Slow Progression Research Articles

Therapeutic approaches for pulmonary hypertension in patients with chronic kidney disease.

Pulmonary hypertension is a common comorbidity in patients with chronic kidney disease (CKD), but therapeutic options are limited. We discuss the epidemiology of pulmonary hypertension in patients with CKD and review therapies for pulmonary hypertension with a focus on emerging treatments for pulmonary arterial hypertension (PAH). The definition of pulmonary hypertension has been updated to a lower threshold of mean pulmonary artery pressures of more than 20 mmHg, potentially leading to more patients with CKD to qualify for the diagnosis of pulmonary hypertension. Endothelin receptor antagonists, a class of medications, which demonstrated efficacy in patients with PAH, have been shown to slow progression of CKD, but their efficacy in lowering pulmonary artery pressures and their effects on reducing cardiovascular mortality in this population remains unproven. Sotatercept, a novel activin signaling inhibitor, which was previously studied in dialysis patients has been shown to increase exercise capacity in patients with PAH. These studies may lead to new specific therapies for pulmonary hypertension in patients with CKD. Pulmonary hypertension is common in patients with CKD. Although our understanding of factors leading to pulmonary hypertension in this population have evolved, evidence supporting disease-specific therapy in CKD is limited arguing for larger, long-term studies.

The optimal atropine concentration for myopia control in Chinese children: a systematic review and network Meta-analysis.

To figure out whether various atropine dosages may slow the progression of myopia in Chinese kids and teenagers and to determine the optimal atropine concentration for effectively slowing the progression of myopia. A systematic search was conducted across the Cochrane Library, PubMed, Web of Science, EMBASE, CNKI, CBM, VIP, and Wanfang database, encompassing literature on slowing progression of myopia with varying atropine concentrations from database inception to January 17, 2024. Data extraction and quality assessment were performed, and a network Meta-analysis was executed using Stata version 14.0 Software. Results were visually represented through graphs. Fourteen papers comprising 2475 cases were included; five different concentrations of atropine solution were used. The network Meta-analysis, along with the surface under the cumulative ranking curve (SUCRA), showed that 1% atropine (100%)>0.05% atropine (74.9%) >0.025% atropine (51.6%)>0.02% atropine (47.9%)>0.01% atropine (25.6%)>control in refraction change and 1% atropine (98.7%)>0.05% atropine (70.4%)>0.02% atropine (61.4%)>0.025% atropine (42%)>0.01% atropine (27.4%)>control in axial length (AL) change. In Chinese children and teenagers, the five various concentrations of atropine can reduce the progression of myopia. Although the network Meta-analysis showed that 1% atropine is the best one for controlling refraction and AL change, there is a high incidence of adverse effects with the use of 1% atropine. Therefore, we suggest that 0.05% atropine is optimal for Chinese children to slow myopia progression.

OTHR-25. ANAPLASTIC TRANSFORMATION OF DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMORS: TWO PEDIATRIC CASES

Abstract BACKGROUND Diffuse Leptomeningeal Glioneuronal Tumors (DLGT) typically have a clinical course with slow progression; however, there have been cases of anaplastic transformation. We describe the clinical presentation, radiographic features, and molecular characteristics in 2 pediatric DLGT cases that underwent aggressive transformation. METHODS Patient 1: A 20 y/o male with DLGT with BRAF-KIAA1549 fusion and loss of 1p who was first diagnosed at 2.5 y/o. Over the course of 17 years, he was treated with numerous therapies due to multiple progressions, including temozolomide, carboplatin/vincristine, selumetinib, and vinblastine. At age 17, he developed significant growth of a posterior fossa mass with solid and cystic characteristics. Resection revealed new anaplastic pathologic features. Patient 2: He was diagnosed with DLGT at age 2 y/o. Imaging demonstrated intramedullary spinal nodules at T4 and T5 with abnormal thickening and enhancement over the cerebral leptomeningeal space. A biopsy revealed DLGT with a BRAF-KIAA1549 fusion, 1p loss and Ki67 5%. He received multiple therapies including carboplatin/vincristine, vinblastine, and selumetinib. RESULTS Patient 1: Molecular characterization revealed new ATRX mutation, and CDKN2A/B homozygous deletion. Over the following 2 years, he had multiple treatments, progressions, and surgeries. Final pathology revealed significant anaplasia with Ki67 90%, ATRX loss, and mutation of PPM1D and ARID1A. He rapidly declined. Patient 2: Approximately 2.5 years after diagnosis, he developed rapid progression in the 4th and lateral ventricles. Pathology confirmed recurrent DLGT, but with high-grade transformation, H3K27M (-), H3k27m3 loss, ATRX (+), Ki67 40%. He was treated with focal irradiation followed by temozolomide/CCNU. CONCLUSION In rare cases, DLGT can undergo anaplastic transformation. Once this occurs, it behaves clinically like a high-grade glioma. Understanding the molecular underpinnings and prognostic features that lead to this transformation are important for future study.

A meta-analysis of randomized controlled clinical trials for implications of acute treatment effects on glomerular filtration rate for long-term kidney protection

Pharmacologic interventions to slow chronic kidney disease progression, such as ACE-inhibitors, angiotensin receptor blockers, or sodium glucose co-transporter 2 inhibitors, often produce acute treatment effects on glomerular filtration rate (GFR) that differ from their long-term chronic treatment effects. Observational studies assessing the implications of acute effects cannot distinguish acute effects from GFR changes unrelated to the treatment. Here, we performed meta-regression analysis of multiple trials to isolate acute effects to determine their long-term implications. In 64 randomized controlled trials (RCTs), enrolling 154,045 participants, we estimated acute effects as the mean between-group difference in GFR slope from baseline to three months, effects on chronic GFR slope (starting at three months after randomization), and effects on three composite kidney endpoints defined by kidney failure (GFR 15 ml/min/1.73m2 or less, chronic dialysis, or kidney transplantation) or sustained GFR declines of 30%, 40% or 57% decline, respectively. We used Bayesian meta-regression to relate acute effects with treatment effects on chronic slope and the composite kidney endpoints. Overall, acute effects were not associated with treatment effects on chronic slope. Acute effects were associated with the treatment effects on composite kidney outcomes such that larger negative acute effects were associated with lesser beneficial effects on the composite kidney endpoints. Associations were stronger when the kidney composite endpoints were defined by smaller thresholds of GFR decline (30% or 40%). Results were similar in a subgroup of interventions with supposedly hemodynamic effects that acutely reduce GFR. For studies with GFR 60 mL/min/1.73m2 or under, negative acute effects were associated with larger beneficial effects on chronic GFR slope. Thus, our data from a large and diverse set of RCTs suggests that acute effects of interventions may influence the treatment effect on clinical kidney outcomes.

LGG-16. BRAFV600K LOW-GRADE GLIOMA EMERGENCE DURING THERAPY FOR BRAFV600E HIGH-GRADE GLIOMA

Abstract BACKGROUND BRAFV600E mutations are prevalent in pediatric brain tumors, constituting 20% of low-grade and 5% of high-grade gliomas. Other single-nucleotide substitutions in BRAF are described in adult cancers but rarely in pediatric brain tumors. Our case sheds light on a unique scenario—a patient with a BRAF-mutated high-grade spinal glioma who later developed slowly progressive intracranial low-grade glioma, subsequently undergoing rapid high-grade transformation. METHODS Case Report RESULTS Our patient initially presented as a thirteen-year-old male with a two-month history of progressive bilateral hand weakness/paresthesias. Spine MRI revealed a fusiform expansile intramedullary neoplasm from C3-T2, brain MRI was negative. Biopsy showed an anaplastic astrocytoma with BRAFV600E mutation and MYC-N amplification. Initial treatment included proton radiation and a 2-year course of Dabrafenib/Trametinib, maintaining disease stability. After four months off therapy, he developed local progression, and re-staging brain MRI showed new cerebellar/supratentorial lesions. Dabrafenib/Trametinib was re-started until progression two years later. He developed hydrocephalus and underwent ETV and brain tumor biopsy, which revealed a low-grade glioma with BRAFV600K mutation. At this point, Dabrafenib/Trametinib continued for another 1.5 years; he exhibited slow progression of the brain tumors before a cerebellar lesion developed rapid progression. He had GTR of the rapid-growing lesion, and pathology reported a Grade 4 invasive astrocytoma harboring BRAFV600E, two VUS MTOR mutations, and MGMT promoter methylation. Current treatment involves radiation therapy concurrent with temozolomide. CONCLUSIONS While combinatorial Dabrafenib/Trametinib is effective in glioma therapy, resistance and progression challenges persist. Our case presents a unique manifestation—a patient with a spinal high-grade glioma with BRAFV600E who developed a secondary low-grade glioma with BRAFV600K in the brain, which, after several years, transformed into a high-grade glioma. Future research is crucial for comprehending the intricate role of BRAF mutations in pediatric gliomas, paving the way for improved patient outcomes.

MDB-02. RECURRNET SPINAL DESMOID FIBROMATOSIS IN A CHILD WITH APC GERMLINE MUTATION-RELATED MEDULLOBLASTOMA

Abstract BACKGROUND Familial adenomatous polyposis (FAP) is an autosomal-dominant dominant Familial Cancer Syndrome FCs Caused by Germline inactivation of adenomatous polyposis coli (APC) tumor suppressor gene, results in up-regulation of the WNT signaling pathway which increases the risk of colorectal cancer CRC, colon polyposis and extracolonic tumors like gastric and duodenal carcinomas WNT-activated Medulloblastoma MBL and Desmoid fibromatosis (DF) DF are locally aggressive soft tissue tumors with high local recurrence rates after Surgical excision role of adjuvant chemotherapy or Radiotherapy is still unclear. METHODS A 6-year-old boy product of non-consanguineous marriage with positive family HX brain tumor Diagnosed with Non-Metastatic Average Risk MBL WHO grade IV classic histology, he had craniotomy and Gross tumor resection followed by craniospinal irradiation at 23.4 Gy, plus a boost to posterior fossa/tumor bed up to 54 Gy, followed by 8 maintenance chemotherapy cycles as HIT-MED protocol Cisplatin/VCR/CCNU total. 3 years post end of therapy the pateint was in complete remission from MBL when routing MRI surveillance showed a new left paravertebral muscle lesion within the irradiation field from T1 to T4 levels which progressed gradually over a short follow-up time he had surgical resection of the tumor with Pathological diagnosis of Desmoid fibromatosis. after six months he had a second recurrence of the spinal tumor that needed a second surgical resection. Result: positive Genetic testing for Germline pathogenic mutation of APC gene exons 7 to 16 confirmed the diagnosis of autosomal familial adenomatous polyposis type 1(FAP1). Up to date, he is stable on endoscopic and MRI surveillance with radiological evidence of slow progression of the paraspinal tumor CONCLUSION Medulloblastomas associated with APC germline mutation have favorable outcomes that may need de-escalating therapeutic protocol with reduced intensity craniospinal irradiation aiming to reduce the incidence of secondary tumors after adjuvant treatment for MBL

LGG-54. PEDIATRIC LOW-GRADE GLIOMAS TREATED WITH MEK INHIBITORS

Abstract BACKGROUND Low-grade gliomas (LGG) represent the most common brain tumor in children. It is well known that these tumors present mutations involving the BRAF gene, causing activation of the MAPK/ERK pathway. MEK inhibitors have now become an important treatment option over the recent years, slowing the growth of cancer cells. METHODS Retrospective analysis of 23 patients with LGG that were treated with MEK inhibitors at Nicklaus Children’s Hospital between 2015-2022. RESULTS Of the 23 patients; 6 were males and 17 were females, with a median age at diagnosis of 9.5 years of age. BRAF V600E mutation was present in 52% of patients (9/17). Other mutations found were: BRAF, BRAF KIAA1549, p.Q61K, and FGFR. Six patients had known associations with NF1. 7 of 23 patients had not received any prior treatment before MEK therapy, 8 underwent partial or total resection only prior, 4 had previous chemotherapy treatment, 3 underwent resection with chemotherapy, and 1 patient had both chemotherapy and proton radiation prior to MEK therapy. Targeted therapies included Trametinib (17/23), Dabrafenib (9/23), Selumetinib (5/23), and Binimetinib (1/23). Of the 9 patients with BRAF V600E mutation, 7/9 were given dual targeted therapies whereas only two were treated with only one inhibitor. The average length of therapy was one year. Most reported side effects were dermatologic manifestations such as dry skin or acne (9/23). Five patients showed objective improvement, 16 patients had stable residual disease, one had local recurrence, and one patient expired. Currently 12 patients are off therapy and 10 remain on treatment. Of the patients with BRAF V600E mutation, 4 had clinical and/or radiologic response, 1 patient expired due to disease progression and 1 has stable disease. CONCLUSION MEK inhibitors as a treatment of pediatric low-grade gliomas demonstrated promise as a therapeutic approach, so far proving to slow progression of disease in some cases. However, long-term side effects and toxicity remain unknown. Further large-scale prospective analysis would be helpful in future studies.

Qualitative and quantitative assessment of non-clear cell renal cell carcinoma using contrast-enhanced ultrasound

BackgroundNon-clear cell renal cell carcinoma (nccRCC) represents a rare form of renal cell carcinoma (RCC) in the clinic. It is now understood that contrast-enhanced ultrasound (CEUS) exhibits diverse manifestations and can be prone to misdiagnosis. Therefore, summarizing the distinctive features of contrast-enhanced ultrasonography is essential for differentiation from ccRCC.ObjectiveThis study aims to evaluate the diagnostic efficacy of qualitative and quantitative CEUS in diagnosing nccRCC to enhance our understanding of this condition.MethodsWe conducted a retrospective analysis of 21 patients with confirmed nccRCC following surgery and assessed the characteristic conventional ultrasound and CEUS imaging features. The paired Wilcoxon signed-rank sum test was employed to compare differences in CEUS time-intensity curve (TIC) parameters between the lesions and the normal renal cortex.ResultsRoutine ultrasound revealed the following primary characteristics in the 21 nccRCC cases: hypoechoic appearance (10/21, 47.6%), absence of liquefaction (18/21, 66.7%), regular shape (19/21, 90.5%), clear boundaries (21/21, 100%), and absence of calcification (17/21, 81%). Color Doppler flow imaging (CDFI) indicated a low blood flow signal (only 1 case of grade III). Qualitative CEUS analysis demonstrated that nccRCC predominantly exhibited slow progression (76.1%), fast washout (57%), uniformity (61.9%), low enhancement (71.5%), and ring enhancement (61.9%). Quantitative CEUS analysis revealed that parameters such as PE, WiAUC, mTTI, WiR, WiPI, WoAUC, WiWoAUC, and WOR in the lesions were significantly lower than those in the normal renal cortex (Z=-3.980, -3.563, -2.427, -3.389, -3.980, -3.493, -3.528, -2.763, P < 0.001, < 0.001, = 0.015, = 0.001, < 0.001, < 0.001, < 0.001, = 0.006). However, there were no significant differences in RT, TTP, FT, or QOF (all P > 0.05).ConclusionnccRCC exhibits distinctive CEUS characteristics, including slow progression, fast washout, low homogeneity enhancement, and ring enhancement, which can aid in distinguishing nccRCC from ccRCC.

The Role of Emerging Technologies of Students' Academic Achievement at Polytechnic Seberang Perai

Education is crucial for global progress and is always changing due to the impact of current technologies. Ongoing discussions focus on how developing technologies are affecting teaching and learning approaches. This essay examines how incorporating new technology in education impacts academic success. Although technology is deemed essential for information dissemination in education, the influence of new technology on academic success is still uncertain. This research examines the elevated failure rates at Seberang Perai Polytechnic (PSP) in Malaysia, linking them to factors including insufficient information, slow progress in studies, and inadequate time management. The study seeks to investigate the influence of new technologies on academic achievement at PSP. The study uses an ex post facto research strategy and quantitative approaches to gather data from 200 respondents at PSP. The study aims to identify the new technologies used by students in various departments and evaluate how these technologies affect academic achievement. Chi-Square analysis and Spearman correlation coefficient are used to test hypotheses. The survey shows that modern technology is widely accessible, with cellphones being the most favored among pupils. Noticeable discrepancies in technological access across departments have been discovered. Weak connections exist between technology usage frequency and academic achievement, with just one statistically meaningful association discovered in obtaining material on the internet. The research helps fill the void in literature on the use of new technologies for academic objectives within the context of PSP. The results underscore the need of teaching students about efficient technology utilization to improve academic results. The study highlights that the presence of new technologies does not automatically lead to academic progress. Academic improvement relies on how students incorporate these resources into their learning methods. Suggestions involve teaching students how to use technology effectively and understanding that academic success is not guaranteed solely by using technology.

Multicentric Longitudinal Prospective Study in a European Cohort of MYO7A Patients: Disease Course and Implications for Gene Therapy.

We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene. Fifty-three patients (mean age, 33.6 ± 16.7years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed. At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9dB; 9.0 ± 10.2dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0µm; 250.7 ± 63.3µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6µm; 2615.5 ± 2370.4µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]). Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.

Spinocerebellar ataxia 27B: a frequent and slowly progressive autosomal-dominant cerebellar ataxia-experience from an Italian cohort.

Autosomal-dominant spinocerebellar ataxia (ADCA) due to intronic GAA repeat expansion in FGF14 (SCA27B) is a recent, relatively common form of late-onset ataxia. Here, we aimed to: (1) investigate the relative frequency of SCA27B in different clinically defined disease subgroups with late-onset ataxia collected among 16 tertiary Italian centers; (2) characterize phenotype and diagnostic findings of patients with SCA27B; (3) compare the Italian cohort with other cohorts reported in recent studies. We screened 396 clinically diagnosed late-onset cerebellar ataxias of unknown cause, subdivided in sporadic cerebellar ataxia, ADCA, and multisystem atrophy cerebellar type. We identified 72 new genetically defined subjects with SCA27B. Then, we analyzed the clinical, neurophysiological, and imaging features of 64 symptomatic cases. In our cohort, the prevalence of SCA27B was 13.4% (53/396) with as high as 38.5% (22/57) in ADCA. The median age of onset of SCA27B patients was 62years. All symptomatic individuals showed evidence of impaired balance and gait; cerebellar ocular motor signs were also frequent. Episodic manifestations at onset occurred in 31% of patients. Extrapyramidal features (17%) and cognitive impairment (25%) were also reported. Brain magnetic resonance imaging showed cerebellar atrophy in most cases (78%). Pseudo-longitudinal assessments indicated slow progression of ataxia and minimal functional impairment. Patients with SCA27B in Italy present as an adult-onset, slowly progressive cerebellar ataxia with predominant axial involvement and frequent cerebellar ocular motor signs. The high consistency of clinical features in SCA27B cohorts in multiple populations paves the way toward large-scale, multicenter studies.

Exploring the Gendered Dynamics of Work and Family Life. A Secondary Descriptive Analysis in the Romanian Context

This paper focuses on work and family life in Romania, with particular emphasis on gender, seen as a social structure. The methodology employs the secondary descriptive analysis of data drawn from NIS, Eurostat, and the European Value Survey/World Value Survey datasets. The findings show a Romanian work landscape with slow progress in embracing work flexibility, with considerably lower percentages of remote work and part-time employment compared to EU averages. A notable gender disparity exists in the professional sector. Women exhibit a 18.8% lower participation in economic activities compared to men, a gap that increases with the number of children. Moreover, 36.5% of women, in contrast to 2.7% of men, are professionally inactive due to familial responsibilities. These results align with Nancy Fraser’s (2013) viewpoint on how the intersection between capitalism and patriarchy shapes women experiences. The lack of family-friendly work structures disproportionately impacts women, leaving them vulnerable professionally and financially. Family continues to be the most important institution for Romanians, with trends regarding age of marriage and child births mirroring previous years. While there's a gradual decrease in unpaid household and childcare activities, it is mostly due to technological progress (Popescu, 2009) while women still work “double shifts” (Hochschild, 2012). The paper’s findings highlight that cultural norms and societal pressure compels women to prioritize family responsibilities. Creating “brave new families” (Stacy, 1990) or fostering “confluent love” (Giddens, 1992) requires post-modern cooperation between partners, backed by multi-level actions (Walby, 1989) at individual, organizational and societal levels.

High prevalence of exon-13 variants in USH2A-related retinal dystrophies in Taiwanese population

BackgroundBiallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype–phenotype correlations of USH2A-related retinal dystrophies in Taiwan.ResultsIn our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference.ConclusionsThis is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.

Kidney disease knowledge among patients visiting the nephrology clinic in the Kingdom of Saudi Arabia.

This study aimed to explore chronic kidney disease (CKD)-related knowledge and its predictors among non-dialysis patients with CKD in the Kingdom of Saudi Arabia (KSA). It was a cross-sectional survey conducted at 2 nephrology centers in KSA. Data were gathered using a survey questionnaire that included sociodemographic information and enquiries about CKD. The questionnaire used to explore CKD knowledge consisted of 24 questions with 3 multiple-choice answers for each question: "True," "False," and "I don't know." Data were obtained from 185 patients who visited a nephrology clinic. The major study population was drawn from the western region of the Kingdom of Saudi Arabia. The participants' mean (SD) total renal disease knowledge scores was 12.56 (3.55) out of a maximum of 24 points on the renal disease knowledge assessment. This suggests that the participants, on average, exhibited a moderate level of knowledge regarding renal disease. Most respondents correctly answered questions related to blood and urine tests (90.3% and 89.7%, respectively), living with a single kidney (88.1%), kidney function in blood cleansing (83.8%), risk factors like diabetes (82.7%), and hypertension (80%). Additionally, they recognized symptoms such as water retention (85.9%) and fatigue (61.6%) and the potential of certain medications to slow chronic kidney disease progression (72.4%). However, fewer respondents correctly identified nausea/vomiting (31.4%) and loss of appetite (31.4%) as signs of kidney disease, the role of kidneys in maintaining blood pressure (58.9%) and bone health (16.2%), and obesity as a risk factor (54.1%). Furthermore, there were notable differences in knowledge scores between genders, with men scoring significantly higher than women (2.05, P = .041). In general, the understanding of CKD within the CKD patient community in the KSA was at a moderate level. However, male respondents had a greater understanding of CKD than did female respondents. The findings of this study indicate an urgent need to conduct educational activities to improve CKD knowledge among patients with CKD in the KSA.

Challenges and opportunities for designing clinical trials for antibody mediated rejection.

Significant progress has been made in kidney transplantation, with 1-year graft survival nearing 95%. However, long-term allograft survival remains suboptimal, with a 10-year overall graft survival rate of only 53.6% for deceased donor transplant recipients. Chronic active antibody-mediated rejection (ABMR) is a leading cause of death-censored graft loss, yet no therapy has demonstrated efficacy in large, randomized trials, despite substantial investment from pharmaceutical companies. Several clinical trials aimed to treat chronic ABMR in the past decade have yielded disappointing results or were prematurely terminated, attributed to factors including incomplete understanding of disease mechanisms, heterogeneous patient populations with comorbidities, slow disease progression, and limited patient numbers. This review aims to discuss opportunities for improving retrospective and prospective studies of ABMR, focusing on addressing heterogeneity, outcome measurement, and strategies to enhance patient enrollment to inform study design, data collection, and reporting.

Residential renovations: Understanding cost-disruption trade-offs

Disruption and mess associated with energy efficiency retrofits is one aspect that is rarely considered in studies investigating households’ preferences for energy renovations. Using a choice experiment, we estimate a price for residential retrofit disruption, finding it represents a substantial proportion of associated energy cost savings among some households. There is considerable variance in willingness to pay for both energy cost savings and disruption avoidance, consistent with experience of many households investing in energy retrofits but also of government retrofit schemes falling far short of policy targets. Just 1-in-4 households are actively receptive to retrofit policy supports, and disruption posing a significant barrier to undertaking energy retrofits, means both contribute to the slow progress against public policy targets to improve residential energy efficiency.

Priapism as The Initial Presentation of Prostate Cancer Recurrence: A Case Report and Review of the Literature

Introduction: Prostate cancer is one of the two most common non-cutaneous cancers in men. Its presentation might have unusual symptoms, which could have caused the wrong initial diagnosis. Case Presentation: This study presents a case of prostate cancer complaining of persistent pain and erection of the penis. He had been treated with radical prostatectomy five years before his presentation. The patient had not followed his treatment for the cancer for the last four years. The patient was admitted to the hospital, and urgent imaging of the pelvis with magnetic resonance imaging showed extensive involvement of lymph nodes and corpus cavernosa. Management started with the combination of anti-androgenic and radiotherapy, which was effective and caused significant clinical improvement in the patient’s condition and improved laboratory and radiologic markers. Discussion: Prostate cancer recurrence can present with unusual symptoms considering its slow progression and involvement of the various structures. Malignant priapism is the involvement of the cavernosal system by a solid tumor. This is an indicator of a poor prognosis, and most patients' life expectancies are shorter than one year. Clinical Key Message Priapism can have a wide range of etiologies, and it can also be an indicator of malignancy progression through the genitourinary systems. In patients with a history of prostate cancer or those with a risk of this malignancy presented by priapism, appropriate diagnostic evaluation regarding this cancer should be performed. More importantly, patients treated for prostate cancer should be followed up regularly, and it should be mentioned that this cancer can slowly recur without any symptoms until it reaches a high stage.

Non-transgenic guinea pig strains exhibit divergent age-related changes in hippocampal mitochondrial respiration.

Alzheimer's disease (AD) is the most common form of dementia. However, while 150+ animal models of AD exist, drug translation from preclinical models to humans for treatment usually fails. One factor contributing to low translation is likely the absence of neurodegenerative models that also encompass the multi-morbidities of human aging. We previously demonstrated that, in comparison to the PigmEnTed (PET) guinea pig strain which models "typical" brain aging, the Hartley strain develops hallmarks of AD like aging humans. Hartleys also exhibit age-related impairments in cartilage and skeletal muscle. Impaired mitochondrial respiration is one driver of both cellular aging and AD. In humans with cognitive decline, diminished skeletal muscle and brain respiratory control occurs in parallel. We previously reported age-related declines in skeletal muscle mitochondrial respiration in Hartleys. It is unknown if there is concomitant mitochondrial dysfunction in the brain. Therefore, we assessed hippocampal mitochondrial respiration in 5- and 12-month Hartley and PET guinea pigs using high-resolution respirometry. At 12 months, PETs had higher complex I supported mitochondrial respiration paralleling their increase in body mass compared to 5 months PETs. Hartleys were also heavier at 12 months compared to 5 months but did not have higher complex I respiration. Compared to 5 months Hartleys, 12 months Hartleys had lower complex I mitochondrial efficiency and compensatory increases in mitochondrial proteins collectively suggesting mitochondrial dysfunction with age. Therefore, Hartleys might be a relevant model to test promising therapies targeting mitochondria to slow brain aging and AD progression.

Modifiable factors associated with Huntington's disease progression in presymptomatic participants.

Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms. Our aim here was to identify factors that can be modified to slow disease progression even before the first symptoms appear. We included 2636 presymptomatic individuals (comparison with family controls) drawn from the prospective observational cohort Enroll-HD, with more than 35 CAG repeats and at least two assessments of disease progression measured with the composite Huntington's disease rating Scale (cUHDRS). The association between sociodemographic factors, health behaviors, health history, and cUHDRS trajectory was assessed with a mixed-effects random forest using partial dependence plots and Shapley additive explanation method. Participants were followed by an average of 3.4 (SD = 1.97) years. We confirmed the negative impact of age and a high number of CAG repeats. We found that a high level of education, a body mass index (BMI) <23 kg/m2 before the age of 40 and >23 kg/m2 thereafter, alcohol consumption of <15 units per week, current coffee consumption and no smoking were linked to slow disease progression, as did no previous exposure to antidepressants or anxiolytic, no psychiatric history or comorbidities, and being female. Other comorbidities or marital status showed no major association with HD evolution. Reducing modifiable risk factors for HD is one way to support the presymptomatic population. A high level of education, low-to-moderate alcohol consumption, no smoking, and BMI control are likely to slow disease progression in this population.

Hybrid reverse multi-stage flash and multi-effect evaporator systems powered by low grade energy for water desalination

Integration of a reversal multistage flash (RVMSF) and multi-effect evaporators (MEE) desalination technologies driven by waste heat source is studied. The warm RVMSF reject brine is used as a sensible heat source for the MEE process. Three different configurations are compared and proved to outperform the standalone MSFRV system. Based on the best hybrid structure, 69 %, 67 %, and 287 % enhancement in the recovery ratio, the specific energy consumption (SEC), and the gain output ratio (GOR), respectively over the standard RVMSF process were observed. However, this was achieved at the expense of a 46 % increase in the specific heat transfer area. The recovery ratio, specific area, SEC, and GOR were found to improve with primary feed temperature, and temperature drop of the sensible heat powering the MEE. However, for a fixed number of effects, the full leverage of the supplied energy is limited causing variable or slow progress of the key performance indicators. Increasing the number of MEE effects had a positive effect on the performance causing proportional growth of the recovery ratio and GOR. A maximum value of 20.2 % for the recovery ratio and 5.7 for the GOR was observed when ten effects were used in the MEE system.