Stages Of Thedisease Research Articles

Progress on early diagnosing Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions. The disease follows a continuum, starting with preclinical stages, progressing to mild cognitive and behavioral impairment, ultimately leading to dementia. Early detection of AD is crucial for better diagnosis and more effective treatment. However, the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive, and mostly are still not able to detect early disease state. Consequently, there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of AD. Various non-cognitive manifestations, including behavioral abnormalities, sleep disturbances, sensory dysfunctions, and physical changes, have been observed in the preclinical AD stage before occurrence of notable cognitive decline. Recent research advances have identified several biofluid biomarkers as early indicators of AD. This review focuses on these non-cognitive changes and newly discovered biomarkers in AD, specifically addressing the preclinical stages of the disease. Furthermore, it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.

STATISTICAL ANALYSIS OF THE PREVALENCE OF INTERNAL TEMPOROMANDIBULAR JOINT DISORDERS IN FEMALE PATIENTS BASED ON C. H. WILKES CLASSIFICATION

Introduction. Severity levels of temporomandibular joint dysfunction can be assessed by certain parameters based on images obtained using magnetic resonance imaging. In order to assess the condition of the joint and choose the optimal treatment plan depending on the detected changes on the magnetic resonance imaging images, the most common classification according to C. H. Wilkes was chosen. This study aimed to assess the severity of temporomandibular joint dysfunction symptoms in women of child-bearing and post-menopausal age according to the C. H. Wilkes classification. Participants and methods. 63 patients were selected: reproductive period n=45 and post-menopausal n=17. Magnetic resonance imaging is described in detail and the diagnosis according to the C. H. Wilkes classification is made. Statistical analysis was carried out by calculating the χ2 test in order to analyze the independence between categorical variables; Kendall's correlation coefficient was applied to assess the correlation between age and disease stages. Results. Diseases of the temporomandibular joint are more common among women of child-bearing age compared to women of postmenopausal age. This may be related to hormonal changes characteristic of the reproductive period: in the group of child-bearing age, there is a greater variety of stages of the disease, while in the group of post-menopausal age, stage IV prevails. This may indicate the influence of age factors on TMJ development. The relationship between age and diseases of the temporomandibular joint has a statistically significant correlation. The results of the χ2 test show a statistically significant relationship between age and TMJ disease stages. In addition, Kendall's correlation coefficient confirms the presence of a moderate degree of relationship between age and stages of the disease. Conclusion. The results of the analysis of the distribution of temporomandibular joint disease stages between age groups can serve as important data for optimizing clinical practice, improving treatment outcomes, and increasing patients' quality of life. For example, our study indicates that stage Ⅱ according to the classification of C. H. Wilkes is more common in women of reproductive age, and stage Ⅳ is more common in women of postmenopausal age. Clinicians should take this dada into account when developing individual treatment plans.

Precision Oncology: Circulating Microvesicles as New Biomarkers in a Very Early Stage of Colorectal Cancer

Background: The release of microvesicles (MVs) is an essential phenomenon for inter-cellular signaling in health and disease. The role of MVs in cancer is multidimensional and includes cancer cell survival, proliferation, and invasion. In this prospective study, we analyzed MV levels in colorectal cancer patients and assessed the importance of MV release in early-stage colorectal cancer and survival. Methods: This study included 98 patients and 15 controls. The characterization of MVs from human plasma was performed by flow cytometry using monoclonal antibodies. Results: The levels of total MVs and MUC-1-positive, tissue factor (TF)-positive, and endothelial cell-derived MVs (EMVs) were statistically significantly higher in the colon cancer patients than in the controls (p < 0.001). Furthermore, the subgroup of patients with very early-stage colorectal cancer also had statistically significant differences in the levels of the abovementioned MVs compared to the controls (p < 0.01). Highly differentiated tumors had lower levels of MUC-1-positive MVs (p < 0.02), EMVs (p < 0.002), and EMV/TF combinations (p < 0.001) versus those with tumors with low/intermediate differentiation. Conclusions: Our data demonstrate that the analysis of circulating MV levels in plasma could possibly become a tool for the early diagnosis of colon cancer at a very early stage of the disease.

Prognostic value of biohybrid screening results for assessing cancer risk using the example of lung cancer

Introduction. One of the leading places in the structure of socially significant diseases in the Russian Federation is occupied by malignant neoplasms, among which cancer of the trachea, bronchi and lung occupies the first place in terms of prevalence. Screening for lung cancer is not carried out at the federal level in Russia; recommended screening measures include questionnaires to identify risk factors for the development of the disease (including occupational) and the formation of dispensary observation groups. The study aims to assess the prognostic value of a new method of biohybrid screening of lung cancer by exhaled air. Materials and methods. Scientists conducted a study at the National Medical Research Center of Oncology of the Ministry of Health, Russian Federation, with the participation of 24 conditionally healthy volunteers and 5 patients diagnosed with lung cancer in the early stages of the disease. The design of the study is simultaneous (on-line) with blinding; experts estimated the risk of systematic errors at 10 points on the QUADAS scale. The authors examined exhaled air samples on a gas analyzer (biohybrid detector) of the BGS-APK 02SZZ model, in which the sensor were animals — gray domesticated rats (Rattus norvegicus) with microelectrode matrices implanted into the olfactory bulb, and which were in the internal (ventilated) space of the analyzer in a state of drug anesthesia. The conclusion about the presence or absence of a risk of lung cancer was formed by an artificial neural network of the analyzer, at the input of which bioelectric signals from each microelectrode were received, which were preprocessed using a system for recording the focal activity of the olfactory analyzer. The specialists confirmed the presence or absence of a risk of lung cancer by a reference method, according to computed tomography of the chest in accordance with the Lung Imaging Reporting and Data System (LungRADS™). Results. During the study, experts determined the effectiveness indicators of the method of biohybrid lung cancer screening by exhaled air: sensitivity (64%), specificity (87%), prognosticality of negative and positive conclusions about the presence/absence of disease risk (82% and 72%, respectively). Conclusion. The safety, efficiency and throughput of the investigated method, together with the reproducibility of the analyzer's conclusions, meet the criteria of practicability to ensure the first (population-based) stage of lung cancer screening.

Supplementing Best Care with Specialized Rehabilitation Treatment in Parkinson’s Disease: A Retrospective Study by Different Expert Centers

Background: This is a retrospective longitudinal study comparing 374 patients with Parkinson’s disease (PD) who were treated in centers offering a specialized program of enhanced rehabilitation therapy in addition to expert outpatient care to 387 patients with PD, who only received expert outpatient care at movement disorders centers in Italy. Methods: The data are from subjects recruited in the Parkinson’s Outcome Project (POP) at six Italian centers that are part of a multicenter collaboration for care quality improvement (the Fresco Network). The effects were measured with a baseline and a follow-up clinical evaluation of the Timed-Up-and-Go test (TUG), Parkinson’s Disease Questionnaire (PDQ-39), and Multidimensional Caregiver Strain Index (MCSI), the number of falls and hospitalizations for any cause. We used a generalized linear mixed model with the dependent variables being the response variable, which included the covariates demographics, evaluation, and treatment variables. Results: We found that the subjects who underwent specialized enhanced rehabilitation had a better motor outcome over time than those who were managed by expert neurologists but had participated in community programs for exercise and other allied health interventions. The greatest effects were seen in patients in the early stages of the disease with a high amount of vigorous exercise per week in the last six months. Similar effects were seen for PDQ39, MCSI, the number of falls, and hospitalization. Conclusions: Long-term benefits to motor function and the quality of life in patients with PD and burden reduction in their caregivers can be achieved through a systematic program of specialized enhanced rehabilitation interventions.

Real-world effectiveness, safety and immunogenicity of ocrelizumab in turkish multiple sclerosis patients: a single-center experience for 4-year follow-up.

The aim of this study was to evaluate postmarketing ocrelizumab safety and effectiveness in a real-world population with multiple sclerosis (MS) and matching these parameters among MS disease types. This was a retrospective, single-center study with MS patients treated with ocrelizumab. Demographic, clinical characteristics and immunological data were analyzed, including annualized relapse rate (ARR), relapse-free rate, Expanded Disability Status Scale (EDSS), complete blood count parameters, immunoglobulin (Ig) levels, liver function tests (LFT), hepatitis markers and adverse events in the 4-year follow-up. A total of 96 patients, 22 with relapsing-remitting MS (RRMS), 54 with secondary progressive MS (SPMS), and 20 with primary progressive MS (PPMS) who were treated with at least two doses of ocrelizumab between January 2018 and September 2023 were included in the study. Sixty-five (68%) were women and 31 (32%) were men. The mean age was 48.4 ± 11.1years (20-70years). Ninety-three patients were evaluated in the first year, 65 in the second year, 39 in the third year and 24 in the fourth year of treatment. 96% of patients were relapse-free rate in the first year, 91% in the second year, 85% in the third year and 75% in the fourth year. Eighty-six percent of patients were progression free in the 1st year of treatment, 71% in the 2nd year, in 64% in the 3rd year, and in 62% in the 4th year. During the follow-up of the cases, EDSS remained stable in 77% of RRMS patients, improved in 14%, and worsened in 9%; while EDSS remained stable in 65% of SPMS patients with attacks, it improved in 9% and worsened in 26%; while EDSS remained stable in 60% of PPMS patients, worsening was observed in 40%. There is a significant decrease in IgM and IgG values during the follow-up of ocrelizumab therapy (p < 0.001, p = 0.014). There is no significant difference in IgA, lymphocyte and neutrophil values (p = 0.713, p = 0.086, p = 0.999). No significant relationship was found between low serum IgM levels and the risk of developing infection (p > 0.05). Liver function tests was found to be within normal limits in 94% of the patients over a 4-year period. No hepatitis B, C or A infection, hepatitis B reactivation, tuberculosis, HIV infection, malignancy or drug related death occurred during 4-years follow-up. The most common side effect during ocrelizumab treatment is urinary tract infection (29%); others were upper respiratory tract infections (13%), numbness/tingling of the face, trunk, or extremities (8%), insomnia (6%), headache (5%), and soft tissue infections (cellulitis and dental abscess, 2%). Our results show that ocrelizumab reduces the frequency of attacks and prevent the disease progression in RRMS patients, and reducing the disease progression by primarily stabilizing EDSS scores in SPMS with attacks and PPMS. It is thought that the relatively high rates of urinary tract infection detected in this study may be related with advanced stage of the disease. The absence of hepatitis B reactivation, chronic infection or malignancy in the 4-year follow-up of our cases supports the long-term safety of ocrelizumab treatment. Ocrelizumab may be preferred as an effective and reliable treatment of different types of MS due to non-serious side effects.

Improving Accessibility to Patients with Interstitial Lung Disease (ILD): Barriers to Early Diagnosis and Timely Treatment in Latin America

Delayed initiation of effective antifibrotic therapy in patients with interstitial lung diseases (ILD) may influence the progression and outcome of the disease. This study analyzes the differences in the journey of patients with ILD in the Brazilian and Mexican health systems. An evaluative study was conducted in reference centers for interstitial lung diseases in Brazil and Mexico with a panel of four specialists. The patient’s journey in both countries begins when the patient seeks medical care after observing a chronic respiratory symptom. In both countries, due to diagnostic complexity, these patients arrive at ILD referral centers at an advanced stage of the disease. Once diagnosis is established, the treatment onset differs between Mexico and Brazil. In Brazil, access to antifibrotic drugs through the public health system has been a significant challenge, and their cost makes them unaffordable for most people. This situation forces medical specialists to provide only supportive care to patients until these drugs can be accessed. In Mexico, antifibrotics have been available in health sectors since 2018. Brazil and Mexico have several similarities regarding the initial journey of the patient due to diagnosis difficulties. Still, the outcome tends to be different due to a difference in access to treatment with antifibrotics. For this reason, advancing health policies that ensure proper treatment for patients with ILD is crucial for the sustainability and reliability of the health system.

Left ventricular function assessment in Kawasaki disease by two-dimensional global longitudinal systolic strain with automated function imaging.

Kawasaki disease is an acute febrile vasculitis of childhood mainly affecting children under 4 years of age. In the acute stage of the disease, heart function decreases and gradually returns to normal after treatment. However, subendocardial involvement may persist, which cannot be assessed by M-mode echocardiography. Strain echocardiography is a recently developed technique to assess subendocardial involvement of myocardial deformation. We aimed to study the stratified strain of left ventricular function in a Kawasaki patient at least 6 months after the acute stage of the disease with special conditions for entering the study using two-dimensional speckle-tracking imaging. Between September 2020 and October 2022, 27 healthy children and 27 children with a history of Kawasaki disease more than 6 months ago were evaluated using two-dimensional global longitudinal peak systolic strain with automated function imaging technology. The mean age of patients was 5.6 years. With M-mode echocardiography, ejection fraction of each group was in the normal range. Mean (± standard deviation) global longitudinal peak strain in four-chamber view of girls with Kawasaki disease was - 23.74 ± 2.77, and that in boys with Kawasaki disease was - 20.93 ± 2.06 (P value = 0.008). GLPS (global longitudinal peak strain) was compared as an overall average and as in a separate segment, which showed significant difference in two comparisons. In our study, a decrease in the function of some cardiac segments is reported. Global longitudinal peak strain in four-chamber view was significantly lower in boys. Comparing different segments, a difference in global left ventricular long-axis strain was found between the two groups. On the other hand, there was a major difference between the two groups in the basal inferolateral, basal anterolateral, and mid-inferolateral, which receives blood from Left Circumflex artery. Using stain echocardiography to detect continued subendocardial involvement in asymptomatic children with a history of Kawasaki disease for a better understanding of the condition, effective management and follow-up is recommended.

P25 Identification of early changes in extracellular microRNA biomarkers of scleroderma for point-of-care diagnosis

Abstract Introduction and aims Scleroderma is a rare autoimmune disease, characterized by excessive extracellular matrix deposition leading to chronic inflammation and fibrosis. As a progressive disease initially affecting the skin, it presents similarly to Raynaud phenomenon, which delays diagnosis and treatment. Clinical diagnostic tests lack sensitivity, therefore novel Methods of detection and sensitive biomarkers are required to improve diagnosis rates. MicroRNAs are short, stable, noncoding RNAs, often present in the extracellular space, and can be sampled from interstitial skin fluid (ISF) through the employment of hydrogel microneedles. We aim to use this technique to improve upon current clinical gold standards of diagnosing scleroderma, at earlier stages of the disease. Methods In this study, we performed next-generation small-RNA sequencing on ISF from healthy individuals, patients prior to a clinical diagnosis of scleroderma [termed very early detection of systemic sclerosis (VEDOSS)], and patients with scleroderma classified as low and high skin score, identifying a panel of microRNA biomarkers for scleroderma diagnosis. Swellable hydrogel microneedles were manufactured in house, applied to excised human tissue and preclinical mouse models to demonstrate the ability to access and quantify extracellular microRNAs in ISF. Results Patients who received a VEDOSS diagnosis have increased ISF abundance of miR-379-5p and miR-125a-5p and decreased miR-30e-3p compared with healthy patients. miR-379-5p, miR-363-3p and miR-221-3p are sensitive to the progression of scleroderma and could be used to track the disease with improved sensitivity to autoantibodies in blood or where clinical practices usually require a skin biopsy. Using preclinical models of skin disease, we could differentiate between conditions, with higher sensitivity than blood sampling using our microneedle technology. Conclusions By identifying extracellular mircoRNAs, we have shown the potential use of these sensitive biomarkers in a liquid biopsy that can be applied at point-of-care. Peptide nucleic acids complementary to our microRNA biomarkers, will be used to provide real-time on-the-chip readouts of these ­biomarkers.

The role and place of arthroscopy in the early diagnosis of monoarthrosis (literature review)

Background. Knee osteoarthritis is a progressive incurable disease that in severe cases leads to total joint replacement, which requires significant economic costs and medical and social adaptation, has a number of postoperative complications and adverse outcomes. Therefore, special attention has recently been paid to the prevention and treatment of the early stages of the disease. The purpose of the study was to conduct a systematic analysis of scientific literature on the prospects and possibilities of using arthroscopy in the early diagnosis of monoarthrosis. Material and methods. A literature search was conducted in the PubMed and MEDLINE databases for 2010–2024 using the following medical subject headings and keywords: “deforming osteoarthritis of the knee joint”, “osteoarthritis of the knee joint”, “unilateral deforming osteoarthritis of the knee joint”, “unilateral osteoarthritis of the knee joint”, “gonarthrosis”, “monoarthrosis”, “arthroscopy”, “diagnosis”, “treatment”. If necessary, literature sources beyond the search period were used in some cases. A general search revealed 48 references on the use of arthroscopy as a diagnostic and therapeutic method in the early stages of monoarthrosis. The primary exclusion concerned the literature in which arthroscopy was used for the diagnosis and treatment of late-stage knee osteoarthritis (n = 38). The secondary exclusion included literature sources that contained only background information (summary, figures, references) (n = 12). As a result, only relevant full-text articles in professional journals remained (n = 15). Results. The lack of correlation between clinical symptoms and radiological signs of knee osteoarthritis causes low availability of orthopaedic care: more than 30 % of newly diagnosed patients have a severe stage of the disease, and in some cases the pathology is detected only in connection with the manifestation of complications; the diagnosis of osteoarthritis due to a large percentage of painless development of the disease (40 %) is often established at terminal stages. All of this suggests the need for further research into the various factors that influence the frequency, prevalence, economic and social burden of knee osteoarthritis. Arthroscopy is potentially the gold standard for validating non-invasive assessment methods such as magnetic resonance imaging, as it provides high magnification and direct view of articular cartilage with non-destructive interactive assessment of its structure and functional properties. Arthroscopy allows for a more detailed description of the depth and extent of lesions, as well as the detection of subtle changes such as cartilage softening, fibrillations, and tangential peeling. Clinical symptoms and structural changes in the knee joint elements visualised during arthroscopy in patients with monoarthrosis are covered in a few studies, some of which were published 10 years ago. The results of modern arthroscopic studies can be an important contribution to the development of diagnostic and differential diagnostic criteria for the early stages of monoarthrosis. Conclusions. Based on information and analytical studies of modern scientific literature, it has been found that knee osteoarthritis is accompanied by persistent pain, significant limitation of the lower limb function, and reduced ability to work, which often leads to joint replacement. Diagnosis of osteoarthritis in the early stages is difficult due to the absence of pathognomonic clinical, radiological and laboratory parameters, and in case of monoarthrosis with synovitis, it is complicated by differentiation with specific arthritis of the knee joint. Arthroscopy allows performing the necessary scope of diagnostic and therapeutic measures with verification of the pathological process and determination of gonarthrosis stage.

THE IMPACT OF HEART FAILURE ON QUALITY OF LIFE: A MIXED METHOD STUDY

Abstract Introduction Heart failure (HF) is a significant global health problem, affecting over 64,000 people annually and resulting in high mortality rates (Savarese et al., 2023). However, for those receiving follow–up care, there is a 20% increase in 5–year survival (Braunwald, 2013). Globally, heart failure affects 1–3% of the population in developed countries, with 15 million patients in Europe and a 2% prevalence in Italy, accompanied by a 20% mortality rate (Heidenreich et al., 2022). Patients with heart failure often experience a reduction in quality of life (QoL), impacting their psychosocial well–being (Lupón, 2013). Indeed, those with lower QoL tend to experience more adverse events, such as rehospitalization and mortality (Ly et al., 2023). Therefore, it becomes crucial to assess QoL over time, utilizing new technologies for home monitoring. Continuous evaluation of QoL and the use of home monitoring technologies, such as telemedicine and telemonitoring, are essential and can have a positive impact on promoting QoL (Morken et al., 2022). OBJECTIVE: Investigate the perceived quality of life in geriatric patients with heart failure, describing the impact of the condition on QoL. Materials and Methods This mixed–methods study aims to explore QoL perception in a cohort of real–life outpatient geriatric patients with HF based on different stages of the disease. The study consists of two phases: a quantitative survey and a qualitative investigation. The KCCQ 23 scale was used to quantitatively assess self–reported QoL during in–person follow–up appointments and subsequently through phone follow–ups at 6 and/or 12 months. Additionally, the qualitative phase involved conducting semi–structured interviews via video calls. Results, Discussion and Conclusions The study involved 478 patients with heart failure, with women, who were underrepresented, reporting lower QoL than men. Analysis of interviews and subsequent triangulation of quantitative and qualitative data revealed that the QoL of HF patients is influenced by six identified themes: future perspectives, self–care, social interactions, emotional state, functional status, awareness of the disease, and awareness of one‘s health status. Furthermore, it was observed that deceased patients who received follow–up care reported significantly worse QoL scores compared to those who did not receive follow–up.

THE IMPACT OF NURSE–LED EDUCATION, ON QUALITY OF LIFE IN PATIENTS WITH HEART FAILURE DURING CARDIAC REHABILITATION: A REVIEW OF THE LITERATURE

Abstract Introduction The complex mosaic of cardiac rehabilitation (CR) in heart failure (HF) is composed of several "pieces": adherence to the rehabilitation program (Mazza &amp; Paneroni, 2019), therapeutic education, improvement of perceived QoL and self–care (Deek et al., 2017). To improve the patient‘s QoL, however, it is imperative to position them at the focal point of the care process. Several studies, have documented the favorable impact of CR on QoL in HF patients (Conway et al., 2015). Although variations in therapeutic and rehabilitative treatment plans vary according to each stage of the disease, adopting lifestyle changes is a recommended strategy regardless of the stage of HF from which the person is affected (ACC/AHA 2005; Yancy et al., 2005). However, despite the evidence–based benefits of post–discharge interventions combined with patient education in HF patients, the specific impact and benefits of nurse–led patient education alone, independent of the broader health care system, remain still unclear. Objective This review aims to investigate the influence of the nurse‘s educational role on the quality of life of patients with HF in the setting of cardiac rehabilitation. Materials and Methods A comprehensive literature review was conducted using databases such as PubMed, Scopus, CIHNAL Complete and EMBASE. The review followed the PICO methodology, with the formulation of a research question. MeSH terms and keywords were combined using Boolean operators and inclusion criteria. The primary outcome of interest was improved QoL. Relevant articles were subjected to preliminary analysis on the Rayyan platform. They were first evaluated by title and abstract, then selected for full–text reading, and finally subjected to "quality appraisal". Results, Discussion and Conclusions Individuals with HF experience a decline in QoL and are at increased risk of poor prognosis, characterized by exacerbation episodes leading to frequent re–hospitalizations and increased mortality rates (Heo et al., 2009; Rechenberg et al., 2020; Freedland et al., 2021). Therefore, improving QoL in patients with HF is a priority from both care and organizational perspectives (Ades et al., 2013; Darkins et al., 2015). Notably, a tailored CR educational program helps to improve self–care management and, consequently, improve QoL. That highlights the importance of nurse–led CR for HF patients in improving health behaviors and adherence to therapeutic practices.

Prostate cancer biomarkers: from early diagnosis to precision treatment.

Prostate cancer (PCa) is the second most prevalent cancer in men. In 2020, approximately 1,414,259 new cases were reported that accounted for 3,75,324 deaths (Sung et al. in CA 71:209-249, 2021). PCa is often asymptomatic at early stages; hence, routine screening and monitoring based on reliable biomarkers is crucial for early detection and assessment of cancer progression. Early diagnosis of disease is key step in reducing PCa-induced mortality. Biomarkers such as PSA have played vital role in reducing recent PCa deaths. Recent research has identified many other biomarkers and also refined PSA-based tests for non-invasive diagnosis of PCa in patients. Despite progress in screening methods, an important issue that influences treatment is heterogeneity of the cancer in different individuals, necessitating personalized treatment. Currently, focus is to identify biomarkers that can accurately diagnose PCa at early stage, indicate the stage of the disease, metastatic nature and chances of survival based on individual patient profile (Fig.1). Fig.1 Graphical abstract.

Progress against lung cancer, Denmark, 2008-2022.

There has been marked progress against lung cancer in Denmark. To gain further insight into the different aspects of the improvement, we examined the stage-specific incidence rates, stage-specific survival and mortality rates. We used information from the Danish Lung Cancer Registry on date of diagnosis and clinical stage to calculate age-standardised incidence rates and patient survival by sex, period and stage. Information about age-standardised lung cancer-specific mortality rates by sex and period was extracted from The Danish Health Data Authority. Firstly, the decrease in incidence rates was due to a reduction in the rates of advanced stages. Secondly, there was a gradual increase in survival across all stages, and thirdly, the mortality rates gradually decreased over time. The improvements in survival and mortality from lung cancer were due to decreasing incidence rates of advanced cancer and improvement in survival at all stages of the disease.

Mortality from Infections Associated with Health Care in Patients with HIV in Paraguay

Introduction: Few studies have evaluated HAIs in an HIV population; however, studies have suggested that patients with HIV are at a higher risk of contracting HAI because they have high rates of hospitalization and longer hospital stays. Objective: To determine mortality due to Infections Associated with Health Care in Patients with HIV in Paraguay from January to December 2018 to 2021. Methodology: This was an observational, descriptive, and cross-sectional study. The study population consisted of people over 18 years of age who died with a diagnosis of HIV infection and IAAS of both sexes during that period. The study variables were demographic, HIV-related, Baseline Viral Load, Stage of HIV infection at the time of diagnosis, Time from HIV diagnosis to death (in months), comorbidities at the time of death, microorganism isolation, presence, and location. of IAAS. Results: 93 patients with IAAS were included in the study, of which 34.4% (32) were between 20 and 29 years of age and 19.3% (18). Regarding the type of population, 79.3% (73) were in the general population, 77.6% (59) were diagnosed with AIDS, and 68.6% (59) had a baseline CD4 count of less than 200 cells/mm3. The mortality rate in 2020 was 6.7%, during 2018 it was 6.5% and in 2021 it and 6.4%. Conclusion: People with HIV, especially those who have been diagnosed in advanced stages of the disease, are more likely to develop HAIs and are related to mortality. This is due to the presence of multiple opportunistic infections and comorbidities that favor a high number of hospitalizations and longer hospital stays.

Driving Mitochondrial Fission Improves Cognitive, but not Motor Deficits in a Mouse Model of Ataxia of Charlevoix-Saguenay.

Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by loss-of-function mutation in the SACS gene, which encodes sacsin, a putative HSP70-HSP90 co-chaperone. Previous studies with Sacs knock-out (KO) mice and patient-derived fibroblasts suggested that SACSIN mutations inhibit the function of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1). This in turn resulted in mitochondrial hyperfusion and dysfunction. We experimentally tested this hypothesis by genetically manipulating the mitochondrial fission/fusion equilibrium, creating double KO (DKO) mice that also lack positive (PP2A/Bβ2) and negative (PKA/AKAP1) regulators of Drp1. Neither promoting mitochondrial fusion (Bβ2KO) nor fission (Akap1 KO) influenced progression of motor symptoms in Sacs KO mice. However, our studies identified profound learning and memory deficits in aged Sacs KO mice. Moreover, this cognitive impairment was rescued in a gene dose-dependent manner by deletion of the Drp1 inhibitor PKA/Akap1. Our results are inconsistent with mitochondrial dysfunction as a primary pathogenic mechanism in ARSACS. Instead, they imply that promoting mitochondrial fission may be beneficial at later stages of the disease when pathology extends to brain regions subserving learning and memory.

The collaborative project "Personalized medicine for oncology" (PM4Onco) as part of the Medical Informatics Initiative (MII)

The collaborative project Personalized Medicine for Oncology (PM4Onco) was launched in 2023 as part of the National Decade against Cancer (NKD) and is executed within the Medical Informatics Initiative (MII). Its aim is to establish asustainable infrastructure for the integration and use of data from clinical and biomedical research and therefore combines the experience and preliminary work of all four consortia of the MII and the leading oncology centers in Germany. The data provided by PM4Onco will be prepared in asuitable form to support decision making in molecular tumor boards. This concept and infrastructure will be extended to 23 participating partner sites and thus improve access to targeted therapies based on clinical information and analysis of molecular genetic alterations in tumors at different stages of the disease. This will help to improve the treatment and prognosis of tumor diseases.Clinical cancer registries are involved in the project to improve data quality through standardized documentation routines. Clinical experts advise on the expansion of the core datasets for personalized medicine (PM). Information on quality of life and treatment outcomes reported by patients in questionnaires, which is rarely collected outside of clinical trials, will make asignificant contribution. Patient representatives are involved from the onset to ensure that the important perspective of patients is taken into account in the decision-making process. PM4Onco thus creates an alliance between the MII, oncological centers of excellence, clinical cancer registries, young scientists, patients, and citizens to strengthen and advance PM in cancer therapy.

Delivering the diagnosis of multiple system atrophy: a multicenter survey on Japanese neurologists’ perspectives

BackgroundMultiple system atrophy (MSA) is a progressive, incurable, life-threatening neurodegenerative disease uniquely characterized by the risk of sudden death, which makes diagnosis delivery challenging for neurologists. Empirical studies on breaking a diagnosis of MSA are scarce, with no guidelines currently established. This study aimed to investigate neurologists’ current practices and experiences in delivering the diagnosis of MSA.MethodsWe conducted a multicenter online survey and employed a mixed-methods (quantitative and qualitative) study design in which responses to open-ended questions were analyzed qualitatively using critical incident technique.ResultsAmong the 194 neurologists surveyed, 166 opened the survey (response rate = 85.6%), of whom 144 respondents across various Japanese regions completed the survey. Accordingly, 92.3% and 82.8% of the participating neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, respectively. Factors independently associated with difficulties in diagnosis delivery included explaining the importance of the family decision making process in life-prolonging treatment, perceived difficulties in delivering information regarding the risk of sudden death, and perceived difficulties in differential diagnosis of MSA.ConclusionsOur findings showed that the majority of neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, which could have been associated with the difficulty of breaking the diagnosis of MSA. Difficulty in conveying bad news in MSA are caused by various factors, such as empathic burden on neurologists caused by the progressive and incurable nature of MSA, the need to explain complex and important details, including the importance of the family decision-making process in life-prolonging treatment, difficulty of MSA diagnosis, and communication barriers posed by mental status and cognitive impairment in patients or their family members. Neurologists consider various factors in explaining the risk of sudden death (e.g., patient’s personality, mental state, and degree of acceptance and understanding) and adjust their manner of communication, such as limiting their communication on such matters or avoiding the use of the term “sudden death” in the early stages of the disease. Although neurologists endeavor to meet the basic standards of good practice, there is room for the multiple aspects for improvement.

Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer’s disease

Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer’s disease (AD), particularly in the early stages of the disease. The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases. We herein demonstrated that human dental pulp stem cells (hDPSCs) mediated oxidative stress improvement and neuroreparative effects in in vitro AD models, playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons. Importantly, these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs, with the treated mice showing significant improvement in cognitive function and neuropathological features. Mechanistically, antioxidant and neuroprotective effects, as well as cognitive enhancements elicited by hDPSCs, were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway. In conclusion, our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models, which may be a tremendous potential therapeutic candidate for Alzheimer’s disease.

Challenges in Distinguishing Rectal Leiomyosarcoma from Ovarian Malignancy: A Diagnostic Conundrum

Introduction: Rectal leiomyosarcoma is a rare malignant mesenchymal tumor accounting for &lt;0.1% of all malignant colorectal neoplasms and carries a grave prognosis. Case Presentation: A 50-year-old postmenopausal, P3L3 woman presented with complaints of abdominal pain for two months, dark-colored loose stools, 10-15 episodes per day for 2-3 months, and gradual weight loss for 4-5 months. On ultrasonography and MRI of the pelvis, a large irregular lobulated ill-defined solid lesion was seen arising from the right side of the pelvis measuring 14x8x14cm. The right ovary was not observed to be separate from the mass. There was omental thickening and peritoneal deposits with ascites. The final impression suggested a right-sided malignant ovarian mass with peritoneal dissemination (ORADS-5) with a differential leiomyosarcoma. Her tumor markers (CA- 125; CA19-9, and CEA) were raised. Given the strong dilemma between ovarian malignancy and leiomyosarcoma and the advanced stage of the disease, the patient was planned for an ultrasound-guided biopsy of the lesion. The histopathological report revealed atypical spindle cell proliferation with myoid features with the presence of multiple mitotic figures. The diagnosis of rectal leiomyosarcoma was further confirmed with immunohistochemical tests, which were positive for actin and desmin and negative for CD 117 and S100. The patient was referred to oncosurgeon for further management and was planned for surgical resection followed by chemotherapy with intravenous doxorubicin. Conclusion: Rectal leiomyosarcoma is commonly misdiagnosed as ovarian malignancy because of its exophytic growth and similar clinical features at the time of the presentation. Hence, clinicians must be aware of these differentials for the successful management of cases.