Disease Progression Research Articles

FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

Abstract Alzheimer's disease is characterized by deposition of amyloid-β protein (Aβ), which forms extracellular neuritic plaques, and accumulation of hyperphosphorylated tau, which aggregates to form intraneuronal neurofibrillary tangles, in the brain. The NLRP3 inflammasome may play a role in the transition from Aβ deposition to tau phosphorylation and aggregation. Because NLRP3 is primarily found in brain microglia, and tau is predominantly located in neurons, it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines. Here, we found that neurons also express NLRP3 in vitro and in vivo, and that neuronal NLRP3 regulates tau phosphorylation. Using biochemical methods, we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons. In primary neurons and the neuroblastoma cell line Neuro2A, FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when Aβ is present. In the brains of aged wild-type mice and a mouse model of Alzheimer's disease, FUBP3 expression was markedly increased in cortical neurons. Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses. We also found that FUBP3 trimmed the 5' end of DNA fragments that it bound, implying that FUBP3 functions in stress-induced responses. These findings suggest that neuronal NLRP3 may be more directly involved in the Aβ-to-phospho-tau transition than microglial NLRP3, and that Aβ fundamentally alters the regulatory mechanism of NLRP3 expression in neurons. Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice, FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

Potential Stem Cell Treatment for Common Hip Conditions: Osteoarthritis, Osteonecrosis and Gluteal Tendinopathy

Hip pathology, encompassing common conditions such as Osteoarthritis (OA), Osteonecrosis (ONFH) and gluteal tendinopathy, presents significant challenges in clinical management which often necessitate innovative treatment modalities. Stem cell therapy has emerged as a promising approach for addressing these complex hip conditions by promoting tissue regeneration and modifying disease progression. This paper aims to review the current literature on stem cell therapy for hip pathology, focusing on its application in OA, ONFH and gluteal tendinopathy. A comprehensive review of relevant studies and clinical trials was conducted by examining the safety, efficacy and potential mechanisms of action of stem cell therapy in hip conditions. Studies investigating the use of Bone Marrow-Derived Mesenchymal Stem Cells (BMMSCs), Adipose-Derived Mesenchymal Stem Cells (ADMSCs) and Tendon-Derived Stem Cells (TDSCs) were included in the analysis. The reviewed studies demonstrate promising outcomes of stem cell therapy in improving pain, functionality and halting disease progression in patients with hip OA. Intra-articular injections of MSCs have shown sustained benefits and arrested the progression of osteoarthritis. Stem cell therapy has also shown effectiveness in delaying the progression of ONFH, reducing femoral head collapse and decreasing the need for total hip replacement. Furthermore, in cases of gluteal tendinopathy, stem cell therapy has exhibited significant improvements in pain and functionality in a limited number of studies on the topic and also offers sustained relief in patients unresponsive to conventional treatments. Stem cell therapy holds immense potential as a safe and effective intervention for hip pathology and offers disease-modifying effects and sustained clinical benefits in these prevalent conditions. Further research is warranted to optimize treatment protocols, clarify mechanisms of action and validate long-term efficacy in larger cohorts.

Malignant perineurioma derived from the retroperitoneum with an aggressive clinical course: a case report

BackgroundMalignant perineurioma is a rare malignant counterpart of perineurioma derived from perineural cells. Resection is the primary option for the treatment of malignant perineuriomas; however, patients often develop recurrence after resection, and effective treatment for advanced or recurrent lesions needs to be established. This report describes a 51-year-old female with a rare malignant perineurioma in the retroperitoneum, which contributing valuable insights to the literature.Case presentationThe patient presented with abdominal distension and the imaging work-up revealed a huge hemorrhagic tumor in the retroperitoneum and obstruction of inferior vena cava by the tumor. The patient underwent surgery retrieving the tumor combined with left hemiliver and retrohepatic vena cava, which confirmed the diagnosis of a malignant perineurioma based on histopathological and immunohistochemical examination. Cancer gene panel testing identified mutations in NF2. Radiotherapy was administered for peritoneal dissemination 2 months after surgery, and the patient died from disease progression 6 months after surgery.ConclusionsThis rare case highlights the challenges in managing retroperitoneal malignant perineuriomas. The aggressive characteristics and limited treatment options for advanced malignant perineuriomas underscore the need for understanding the pathogenesis and developing effective systemic therapies. The identification of an NF2 mutation provides significant insights into potential therapeutic target.

Cercospora leaf spot management with nitrogenous fertilizers in cotton is dependent on the disease amount in the plant canopies

The aim of this study was to examine the impact of both organic and inorganic nitrogen fertilizers on the intensity and epidemiological components of Cercospora leaf spot across three different canopies of cotton plants, specifically the variety DP ACALA 90, under field conditions. Fertilizers used in the study included bovine manure, Jatropha curcas seedcake, poultry manure, and urea (the latter serving as a control). These were applied at 20 days after plant emergence and then during the flowering stage until the total nitrogen (N) dose reached 50, 100, 150, or 200 kg N per hectare. The incidence and severity of the disease were assessed starting at the reproductive stage B1 (the first visible flower bud) across the lower, middle, and upper canopies of four cotton plants, with six evaluations conducted over time. To calculate the initial inoculum (Y0) and the disease progress rate (r), the Exponential, Gompertz, and Logistic models were employed based on temporal data. The study was designed as a randomized complete block with a 4x4 factorial arrangement (fertilizer type x dose), and mean comparisons were made using Tukey's test (p ≤ 0.05). It was found that disease intensity within each canopy level varied in response to the type of nitrogen source and the applied dose, with the severity of the disease (including the area under the disease progress curve) being particularly influenced. A significant interaction between the type of fertilizer and the dose regarding the intensity of Cercospora leaf spot was observed. The Exponential model most accurately depicted the disease's temporal progression. Notably, poultry manure and urea were the fertilizers that most adversely influenced the intensity and initial inoculum (Y0) of Cercospora leaf spot across the various canopies of the cotton plants. The findings suggest that the use of organic fertilizers in cotton cultivation could represent a viable sustainable management strategy.

Erdafitinib (Balversa) for urothelial carcinoma.

Erdafitinib (Balversa – Janssen), an oral kinase inhibitor, has received full approval from the FDA for treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible FGFR3 (fibroblast growth factor receptor) genetic alterations who had disease progression on or after at least one prior line of systemic therapy.

Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson’s disease progression

SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson’s disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson’s progression markers initiative cohort. We further show that SVA_67 is polymorphic for its variable number tandem repeat domain which correlates with both regulatory properties in a luciferase reporter gene assay in vitro and differential expression of multiple genes in vivo. Additionally, this variation’s utility as a biomarker is reflected in a correlation with a number of PD progression markers. These experiments highlight the plethora of transcriptomic and phenotypic changes associated with SVA_67 polymorphism which should be considered when investigating the missing heritability of neurodegenerative diseases.

Long-term survival outcomes and immune checkpoint inhibitor retreatment in patients with advanced cervical cancer treated with camrelizumab plus apatinib in the phase II CLAP study.

Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer (CLAP study; NCT03816553). We herein present the updated long-term results of the CLAP study and explore potential biomarkers for survival. The outcomes of patients who underwent immune checkpoint inhibitor (ICI) retreatment were also reported. In this phase II trial, eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4-week cycles for up to two years. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Between January 21 and August 1, 2019, a total of 45 patients were enrolled. Data were analyzed as of July 31, 2023, representing > 48 months since treatment initiation for all patients. Nine (20.0%) patients completed the 2-year study. The median duration of response (DOR) was 16.6 months, and 45.0% of patients achieved a DOR of ≥ 24 months. The 12-month progression-free survival (PFS) rate was 40.7% (95% confidence interval [CI], 25.2-55.6), with an 18-month PFS rate of 37.8% (95% CI, 22.7-52.8). The median overall survival (OS) was 20.3 months (95% CI, 9.3-36.9), and the 24-month OS rate was 47.8% (95% CI, 31.7-62.3). Age > 50 years, programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (versus [vs.] < 1), CPS ≥ 10 (vs. < 1), high tumor mutational burden, and PIK3CA mutations were associated with improved PFS (hazard ratio [HR] < 1) and longer OS (HR < 1). Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs. Among them, 2 (25.0%) achieved a partial response, while 5 (62.5%) had stable disease. Notably, four patients who received retreatment with ICIs survived for more than 45 months. No new safety signals were identified in the present study. Long-term survival follow-up data demonstrated that camrelizumab plus apatinib has robust, sustained, and durable efficacy in patients with advanced cervical cancer who progress after first-line platinum-based chemotherapy. No new safety signals were noted with long-term treatment.

A Targeted Deep Sequencing Method to Quantify Endogenous Retrovirus Gag Sequence Variants and Open Reading Frames Expressed in Nonobese Diabetic Mice.

Endogenous retroviruses (ERVs) are involved in autoimmune diseases such as type 1 diabetes (T1D). ERV gene products homologous to murine leukemia retroviruses are expressed in the pancreatic islets of NOD mice, a model of T1D. One ERV gene, Gag, with partial or complete open reading frames (ORFs), is detected in the islets, and it contains many sequence variants. An amplicon deep sequencing analysis was established by targeting a conserved region within the Gag gene to compare NOD with T1D-resistant mice or different ages of prediabetic NOD mice. We observed that the numbers of different Gag variants and ORFs are linked to T1D susceptibility. More importantly, these numbers change during the course of diabetes development and can be quantified to calculate the levels of disease progression. Sequence alignment analysis led to identification of additional markers, including nucleotide mismatching and amino acid consensus at specific positions that can distinguish the early and late stages, before diabetes onset. Therefore, the expression of sequence variants and ORFs of ERV genes, particularly Gag, can be quantified as biomarkers to estimate T1D susceptibility and disease progression.

Novel Therapeutic Approaches in Connective Tissue Disease-Associated Interstitial Lung Disease.

Connective tissue diseases (CTD) comprise a group of autoimmune diseases that can affect multiple organs in the body including the lungs. The most common form of pulmonary involvement is interstitial lung disease (ILD). CTD-associated ILD (CTD-ILD) can take one of several courses including nonprogressive, chronically progressive, or rapidly progressive. Chronically and rapidly progressive patterns are associated with increased mortality. Limited randomized controlled trial data are available for treatment of CTD-ILD, with most data coming from systemic sclerosis-related ILD. The current first-line treatment for all CTD-ILD is immunosuppression with consideration of antifibrotics, stem cell transplant, and lung transplant in progressive disease. In this article, we review data for ILD treatment options in systemic sclerosis, rheumatoid arthritis, myositis, and primary Sjögren's syndrome-related ILDs.

Predicting patients with dementia most at risk of needing psychiatric in-patient or enhanced community care using routinely collected clinical data: retrospective multi-site cohort study.

Dementia is a common and progressive condition whose prevalence is growing worldwide. It is challenging for healthcare systems to provide continuity in clinical services for all patients from diagnosis to death. To test whether individuals who are most likely to need enhanced care later in the disease course can be identified at the point of diagnosis, thus allowing the targeted intervention. We used clinical information collected routinely in de-identified electronic patient records from two UK National Health Service (NHS) trusts to identify at diagnosis which individuals were at increased risk of needing enhanced care (psychiatric in-patient or intensive (crisis) community care). We examined the records of a total of 25 326 patients with dementia. A minority (16% in the Cambridgeshire trust and 2.4% in the London trust) needed enhanced care. Patients who needed enhanced care differed from those who did not in age, cognitive test scores and Health of the Nation Outcome Scale scores. Logistic regression discriminated risk, with an area under the receiver operating characteristic curve (AUROC) of up to 0.78 after 1 year and 0.74 after 4 years. We were able to confirm the validity of the approach in two trusts that differed widely in the populations they serve. It is possible to identify, at the time of diagnosis of dementia, individuals most likely to need enhanced care later in the disease course. This permits the development of targeted clinical interventions for this high-risk group.

Muscle Quality as a Potential Diagnostic Marker of Advanced Liver Fibrosis in Patients with Non-alcoholic Fatty Liver Disease.

Muscle-liver crosstalk plays an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). The measurement of muscle echo-intensity during ultrasonography is a real-time, non-invasive method of assessing muscle quality. In this retrospective study, we investigated the significance of poor muscle quality (namely, a greater mass of non-contractile tissue, including intramuscular fat) as a risk factor for advanced liver fibrosis and considered whether it may represent a useful tool for the diagnosis of advanced liver fibrosis. We analyzed data from 307 patients with NAFLD (143 men and 164 women) who visited the University of Tsukuba Hospital between 2017 and 2022. The patients were stratified into the following tertiles of muscle quality according to their muscle echo-intensity on ultrasonography: modest (84.1 A.U.), intermediate (97.4 A.U.), and poor (113.6 A.U.). We then investigated the relationships between muscle quality and risk factors for advanced liver fibrosis and calculated appropriate cutoff values. Patients with poor muscle quality showed a significant, 7.6-fold greater risk of liver fibrosis compared to those with modest muscle quality. Receiver operating characteristic curve analysis showed that muscle quality assessment was as accurate as the Fibrosis-4 index and NAFLD fibrosis score in screening for liver fibrosis and superior to the assessment of muscle quantity and strength, respectively. Importantly, a muscle echo-intensity of ≥92.4 A.U. may represent a useful marker of advanced liver fibrosis. Muscle quality may represent a useful means of identifying advanced liver fibrosis, and its assessment may become a useful screening tool in daily practice.

Farnesoid X receptor modulator 12β-(m-methyl-benzoyl)-11,12-dihydro oleanolic acid represses liver fibrosis by inhibiting ERK/p38 signaling pathways

Liver fibrosis is a common pathological process in the progression of several chronic liver diseases to cirrhosis and hepatocellular carcinoma. Therefore, the development of medications that can repress the progress of liver fibrosis is essential. We discovered that initially, 12β-(m-methyl-benzoyl)-11,12-dihydro oleanolic acid (12d-OA), a farnesoid X receptor (FXR) modulator, possessed potential anti-fibrotic properties. Through an in-depth study, we revealed that 12d-OA not only inhibited the expression of fibrogenic markers in the LX-2 cells and HSC-T6 cells but also exhibited significant protective effects against liver injury and liver fibrosis in bile duct ligation (BDL) rats. Further exploration of its molecular mechanism indicated that 12d-OA exerted antifibrotic activity by inhibiting the extracellular signal-regulated kinase (ERK)/stress-activated protein kinase (p38) signaling pathways. Consequently, the great effects of 12d-OA in vitro and in vivo suggest that it may be a good candidate for liver fibrosis.

Envisioning the Future of Personalized Medicine: Role and Realities of Digital Twins.

Digital twins have emerged as a groundbreaking concept in personalized medicine, offering immense potential to transform health care delivery and improve patient outcomes. It is important to highlight the impact of digital twins on personalized medicine across the understanding of patient health, risk assessment, clinical trials and drug development, and patient monitoring. By mirroring individual health profiles, digital twins offer unparalleled insights into patient-specific conditions, enabling more accurate risk assessments and tailored interventions. However, their application extends beyond clinical benefits, prompting significant ethical debates over data privacy, consent, and potential biases in health care. The rapid evolution of this technology necessitates a careful balancing act between innovation and ethical responsibility. As the field of personalized medicine continues to evolve, digital twins hold tremendous promise in transforming health care delivery and revolutionizing patient care. While challenges exist, the continued development and integration of digital twins hold the potential to revolutionize personalized medicine, ushering in an era of tailored treatments and improved patient well-being. Digital twins can assist in recognizing trends and indicators that might signal the presence of diseases or forecast the likelihood of developing specific medical conditions, along with the progression of such diseases. Nevertheless, the use of human digital twins gives rise to ethical dilemmas related to informed consent, data ownership, and the potential for discrimination based on health profiles. There is a critical need for robust guidelines and regulations to navigate these challenges, ensuring that the pursuit of advanced health care solutions does not compromise patient rights and well-being. This viewpoint aims to ignite a comprehensive dialogue on the responsible integration of digital twins in medicine, advocating for a future where technology serves as a cornerstone for personalized, ethical, and effective patient care.

Revisiting resistant hypertension in kidney disease.

As compared to controlled or uncontrolled hypertension, resistant hypertension in patients with chronic kidney disease (CKD) poses a significantly increased healthcare burden due to greater target end-organ damage including cardiovascular disease and CKD progression. Patients with CKD have two to three times higher risk of developing resistant hypertension. True resistant hypertension needs to be distinguished from apparent treatment resistant hypertension (aTRH); however, it is usually not possible in epidemiological studies. Moreover, impact of contemporary guidelines changes in the target blood pressure (BP) goal to less than 130/80 mmHg remains to be determined. Up to half of patients with CKD meet aTRH criteria using 2017 ACC/AHA target BP less than 130/80 mmHg. Excess sodium retention in extracellular and tissue compartment remains the cornerstone cause of resistance to the treatment in CKD. Maximizing and optimizing the diuretic regimen in addition to dietary sodium restriction plays a critical role in these patients. Management requires a trustworthy provider-patient relationship facilitating identification and intervention for the barriers restricting the uptake of lifestyle modifications and medications. Recently, renal denervation has been approved and many other novel agents are on the horizon for treatment of true resistant hypertension associated with CKD. This review discusses the latest in the pathophysiology, definition, identification and treatment strategies of resistant hypertension in individuals with CKD. Further investigations are required to identify the prevalence, future implication and treatment outcome data for true resistant hypertension associated with CKD.

MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ± 13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon correctedAkaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

"Diagnosed with New Health": Social Security Policy Recommendations for People with Cycstic Fibrosis in Ohio Transitioning to a Longer Lifespan

Cystic fibrosis (CF) is a chronic, progressive, genetic, and life-limiting lung disease that impacts approximately 105,000 individuals globally, including 40,000 individuals in the United States. In 2019, a revolutionary new drug, elexacaftor/ivacaftor/tezacaftor (ETI), was approved to manage some of the major symptoms of CF and dramatically increase the lifespan of people with cystic fibrosis (pwCF). Many individuals with CF cannot work full time and require Medicaid, Supplemental Security Income (SSI), Social Security Disability Insurance (SSDI), and other financial assistance programs to pay for treatments and medical expenses. Yet in recent years, pwCF who are on ETI have been increasingly losing benefits. A possible explanation for this is the effectiveness of ETI in improving lung function, creating the perception that pwCF are no longer disabled by their condition. Even with this “miracle" drug, pwCF continue to experience significant complications and vulnerabilities to their physical and mental health as well as limitations on daily living and employment. The compounded vulnerabilities these individuals experience leave them without a safety net. Social Security policies for pwCF require revisions to prevent further biopsychosocial damage to this population. Two policies will be recommended: leniency in redetermination, and CF education for those who make determination decisions.

MiR-486-5p protects against rat ischemic kidney injury and prevents the transition to chronic kidney disease and vascular dysfunction.

Acute kidney injury (AKI) increases the risk for progressive chronic kidney disease (CKD). MicroRNA (miR)-486-5p protects against kidney ischemia reperfusion (IR) injury in mice, although its longterm effects on the vasculature and development of CKD are unknown. We studied whether miR-486-5p would prevent the AKI to CKD transition in rat, and affect vascular function.Methods:Adult male rats were subjected to bilateral kidney IR followed by i.v. injection of liposomal-packaged miR-486-5p (0.5 mg/kg). Kidney function and histologic injury were assessed after 24 h and 10 weeks. Kidney endothelial protein levels were measured by immunoblot and immunofluorescence, and mesenteric artery reactivity was determined by wire myography.Results:In rats with IR, miR-486-5p blocked kidney endothelial cell increases in intercellular adhesion molecule-1 (ICAM-1), reduced neutrophil infiltration and histologic injury, and normalized plasma creatinine (p<0.001). However, miR-486-5p attenuated IR-induced kidney endothelial nitric oxide synthase (eNOS) expression (p<0.05). At 10 weeks, kidneys from rats with IR alone had decreased peritubular capillary density and increased interstitial collagen deposition (p<0.0001), and mesenteric arteries showed impaired endothelium-dependent vasorelaxation (p<0.001). These changes were inhibited by miR-486-5p. Delayed miR-486-5p administration (96 h, 3 weeks after IR) had no impact on kidney fibrosis, capillary density, or endothelial function.Conclusion:In rats, administration of miR-486-5p early after kidney IR prevents injury, and protects against CKD development and systemic endothelial dysfunction. These protective effects are associated with inhibition of endothelial ICAM-1 and occur despite reduction in eNOS. miR-486-5p holds promise for the prevention of ischemic AKI and its complications.

Atrial Arrhythmias Following Pulmonary Thromboendarterectomy: A Comprehensive Review Of Current Literature.

Chronic thromboembolic pulmonary hypertension (CTEPH) presents as a progressive vascular condition arising from previous episodes of acute pulmonary embolism, contributing to the development of pulmonary hypertension (PH). Pulmonary thromboendarterectomy (PTE) is the gold-standard surgical treatment for CTEPH; however, it may be associated with postoperative sequelae, including atrial arrhythmias (AAs). This comprehensive literature review explores the potential mechanisms for PTE-induced AAs with emphasis on the role of PH-related atrial remodelling and the predisposing factors. The identified preoperative predictors for AAs include advanced age, male gender, elevated resting heart rate, previous AAs, and baseline elevated right atrial pressure. Furthermore, we explore the available data on the association between post-PTE pericardial effusions and the development of AAs. Lastly, we briefly discuss the emerging role of radiomic analysis of epicardial adipose tissue as an imaging biomarker for predicting AAs.

Statistical analysis on the incidence and predictors of death among second-line ART patients in public hospitals of North Wollo and Waghemira Zones, Ethiopia, 2021

Acquired immune deficiency virus, caused by the human immunodeficiency virus, is a significant global health concern. Sub-Saharan Africa particularly Ethiopia faces a high prevalence of human immunodeficiency virus. In low-income settings like Ethiopia, early mortality rates are elevated due to severe opportunistic infections and advanced disease at Anti-retroviral treatment initiation. Despite available treatments, delayed treatment initiation among Human Immunodeficiency Virus -infected individuals in Africa, including Ethiopia, leads to disease progression and increased mortality risk. This study aimed to identify the factors contributing to the death of HIV patients under treatment at second line regimen in public hospitals of North Wollo and Waghemira Zones. A retrospective cohort study with 474 patients was conducted in selected hospitals of North Wollo and Waghemira Zones. A parametric Weibull regression model was employed, and the adjusted hazard ratio served as the measure of association. Variables significantly affected the outcome of the study was determined at a p-value < 0.05, along with a 95% confidence interval for the variables. The patients were within the average age of 38.6(standard deviation ± 12.5) years and majority (45.57%) had no formal education. The overall death incidence rate among second-line anti-retroviral treatment patients was 1.98 per 100-person years [95% CI 1.4—2.9%]. Poor adherence to antiretroviral treatment, male gender, and being underweight significantly increased the hazard of death. Conversely, increased anti-retroviral treatment duration had a significant and negative impact, reducing the hazard of death among patients. The study reveals a high incidence of death among second line anti-retroviral treatment users. Independent predictors include poor adherence, male gender, and underweight status, all significantly increasing the risk of death. On the positive side, the hazard of death decreases with longer anti-retroviral treatment duration. A critical concern and counseling should be given for better ART adherence, to change their nutritional status and for males.

Parent and oncologist perspectives on prognostic disclosure in advanced childhood cancer: communication pearls and pitfalls.

For children with advanced cancer and their families, communication about prognosis is critical. Unfortunately, data demonstrate that prognostic communication occurs infrequently and inconsistently across advancing illness. Prior to developing an intervention to improve prognostic communication, we aimed to (1) characterize parent and oncologist perspectives on "best" approaches for prognostic communication, and (2) explore similarities and differences between parent and oncologist perspectives. Children with poor-prognosis solid tumors, their parents, and oncologists were followed prospectively for 24months or until death. Matched semi-structured interviews were conducted with parents and oncologists 0-7days after medical encounters at timepoints of disease progression or relapse. Reflexive thematic analysis was conducted to describe parent and oncologist impressions of communication quality. A total of 68 interviews were conducted following serial disease reevaluation encounters involving 13 parents and five oncologists. Nine main themes were identified as "best" approaches: (1) speaking with honesty and clarity, (2) leaving room for hope, (3) leaning into a long-standing relationship, (4) personalizing language, (5) empowering the patient and family, (6) collaborating with the multidisciplinary team, (7) providing anticipatory guidance, (8) setting the scene, and (9) creating a therapeutic space. Parents and oncologists generally agreed on themes related to helpful communication approaches, while parents more explicitly described communication pitfalls. Parents and oncologists described clear recommendations for helpful communication strategies and pitfalls to avoid during difficult prognostic disclosure. Future work should integrate patient perspectives in the design and testing of an intervention to improve prognostic communication in advanced childhood cancer.