT) for different severities of glaucoma (early glaucoma: visual field mean deviation [MD] <-6 dB, moderate glaucoma: MD from - 6 to - 12 dB, and advanced glaucoma: MD <-12 dB). TM specimens from four patients undergoing MIT with or without cataract surgery were analyzed by routine histopathology for structural changes. The number of cells, the number of cells with spindle-shaped nuclei suggestive of epithelial-mesenchymal transformation (EMT), and the distance between the trabecular beams were calculated using different tools on freely available ImageJ software using the line or pint/count tool. The TM specimens procured from two early and two advanced glaucoma cases showed decreasing cellularity and decreased compact arrangement of the trabecular beams in severe disease stages. The number of cells and preserved architecture in all four specimens were evident, with > 50 cells being present per section in all four cases despite the glaucoma being of advanced disease stage in two patients. The TM specimens obtained from MIT can be utilized for downstream analysis using different molecular methods for studying the molecular events in the tissue from early to severe glaucoma.

OP142 Progression Analysis Versus Traditional Methods To Quantify Slowing Of Disease Progression In Alzheimer’s Disease

IntroductionNew statistical methodology, known as progression models for repeated measures (PMRM), can estimate the slowing of progression (percentage slowing or time delay) of Alzheimer’s disease from trial data on disease-modifying therapies. We compared the PMRM methodology with mixed models for repeated measures (MMRM) and Cox time-to-event analysis on simulated trial data with respect to their power and interpretability of estimates.MethodsTwo novel models were included: PMRM (estimating slowing of progression and allowing different rates across visits) and proportional-slowing PMRM. Clinical Dementia Rating (CDR) Sum of Boxes score and progression to dementia as assessed by CDR global score were the primary outcomes for MMRM/PMRM and the Cox model, respectively. Subject-level placebo arm trajectories were jointly simulated based on estimated CDR mean trajectories and joint temporal correlation structure of 538 amyloid-positive patients with mild cognitive impairment who met typical disease-modifying trial inclusion criteria from the Alzheimer’s Disease Neuroimaging Initiative study. Active arm trajectories were simulated to show an average 20 percent slowing of disease progression, compared with placebo, at each visit. We conducted 1,000 simulations across multiple scenarios, varying the number of patients per arm (200 to 700) and clinical trial duration (18 to 36 months).ResultsThe power of PMRM models was greater than that of MMRM, and much greater than that of the Cox model whose power never exceeded 45 percent. PMRM models accurately estimated the underlying treatment effect (median 20% slowed progression, which translated to a delay in progression of 5 and 7 months at trial durations of 24 and 36 months, respectively), unlike quantifications of the MMRM (median estimated 25% reduction in decline), and the Cox model (median estimated hazard ratio of 0.9).ConclusionsFor disease-modifying therapies, PMRM estimates may have a more intuitive clinical interpretation in terms of delayed progression than MMRM or Cox models and enable a description of the amount of time spent in less severe disease stages. Among all the methods studied, PMRM offered the best combination of interpretability and power.