Disease Patients Research Articles

A Taxonomy of Low-Power Techniques in Wearable Medical Devices for Healthcare Applications

Chronic diseases are the most prevalent and non-communicable health crisis globally. Most chronic disease patients require continuous physiological monitoring, using wearable technology for timely treatment, precise illness detection, and preventive healthcare. Nonetheless, efficient power management is required for such resource-constrained wearable devices. This work aims to analyze low-power techniques (LPTs) in wearable medical devices using a data-driven approach and identify novel approaches promising higher power savings. Through an intensive literature analysis, we identify the most relevant LPTs for minimizing power consumption in wearable devices for physiological monitoring while recognizing the barriers to adopting these techniques. As a result, a novel taxonomy based on the common characteristics of the LPTs is proposed, along with strategies for the combination of LPTs. Through our analysis, we propose possible enhancements in using LPTs and suggest mechanisms for the medical device industry to facilitate their adoption. Overall, our proposed strategies guide the use of LPTs on wearable medical devices toward continuous physiological monitoring.

Prevalence of metabolic syndrome in sickle cell disease patients: A cross‐sectional study at a tertiary hospital in Nepal

AbstractBackgroundSickle cell disease (SCD) is the most common hemoglobinopathy caused by an autosomal recessive genetic disorder leading to increased morbidity and mortality rates. SCD is prevalent in the Tharu community in the lowland (Terai) region of Nepal. Prevalence of metabolic syndrome among adults with SCD is poorly studied.MethodologyThis prospective cross‐sectional study was conducted at Seti Provincial Hospital in Dhangadhi, Nepal, among 140 adolescents and adults with SCD, aged 15–60 years. Anthropometric and laboratory data were collected using an assisted questionnaire, and the SPSS software version 23 was used for data analysis. Descriptive and inferential statistics were used to summarize the presence of metabolic syndrome and were stratified in separate analyses by age and sex. National Cholesterol Education Program‐Adult Treatment Panel III criteria were used to define metabolic syndrome.AimThis cross‐sectional study aimed to assess the prevalence of metabolic syndrome among SCD patients with SCD registered at the Seti Provincial Hospital in Dhangadhi, Nepal.ResultsThe prevalence of metabolic syndrome in the study participants was 7.8%. Our study revealed 5% of the patients overweight, and 1.4% obese. In this study, the mean triglyceride level was 118.5 mg/dL, and the mean high‐density lipoprotein (HDL) level was 36.2 mg/dL (men) and 36.7 mg/dL (women). This study found that the mean fasting blood glucose level was 88.6 gm/dL. Similarly, 3.5% of patients had increased systolic blood pressure, and 7.8% had raised diastolic blood pressure. Study shows that changes in triglyceride level (p = 0.013), waist circumference, and HDL level (p = 0.0001 and 0.0048, respectively) are significantly associated with smoking or alcohol consumption; however, change in blood pressure (p = 0.013) and fasting blood sugar level (p = 0.086) are not associated with smoking or alcohol consumption.ConclusionStudy concluded that though a lower proportion of SCD patients met the criteria for metabolic syndrome than in studies conducted in developed countries, it is crucial to consider metabolic syndrome while managing patients with SCD. Nevertheless, the authors advocate a more comprehensive study to draw significant conclusions.

Association of CD24, CD27, and co-stimulatory molecules CD80 immunological marker expression on B-cells of human peripheral blood with development of celiac disease

Abstract: BACKGROUND: B-cells express a variety of clusters of differentiation markers during development. These markers determine the basic function of the immune phenotype specific to B-cells. Changes in the expression of these markers are linked to the development of many diseases, including chronic inflammation, autoimmune diseases, and immunodeficiency. OBJECTIVE: The current study aimed to investigate a change in CD24, CD27, and co-stimulatory molecules CD80 expression on peripheral blood B-cells and the extent of their contribution to celiac disease. MATERIALS AND METHODS: A total of 60 male children, whose ages ranged between 8 and 14 years, participated in this study. Thirty-five were identified as having celiac disease, while the control group comprised 25 children with anti-tissue transglutaminase (TG) (immunoglobulin G [IgG]), anti-tissue TG (IgA), and deamidated gliadin peptide (DGP) IgG levels normal. The frequency CD24, CD27, and CD80 expression were measured by flow cytometry. RESULTS: Celiac disease patients showed a substantial decrease in the percentage of CD24, CD27, and CD80 expression on B-cells compared to control groups. CONCLUSION: These findings suggest that numerical deficiency of CD24, CD27, and CD80 expression on B-cells in the peripheral blood mononuclear cell population, that may involve the loss of auto-tolerance that plays an important role in the immune response associated with inflammation and tissue damage in celiac disease. These immunological markers may be used as diagnostic indicators for this disease.

A Kernel Attention-based Transformer Model for Survival Prediction of Heart Disease Patients.

Survival analysis is employed to scrutinize time-to-event data, with emphasis on comprehending the duration until the occurrence of a specific event. In this article, we introduce two novel survival prediction models: CosAttnSurv and CosAttnSurv DyACT. CosAttnSurv model leverages transformer-based architecture and a softmax-free kernel attention mechanism for survival prediction. Our second model, CosAttnSurv DyACT, enhances CosAttnSurv with Dynamic Adaptive Computation Time (DyACT) control, optimizing computation efficiency. The proposed models are validated using two public clinical datasets related to heart disease patients. When compared to other state-of-the-art models, our models demonstrated an enhanced discriminative and calibration performance. Furthermore, in comparison to other transformer architecture-based models, our proposed models demonstrate comparable performance while exhibiting significant reduction in both time and memory requirements. Overall, our models offer significant advancements in the field of survival analysis and emphasize the importance of computationally effective time-based predictions, with promising implications for medical decision-making and patient care.

Association of caffeine consumption with cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease: A BALTAZAR cohort study.

We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. MCI (N=147) and AD (N=116) patients of the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) cohort reported their caffeine intake at inclusion using a dedicated survey. Associations of caffeine consumption with memory impairments and CSF biomarkers (tau, p-tau181, amyloid beta 1-42 [Aβ1-42], Aβ1-40) were analyzed using logistic and analysis of covariance models. Adjusted on Apolipoprotein E (APOE ε4), age, sex, education level, and tobacco, lower caffeine consumption was associated with higher risk to be amnestic (OR: 2.49 [95% CI: 1.13 to 5.46]; p=0.023) and lower CSF Aβ1-42 (p=0.047), Aβ1-42/Aβ1-40 (p=0.040), and Aβ1-42/p-tau181 (p=0.020) in the whole cohort. Data support the beneficial effect of caffeine consumption to memory impairments and CSF amyloid markers in MCI and AD patients. We studied the impact of caffeine consumption in the BALTAZAR cohort. Low caffeine intake is associated with higher risk of being amnestic in MCI/AD patients. Caffeine intake is associated with CSF biomarkers in AD patients.

Prioritization of Vaccines for Introduction in the National Immunization Program in the Republic of Korea

This study presents a framework for determining the prioritization of vaccine introduction in the National Immunization Program (NIP) of the Republic of Korea, with a focus on case examples assessed in 2021 and 2023. We describe the predefined criteria for evaluating the prioritization of vaccines in the NIP and the established process in the Republic of Korea. These criteria included disease characteristics, vaccine characteristics, rationality and efficiency of resource allocation, and the acceptance of immunization. The process of prioritizing NIP introduction involved several sequential steps: a demand survey, evidence collection, preliminary evaluation, priority evaluation, and decision making. In 2021 and 2023, 14 and 25 committee members participated in evaluating the prioritization of vaccines in the NIP, respectively. Overall, 13 and 19 NIP vaccine candidates were included in the 2021 and 2023 evaluations, respectively. Through the Delphi survey and consensus processes, the priority order was determined: vaccination against Rotavirus infection was the top priority in 2021, while Influenza 4v (for chronic disease patients) took precedence in 2023. This study demonstrates an evidence-based decision-making process within the healthcare field. The outlined approach may provide valuable guidance for policymakers in other countries seeking to prioritize the inclusion of new vaccines in their NIP.

Comparative Safety and Effectiveness of Ustekinumab and Anti-TNF in Elderly Crohn's Disease Patients.

Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the elderly. The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients ≥60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment persistence. Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23; 95% confidence interval, 0.57-2.61; P = .594) and serious infection incidence (hazard ratio, 1.38; 95% confidence interval, 0.25-7.57; P = .709) by 6 months. We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients.

The clinical value of noninvasive left ventricular myocardial work in the diagnosis of myocardial ischemia in coronary heart disease: a comparative study with coronary flow reserve fraction.

The prompt and precise identification of hemodynamically significant coronary artery lesions remains an ongoing challenge. This study investigated the diagnostic value of non-invasive global left ventricular myocardial work indices by echocardiography in functional status of coronary artery disease (CAD) patients with myocardial ischemia using fractional flow reserve (FFR) as the gold standard. A total of 77 consecutive patients with clinically suspected CAD were prospectively enrolled. All participants sequentially underwent echocardiography, invasive coronary angiography (ICA) and FFR measurement. According to the results of ICA, patients were divided into myocardial ischemia group (FFR ≤ 0.8, n = 27) and non-myocardial ischemia group (FFR > 0.8, n = 50). Myocardial work indices including global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), global positive work (GPW), global negative work (GNW), global systolic constructive work (GSCW) and global systolic wasted work (GSWW) were obtained by using the non-invasive left ventricular pressure strain loop (PSL) technique. Compared with the non-myocardial ischemia group, GWI, GCW, GPW and GSCW were significantly decreased in the myocardial ischemia group at either the 18-segment level or the 12-segment level (P < 0.001). At the 18-segment level, GWI < 1783.6 mmHg%, GCW < 1945.4 mmHg%, GPW < 1788.7 mmHg% and GSCW < 1916.5 mmHg% were optimal cut-off value to detect myocardial ischemia with an FFR ≤ 0.8. Global left ventricular myocardial work indices by echocardiography exhibited a good diagnostic value in patients with CAD and may have a good clinical significance for the screening of suspected myocardial ischemia.

Prevalence of Juvenile-Onset and Pediatric Huntington’s Disease and Their Availability and Ability to Participate in Trials: A Dutch Population and Enroll-HD Observational Study

Background: Juvenile-onset Huntington’s disease (JHD) represents 1–5% of Huntington’s disease (HD) patients, with onset before the age of 21. Pediatric HD (PHD) relates to a proportion of JHD patients that is still under 18 years of age. So far, both populations have been excluded from interventional trials. Objective: Describe the prevalence and incidence of JHD and PHD in the Netherlands and explore their ability to participate in interventional trials. Methods: The prevalence and incidence of PHD and JHD patients in the Netherlands were analyzed. In addition, we explored proportions of JHD patients diagnosed at pediatric versus adult age, their diagnostic delay, and functional and modelled (CAP100) disease stage in JHD and adult-onset HD patients at diagnosis. Results: The prevalence of JHD and PHD relative to the total manifest HD population in January 2024 was between 0.84–1.25% and 0.09–0.14% respectively. The mean incidence of JHD patients being diagnosed was between 0.85–1.28 per 1000 patient years and of PHD 0.14 per 1.000.000 under-aged person years. 55% of JHD cases received a clinical diagnosis on adult age. At diagnosis, the majority of JHD patients was functionally compromised and adolescent-onset JHD patients were significantly less independent compared to adult-onset HD patients. Conclusions: In the Netherlands, the epidemiology of JHD and PHD is lower than previously suggested. More than half of JHD cases are not eligible for trials in the PHD population. Furthermore, higher functional dependency in JHD patients influences their ability to participate in trials. Lastly, certain UHDRS functional assessments and the CAP100 score do not seem appropriate for this particular group.

One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study.

This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD). Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120). Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment. Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.

Meeting Report: 2023 Muscular Dystrophy Association Summit on ‘Safety and Challenges in Gene Therapy of Neuromuscular Diseases’

This meeting report summarizes the presentations and discussions held at the summit on Challenges in Gene Therapy hosted by the Muscular Dystrophy Association (MDA) in 2023. Topics covered include safety issues, mitigation strategies and practical considerations pertaining to the clinical translation of gene therapies for neuromuscular disease. The listing of actionable recommendations will assist in overall efforts in the field to achieve safe and efficacious translation of gene therapies for neuromuscular disease patients.

Perceived Penalties for Sharing Patient Beliefs with Health Care Providers.

Health care interactions may require patients to share with a physician information they believe but is incorrect. While a key piece of physicians' work is educating their patients, people's concerns of being seen as uninformed or incompetent by physicians may lead them to think that sharing incorrect health beliefs comes with a penalty. We tested people's perceptions of patients who share incorrect information and how these perceptions vary by the reasonableness of the belief and its centrality to the patient's disease. We recruited 399 United States Prolific.co workers (357 retained after exclusions), 200 Prolific.co workers who reported having diabetes (139 after exclusions), and 244 primary care physicians (207 after exclusions). Participants read vignettes describing patients with type 2 diabetes sharing health beliefs that were central or peripheral to the management of diabetes. Beliefs included true and incorrect statements that were reasonable or unreasonable to believe. Participants rated how a doctor would perceive the patient, the patient's ability to manage their disease, and the patient's trust in doctors. Participants rated patients who shared more unreasonable beliefs more negatively. There was an extra penalty for incorrect statements central to the patient's diabetes management (sample 1). These results replicated for participants with type 2 diabetes (sample 2) and physician participants (sample 3). Participants believed that patients who share incorrect information with their physicians will be penalized for their honesty. Physicians need to be educated on patients' concerns so they can help patients disclose what may be most important for education. Understanding how people think they will be perceived in a health care setting can help us understand what they may be wary to share with their physicians.People think that patients who share incorrect beliefs will be viewed negatively.Helping patients share incorrect beliefs can improve care.

Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an annual incidence of two cases/100 000. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. CML is characterized by a balanced genetic translocation, t(9;22) (q34;q11.2), involving a fusion of the Abelson murine leukemia (ABL1) gene from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein. Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib, are approved by the United States Food and Drug Administration (FDA) for first-line treatment of newly diagnosed CML in the chronic phase (CML-CP). Clinical trials with second and third-generation TKIs in frontline CML-CP therapy reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of their potent efficacy and the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. All four TKIs are equivalent if the aim of therapy is to improve survival. In younger patients with high-risk disease and in whom the aim of therapy is to induce a treatment-free remission status, second-generation TKIs may be favored. For CML post-failure on frontline therapy, second-line options include second and third-generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities and financial status, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP and failure (due to resistance) of at least two TKIs and for all patients in advanced-phase disease. Older patients who have a cytogenetic relapse post-failure on all TKIs can maintain long-term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non-TKI anti-CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, and others).

A randomised study comparing performance and safety of Eyestil Plus® vs Vismed Multi® in moderate-to-severe dry eye syndrome patients.

This clinical investigation compared the performance and safety of Eyestil Plus® (SIFI) and Vismed Multi® (TRB Chemedica) for reducing keratitis lesions in moderate-to-severe dry eye disease (DED) patients. This was a randomised, double-blind, multicentre investigation. 96 adults (>18 years of age) with moderate-to-severe DED received Eyestil Plus® (N = 48) or Vismed Multi® (n = 48) 6 times daily for 3 months. The primary objective clinical performance after 1 month as global corneal and conjunctival staining scores. The secondary objectives were clinical performance after 3 months, tear film stability (tear break up time (TBUT), tear production (Schirmer test), patient-reported outcomes (PROs), investigator satisfaction, and safety. 96 participants were randomised to receive the clinical investigations' treatments, 82.3% of them were female and their mean age was 65.8 years. The non-inferiority of Eyestil Plus® for moderate-to-severe DED was demonstrated at 1 month. No statistical difference was found for any of the study's objectives: change at 1 and 3 months of the global corneal and conjunctival staining score (p-value = 0.506 and 0.661, respectively), change at 1 and 3 months (p-value = 0.538 and 0.302) for TBUT test; change at 3 months for Schirmer test (p-value = 0.540). There were no changes for PROs either. Investigator satisfaction was high for both products. 16.6% of the participants experienced adverse events. This clinical investigation showed the non-inferiority of Eyestil Plus® compared to Vismed Multi® regarding performance and safety in a moderate-to-severe DED population.

Astrocyte-derived apolipoprotein D is required for neuronal survival in Parkinson’s disease

Apolipoprotein D (ApoD), a lipocalin transporter of small hydrophobic molecules, plays an essential role in several neurodegenerative diseases. It was reported that increased immunostaining for ApoD of glial cells surrounding dopaminergic (DAergic) neurons was observed in the brains of Parkinson’s disease (PD) patients. Although preliminary findings supported the role of ApoD in neuroprotection, its derivation and effects on the degeneration of nigral DAergic neurons are largely unknown. In the present study, we observed that ApoD levels released from astrocytes were increased in PD models both in vivo and in vitro. When co-cultured with astrocytes, due to the increased release of astrocytic ApoD, the survival rate of primary cultured ventral midbrain (VM) neurons was significantly increased with 1-methyl-4-phenylpyridillium ion (MPP+) treatment. Increased levels of TAp73 and its phosphorylation at Tyr99 in astrocytes were required for the increased ApoD levels and its release. Conditional knockdown of TAp73 in the nigral astrocytes in vivo could aggravate the neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD mice. Our findings reported that astrocyte-derived ApoD was essential for DAergic neuronal survival in PD models, might provide new therapeutic targets for PD.

Comparisons between In-Check DIAL® and PF810® in evaluation and training inspiratory capacity for using dry powder inhalers

BackgroundDry powder inhalers (DPIs) rely on both internal resistance and patients’ inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity.MethodsThe accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland–Altman graphical analysis.ResultsPF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P < 0.05), except for healthy volunteers against medium to high resistance (R3-R5) where the ICC was insignificant. Bland–Altman plots indicated small disagreements between the two devices for both healthy volunteers and COPD patients.ConclusionsIn-Check DIAL® exhibited poor accuracy and larger measurement errors than PF810® when detecting PIFs against higher internal resistances. However, its good performance against lower internal resistances, along with its cost-effectiveness and convenience made it appropriate for primary care. PF810® showed good accuracy and repeatability and could detect additional parameters of inspiratory capacity beyond PIF, though required further studies to confirm its clinical benefits.

EXPRESS: Acute Respiratory Distress Syndrome: A Review of ARDS Across the Life Course.

Acute respiratory distress syndrome (ARDS) is a multifactorial, inflammatory lung disease with significant morbidity and mortality that predominantly requires supportive care in its management. Although initially described in adult patients, the diagnostic definitions for ARDS have evolved over time to accurately describe this disease process in pediatric and, more recently, neonatal patients. The management of ARDS in each age demographic has converged in the application of lung protective ventilatory strategies to mitigate the primary disease process and prevent its exacerbation by limiting ventilator induced lung injury. However, differences arise in the preferred ventilatory strategies or adjunctive pulmonary therapies used to mitigate each type of ARDS. In this review, we compare and contrast the epidemiology, common etiologies, pathophysiology, diagnostic criteria, and outcomes of ARDS across the lifespan. Additionally, we discuss in detail the different management strategies used for each subtype of ARDS and spotlight how these strategies were applied to mitigate poor outcomes during the COVID-19 pandemic. This review is geared toward both clinicians and clinician-scientists as it not only summarizes the latest information on disease pathogenesis and patient management in ARDS across the lifespan but also highlights knowledge gaps for further investigative efforts. We conclude by projecting how future studies can fill these gaps in research and what improvements may be envisioned in the management of NARDS and PARDS based on the current breadth of literature in adult ARDS treatment strategies.

Aberrant migration features in primary skin fibroblasts of Huntington's disease patients hold potential for unraveling disease progression using an image based machine learning tool

Huntington's disease (HD) is a complex neurodegenerative disorder with considerable heterogeneity in clinical manifestations. While CAG repeat length is a known predictor of disease severity, this heterogeneity suggests the involvement of additional genetic and environmental factors. Previously we revealed that HD primary fibroblasts exhibit unique features, including distinct nuclear morphology and perturbed actin cap, resembling characteristics seen in Hutchinson-Gilford Progeria Syndrome (HGPS). This study establishes a link between actin cap deficiency and cell motility in HD, which correlates with the HD patient disease severity. Here, we examined single-cell motility imaging features in HD primary fibroblasts to explore in depth the relationship between cell migration patterns and their respective HD patients' clinical severity status (premanifest, mild and severe). The single-cell analysis revealed a decline in overall cell motility in correlation with HD severity, being most prominent in severe HD subgroup and HGPS. Moreover, we identified seven distinct spatial clusters of cell migration in all groups, which their proportion varies within each group becoming a significant HD severity classifier between HD subgroups. Next, we investigated the relationship between Lamin B1 expression, serving as nuclear envelope morphology marker, and cell motility finding that changes in Lamin B1 levels are associated with specific motility patterns within HD subgroups. Based on these data we present an accurate machine learning classifier offering comprehensive exploration of cellular migration patterns and disease severity markers for future accurate drug evaluation opening new opportunities for personalized treatment approaches in this challenging disorder.

Erythropoietin Effect on Complement Activation in Chronic Kidney Disease

The complement system is an important part of innate immunity. Despite its known protective role, the complement system may contribute to increased inflammation and tissue injury in cases where its balanced activation is disrupted. The kidneys have been shown to be largely affected by complement dysregulation. The aim of the present study was to investigate the effect of erythropoietin administration, on the complement system, in chronic kidney disease patients. The study involved 20 patients with CKD who received erythropoietin and measurements of levels of complement factors C3a and C5a and complement regulatory proteins (CregPs) CD55, CD46, and CD59. An increase in serum C3a and C5a levels was observed in response to EPO therapy. The increase in C3a was statistically significant (p &lt; 0.05) and concurrent with a statistically significant decrease in CD55 in CD4+ T cells (p &lt; 0.05) and B cells (p &lt; 0.05) and CD59 levels in CD4+ and CD8+ T cells (p &lt; 0.05) at completion of EPO therapy compared with healthy controls. The above observations demonstrate that EPO induces complement activation in patients undergoing EPO therapy with a simultaneous restriction of CRegPs expression, thus possibly allowing the uncontrolled complement activation, which may contribute to tissue injury and disease progression.

Associations between gut microbiota characteristics and non-motor symptoms following pharmacological and surgical treatments in Parkinson's disease patients.

The gut microbiota has been implicated in Parkinson's disease (PD), with alterations observed in microbial composition and reduced microbial species richness, which may influence gastrointestinal symptoms in PD patients. It remains to be determined whether the severity of gastrointestinal symptoms correlates with microbiota variations in PD patients treated pharmacologically or with subthalamic nucleus deep brain stimulation (STN-DBS) therapy. This study aims to explore how these treatments affect gut microbiota and gastrointestinal symptoms in PD, identifying specific microbial differences associated with each treatment modality. A total of 42 individuals diagnosed with PD, along with 38 age-matched household control participants, contributed stool samples for microbiota characterization. Differences in the gut microbiota across various groups of PD patients and their households were identified through comprehensive sequencing of the 16S rRNA gene amplicon sequencing. Differences in microbial communities were observed between PD patients and controls, as well as between PD patients receiving pharmacological treatment and those with STN-DBS. Pharmacologically treated advanced PD patients have higher gastrointestinal dysfunctions. Gut microbiota profile linked to STN-DBS and reduced levodopa consumption, characterized by its anti-inflammatory properties, might play a role in diminishing gastrointestinal dysfunction relative to only pharmacological treatments. Advanced PD patients on medication exhibit more gastrointestinal issues, despite relatively stable microbial diversity, indicating a complex interaction between gut microbiota, PD progression, and treatment effects. An imbalanced gut-brain axis, particularly due to reduced butyrate production, may lead to constipation by affecting the enteric nervous system, which emphasizes the need to incorporate gut microbiome insights into treatment strategies.