Advances in nephroprotection: the therapeutic role of selenium, silver, and gold nanoparticles in renal health.

Renal toxicity is a disorder that causes considerable issues in healthcare systems world, highlighting the critical importance of creating alternative treatments. Metallic nanoparticles have recently emerged as promising therapeutic agents for nephroprotection because of their remarkable properties. Numerous disciplines, including medicine, biotechnology, and the food industry, are currently investigating and exploring metallic nanoparticles, such as selenium, silver, and gold, with promising outcomes. In this overview, we provide the most current findings on cutting-edge nephroprotection through metallic nanoparticles, especially selenium, silver, and gold nanoparticles. While outlining the benefits, we outline possible methods for developing metallic nanoparticles, characterization techniques, and nephroprotection therapies. Selenium nanoparticles (SeNPs) minimize oxidative stress, a primary cause of nephrotoxicity through cell regeneration which protects kidneys. Silver nanoparticles (AgNPs) have anti-inflammatory capabilities that help alleviate kidney damage and nephrotoxicity. Gold nanoparticles (AuNPs), which are biocompatible and immune-modifying, reduce inflammation and promote renal cell regeneration, indicating nephroprotective advantages. Renal protection via the use of metallic nanoparticles represents a promising new frontier in the fight against kidney disease and other renal disorders. Metallic nanoparticles of selenium, silver, and gold can protect the kidneys by lowering oxidative stress, reducing inflammation, and improving cell repair. Through their mechanisms, these nanoparticles effectively safeguard and repair kidney function, making them suitable for treating renal diseases. The potential applications of selenium, silver, and gold nanoparticles, as well as their complex modes of action and renal penetration, provide fresh hope for improving renal health and quality of life in patients with kidney disease. The current study highlights therapeutic ability, stability, nephroprotection, and toxicity profiles, as well as the importance of continuous research in this dynamic and evolving field.

Autologous Bone Marrow Aspiration Concentrate (BMAC) Therapy for Primary Knee Osteoarthritis-An Observational and Dose Escalation Study.

Introduction: Anti-inflammatory and anti-fibrotic properties maximize the therapeutic potential of bone marrow aspiration concentrate (BMAC) in osteoarthritis (OA) knee. There is a lack of studies to standardize the treatment procedure to make the studies done across various centers comparable to understand the lacunae better and develop further the deficiency in our understanding of BMAC for OA knee. We aimed to assess the degree of pain relief, functional outcome, and cartilage thickness with different doses of BMAC in primary OA knee. Materials and Methods: A single-centered prospective observational study was conducted with 80 patients of OA knee who were divided into 4 groups where group A (n = 20), group B (n = 20), group C (n = 20), and group D (n = 20) received intra-articular 1, 2, 5 million BMAC cells per kg body weight, and intra-articular saline, respectively. All patients were followed up with Visual Analog Scale (VAS), knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) scores both pre and post-procedurally at 1, 3, 6, and 12 months follow-up. Results: The study found no significant differences in demographics or co-morbidities across four participant groups (A, B, C, D). However, clinical outcomes varied markedly: Groups B and C showed significant improvements in pain perception (VAS scores), knee function, and quality of life (KOOS and WOMAC scores), while Group A showed marginal or non-significant changes, and Group D exhibited no significant improvements. These findings suggest that treatments in Groups B and C reached the Minimal Clinically Important Difference, significantly enhancing patient-reported outcomes. Conclusion: A dose of 2 million BMAC cells per kg body weight for knee OA serves as the better regenerative modality of choice in cartilage regeneration. With our dose-escalation study, we would be able to standardize the treatment procedure and enable global comparison of the treatment method across various regions of the world.

Exploring Potential Gender-Based Disparities in Referral for Transplant, Activation on the Waitlist and Kidney Transplantation in a Canadian Cohort.

Introduction: In the United States, women are less likely to be referred, activated on the waitlist, or undergo kidney transplant (KT) than men; contemporary Canadian data regarding access to transplant for women are lacking. Methods: Among patients initiating dialysis in Nova Scotia (NS), Canada from 2010 to 2020, we examined the association of candidate gender with overall access to KT, including the following: (i) odds of transplant referral within 1 year of dialysis initiation, (ii) odds of activation on the transplant waitlist (if referred), and (iii) time-to-transplantation (if activated) using logistic regression or Cox proportional hazards models as appropriate. Results: Among 749 patients deemed potentially eligible for transplant, women had lower transplant rates than men (adjusted hazard ratio [aHR]: 0.53, 95% confidence interval [CI]: 0.36-0.78); this was amplified among patients aged >60 years (aHR: 0.25, 95% CI: 0.09-0.69). Compared with men, women had a lower adjusted odds of transplant referral (adjusted odds ratio [aOR]: 0.57, 95% CI: 0.35-0.93) by 1 year after dialysis initiation. Among those referred, women had lower odds of waitlist activation than men (aOR: 0.58, 95% CI: 0.30-1.11); and among those activated, women had lower hazard of KT (aHR: 0.74, 95% CI: 0.51-1.09), though these differences were not statistically significant. Women in NS experience lower overall access to transplant, including less referral, activation and KT compared with men. Conclusion: Gender-based barriers to any of (or in this case each of) referral, activation, or transplantation result in inequities in access; identification of disparities at these critical decision points is an important first step toward ensuring equal access for all.

Vitamin D, PTH, and Lipid Dysregulation in Osteoarthritis: A Case-Control Study.

Introduction: Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, bone remodeling, and pain. Recent evidence suggests that Vitamin D insufficiency, alterations in parathyroid hormone (PTH) levels, and dyslipidemia may play roles in the pathophysiology of OA, affecting calcium homeostasis and bone health. We investigated the association between Vitamin D, PTH levels, lipid profile, and calcium homeostasis in OA patients. Materials and Methods: This case-control study involved 200 participants, divided into OA and control groups, at a tertiary care center from April to May 2023. Serum levels of 25-hydroxyvitamin D, PTH, total cholesterol, HDL, LDL, triglycerides, and calcium were measured. Statistical analysis was conducted to assess correlations between these biomarkers and OA status. Results: OA patients demonstrated significantly lower Vitamin D levels and higher PTH and total cholesterol levels compared to controls. Vitamin D insufficiency was prevalent, with a notable correlation between decreased Vitamin D levels, elevated PTH, and dyslipidemia. These findings suggest a potential metabolic interplay affecting OA progression and symptomatology. Conclusion: The study highlights a significant association between Vitamin D insufficiency, altered PTH levels, and lipid dysregulation in OA patients, underscoring the importance of assessing these parameters in the clinical management of OA. Further research is needed to explore the therapeutic implications of correcting Vitamin D insufficiency and lipid abnormalities in OA.

Kidney Outcomes Among Medicare Beneficiaries After Hospitalization for Heart Failure.

Importance: Kidney health has received increasing focus as part of comprehensive heart failure (HF) treatment efforts. However, the occurrence of clinically relevant kidney outcomes in contemporary populations with HF has not been well studied. Objective: To examine rates of incident dialysis and acute kidney injury (AKI) among Medicare beneficiaries after HF hospitalization. Design, Setting, and Participants: This retrospective cohort study evaluated adults aged 65 years or older who were hospitalized for HF across 372 sites in the Get With The Guidelines-Heart Failure registry in the US between January 1, 2014, and December 31, 2018. Patients younger than 65 years or requiring dialysis either during or prior to hospitalization were excluded. Data were analyzed from May 4, 2021, to March 8, 2024. Main Outcomes and Measures: The primary outcome was inpatient dialysis initiation in the year after HF hospitalization and was ascertained via linkage with Medicare claims data. Other all-cause and cause-specific hospitalizations were also evaluated. The covariate-adjusted association between discharge estimated glomerular filtration rate (eGFR) and 1-year postdischarge outcomes was examined using Cox proportional hazards regression models. Results: Overall, among 85 298 patients included in the analysis (mean [SD] age, 80 [9] years; 53% women) mean (SD) left ventricular ejection fraction was 47% (16%) and mean (SD) eGFR was 53 (29) mL/min per 1.73 m2; 54 010 (63%) had an eGFR less than 60 mL/min per 1.73 m2. By 1 year after HF hospitalization, 6% had progressed to dialysis, 7% had progressed to dialysis or end-stage kidney disease, and 7% had been readmitted for AKI. Incident dialysis increased steeply with lower discharge eGFR category: compared with patients with an eGFR of 60 mL/min per 1.73 m2 or more, individuals with an eGFR of 45 to less than 60 and of less than 30 mL/min per 1.73 m2 had higher rates of dialysis readmission (45 to <60: adjusted hazard ratio [AHR], 2.16 [95% CI, 1.86-2.51]; <30: AHR, 28.46 [95% CI, 25.25-32.08]). Lower discharge eGFR (per 10 mL/min per 1.73 m2 decrease) was independently associated with a higher rate of readmission for dialysis (AHR, 2.23; 95% CI, 2.14-2.32), dialysis or end-stage kidney disease (AHR, 2.34; 95% CI, 2.24-2.44), and AKI (AHR, 1.25; 95% CI, 1.23-1.27), with similar findings for all-cause mortality, all-cause readmission, and HF readmission. Baseline left ventricular ejection fraction did not modify the covariate-adjusted association between lower discharge eGFR and kidney outcomes. Conclusions and Relevance: In this study, older adults with HF had substantial risk of kidney complications, with an estimated 6% progressing to dialysis in the year after HF hospitalization. These findings emphasize the need for health care approaches prioritizing kidney health in this high-risk population.

Ventrolateral medullary compression by vascular contact in primary hemifacial spasm: a radiological analysis.

BACKGROUND: The neurovascular conflict (NVC) causing hemifacial spasm (HFS) can also cause compression of ventrolateral medulla (VLM) which contains the central sympathetic neurons. VLM compression has been associated with hypertension. Whether the VLM compression in HFS patients is associated with hypertension is not clear. OBJECTIVE: To determine the frequency, severity of VLM compression and its association with hypertension in HFS patients. METHODS: A cross-sectional, hospital-based, case control study and recruited 120 study subjects (50 cases of primary HFS, 30 hypertensive and 40 normotensive age-, sex- matched controls). The VLM compression was assessed in magnetic resonance imaging Constructive Interference in Steady State (CISS) 3D sequences. RESULTS: Hypertension was present in 30 cases (60%). Six patients with HFS (20%) were detected to be hypertensive after the onset of HFS. VLM compression was seen in 24 cases (48%), 7 hypertensive controls (23.3%) and 5 normotensive controls (10%) (p = 0.03). Twenty-four patients with hypertension had VLM compression and remaining 6 patients with hypertension did not have VLM compression (80% vs 20%; p = 0.02). Normotensive patients did not have VLM compression. Vertebral artery was the most common artery causing VLM compression (22 patients; 7 hypertensive and 5 normotensive controls). CONCLUSION: VLM compression is more common in HFS patients as compared to hypertensive and normotensive controls. It is more common in hypertensive HFS patients in comparison with normotensive HFS patients. Microvascular decompression is an option in hypertensive HFS patients with VLM compression if the hypertension is medically refractory.

Cause-Specific Health Care Costs Following Hospitalization for Heart Failure and Cost Offset With SGLT2i Therapy.

BACKGROUND: Little is known regarding differences in cause-specific costs between heart failure (HF) with ejection fraction (EF) ≤40% vs >40%, and potential cost implications of sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy. OBJECTIVES: This study sought to compare cause-specific health care costs following hospitalization for HF with EF ≤40% vs >40% and estimate the cost offset with implementation of SGLT2i therapy. METHODS: This study examined Medicare beneficiaries hospitalized for HF in the Get With The Guidelines-Heart Failure registry from 2016 to 2020. Mean per-patient total (excluding drug costs) and cause-specific costs from discharge through 1-year follow-up were calculated and compared between EF ≤40% vs >40%. Next, risk reductions on total all-cause and HF hospitalizations were estimated in a trial-level meta-analysis of 5 pivotal trials of SGLT2is in HF. Finally, these relative treatment effects were applied to Medicare beneficiaries eligible for SGLT2i therapy to estimate the projected cost offset with implementation of SGLT2i, excluding drug costs. RESULTS: Among 146,003 patients, 50,598 (34.7%) had EF ≤40% and 95,405 (65.3%) had EF >40%. Mean total cost through 1 year was $40,557. Total costs were similar between EF groups overall but were higher for EF ≤40% among patients surviving the 1-year follow-up period. Patients with EF >40% had higher costs caused by non-HF and noncardiovascular hospitalizations, and skilled nursing facilities (all P < 0.001). Trial-level meta-analysis of the 5 SGLT2i clinical trials estimated 11% (rate ratio: 0.89; 95% CI: 0.84-0.93; P < 0.001) and 29% (rate ratio: 0.71; 95% CI: 0.66-0.76; P < 0.001) relative reductions in rates of total all-cause and HF hospitalizations, respectively, regardless of EF. Reductions in all-cause and HF hospitalizations were projected to reduce annual costs of readmission by $2,451 to $2,668 per patient with EF ≤40% and $1,439 to $2,410 per patient with EF >40%. CONCLUSIONS: In this large cohort of older U.S. adults hospitalized for HF, cause-specific costs of care differed among patients with EF ≤40% vs >40%. SGLT2i significantly reduced the rate of HF and all-cause hospitalizations irrespective of EF in clinical trials, and implementation of SGLT2i therapy in clinical practice is projected to reduce costs by $1,439 to $2,668 per patient over the 1 year post-discharge, excluding drug costs.

The Utility of Spectroscopic MRI in Stereotactic Biopsy and Radiotherapy Guidance in Newly Diagnosed Glioblastoma.

Current diagnostic and therapeutic approaches for gliomas have limitations hindering survival outcomes. We propose spectroscopic magnetic resonance imaging as an adjunct to standard MRI to bridge these gaps. Spectroscopic MRI is a volumetric MRI technique capable of identifying tumor infiltration based on its elevated choline (Cho) and decreased N-acetylaspartate (NAA). We present the clinical translatability of spectroscopic imaging with a Cho/NAA ≥ 5x threshold for delineating a biopsy target in a patient diagnosed with non-enhancing glioma. Then, we describe the relationship between the undertreated tumor detected with metabolite imaging and overall survival (OS) from a pilot study of newly diagnosed GBM patients treated with belinostat and chemoradiation. Each cohort (control and belinostat) were split into subgroups using the median difference between pre-radiotherapy Cho/NAA ≥ 2x and the treated T1-weighted contrast-enhanced (T1w-CE) volume. We used the Kaplan-Meier estimator to calculate median OS for each subgroup. The median OS was 14.4 months when the difference between Cho/NAA ≥ 2x and T1w-CE volumes was higher than the median compared with 34.3 months when this difference was lower than the median. The T1w-CE volumes were similar in both subgroups. We find that patients who had lower volumes of undertreated tumors detected via spectroscopy had better survival outcomes.

Inactivation of highly transmissible livestock and avian viruses including influenza A and Newcastle disease virus for molecular diagnostics.

There is a critical need for an inactivation method that completely inactivates pathogens at the time of sample collection while maintaining the nucleic acid quality required for diagnostic PCR testing. This inactivation method is required to alleviate concerns about transmission potential, minimize shipping complications and cost, and enable testing in lower containment laboratories, thereby enhancing disease diagnostics through improved turn-around time. This study evaluated a panel of 10 surrogate viruses that represent highly pathogenic animal diseases. These results showed that a commercial PrimeStore® molecular transport media (PSMTM) completely inactivated all viruses tested by >99.99%, as determined by infectivity and serial passage assays. However, the detection of viral nucleic acid by qRT-PCR was comparable in PSMTM and control-treated conditions. These results were consistent when viruses were evaluated in the presence of biological material such as sera and cloacal swabs to mimic diagnostic sample conditions for non-avian and avian viruses, respectively. The results of this study may be utilized by diagnostic testing laboratories for highly pathogenic agents affecting animal and human populations. These results may be used to revise guidance for select agent diagnostic testing and the shipment of infectious substances.

Predicting the thermal distribution in a convective wavy fin using a novel training physics-informed neural network method.

Fins are widely used in many industrial applications, including heat exchangers. They benefit from a relatively economical design cost, are lightweight, and are quite miniature. Thus, this study investigates the influence of a wavy fin structure subjected to convective effects with internal heat generation. The thermal distribution, considered a steady condition in one dimension, is described by a unique implementation of a physics-informed neural network (PINN) as part of machine-learning intelligent strategies for analyzing heat transfer in a convective wavy fin. This novel research explores the use of PINNs to examine the effect of the nonlinearity of temperature equation and boundary conditions by altering the hyperparameters of the architecture. The non-linear ordinary differential equation (ODE) involved with heat transfer is reduced into a dimensionless form utilizing the non-dimensional variables to simplify the problem. Furthermore, Runge-Kutta Fehlberg's fourth-fifth order (RKF-45) approach is implemented to evaluate the simplified equations numerically. To predict the wavy fin's heat transfer properties, an advanced neural network model is created without using a traditional data-driven approach, the ability to solve ODEs explicitly by incorporating a mean squared error-based loss function. The obtained results divulge that an increase in the thermal conductivity variable upsurges the thermal distribution. In contrast, a decrease in temperature profile is caused due to the augmentation in the convective-conductive variable values.

Enhancing automotive cooling systems: composite fins and nanoparticles analysis in radiators.

Composites are driving positive developments in the automobile sector. In this study investigated the use of composite fins in radiators using computational fluid dynamics (CFD) to analyze the fluid-flow phenomenon of nanoparticles and hydrogen gas. Our world is rapidly transforming, and new technologies are leading to positive revolutions in today's society. In this study successfully analyzed the entire thermal simulation processes of the radiator, as well as the composite fin arrangements with stress efficiency rates. The study examined the velocity path, pressure variations, and temperature distribution in the radiator setup. As found that nanoparticles and composite fins provide superior thermal heat rates and results. The combination of an aluminum radiator and composite fins in future models will support the control of cooling systems in automotive applications. The final investigation statement showed a 12% improvement with nanoparticles, where the velocity was 1.61 m/s and the radiator system's pressure volume was 2.44 MPa. In the fin condition, the stress rate was 3.60 N/mm2.

Ayurvedic clinical decision-making methods to predict, prevent and manage childhood allergic disorders.

Allergy is a conundrum lacking satisfactory answers despite its global prevalence. Traditional systems of medicine may contain sustainable and effective solutions for the same. For mainstreaming them, an evaluation based on the system's own methods is inevitable rather than symptom-based correlations. Atopy is a novel entity in Ayurveda, but the methods of tripartite delineation (disease pattern, disease targets and influencing factors) of novel diseases and multifactorial approach to diagnosis and management in Ayurveda can bring about comprehensiveness in collection and categorization of data regarding the entity. This in turn can make the prediction, prevention and management of the same more precise, effective and sustainable. The article provides a template for the application of Ayurvedic biological framework in the diagnosis and management of novel diseases, with special reference to childhood allergic disorders.

Coxiella burnetii seroprevalence in domestic goat does in the United States: Prevalence, distribution, and associated risk factors.

Infection with the bacterium Coxiella burnetii can cause coxiellosis in animals and Q fever in humans. Coxiellosis a consistently underreported infectious disease. The infection can result in reproductive consequences for humans and animals. Ruminants are a reservoir for infection and humans are generally infected via aerosolized secretions, making it a public health concern. Studies of ruminant seroprevalence are generally limited in size and scope. This study determined seroprevalence in a large-scale U.S. population of female goats using serum samples from 7736 does from 24 states. This study identified C. burnetii seroprevalence in the United States domestic goat population. Overall, 14.5 % (SE = 2.3) of does were seropositive and 21.0 % (SE = 2.4) of operations had at least 1 seropositive doe. Further, operation demographics and herd management practices associated with seropositivity were as follows: the suspected or confirmed presence of caprine arthritis encephalitis (CAE), caseous lymphadenitis (CL), Johne's disease, or sore mouth in the herd in the previous 3 years, not cleaning or disinfecting the kidding areas or removing aborting does from other does, allowing visitors to access the kidding areas, and a lower percentage of adult goat inventory that were adult bucks or wethers. Furthermore, goat breed was associated with seropositivity. These data show C. burnetii seroprevalence in the United States and identify operation and animal characteristics and management practices associated with C. burnetii seropositivity. Together, this information can be used to help limit animal transmission, inform public health measures, and help educate and protect individuals working with goats.

Outcomes of Integrated Home Dialysis Care: Results From the Canadian Organ Replacement Register.

RATIONALE & OBJECTIVE: The integrated home dialysis model proposes the initiation of kidney replacement therapy (KRT) with peritoneal dialysis (PD) and a timely transition to home hemodialysis (HHD) after PD ends. We compared the outcomes of patients transitioning from PD to HHD with those initiating KRT with HHD. STUDY DESIGN: Observational analysis of the Canadian Organ Replacement Register (CORR). SETTINGS & PARTICIPANTS: All patients who initiated PD or HHD within the first 90 days of KRT between 2005 and 2018. EXPOSURE: Patients transitioning from PD to HHD (PD+HHD group) versus patients initiating KRT with HHD (HHD group). OUTCOME: (1) A composite of all-cause mortality and modality transfer (to in-center hemodialysis or PD for 90 days) and (2) all hospitalizations (considered as recurrent events). ANALYTICAL APPROACH: A propensity score analysis for which PD+HHD patients were matched 1:1 to (1) incident HHD patients ("incident-match" analysis) or (2) HHD patients with a KRT vintage at least equivalent to the vintage of PD+HHD patients at the transition time ("vintage-matched" analysis). Cause-specific hazards models (composite outcome) and shared frailty models (hospitalization) were used to compare groups. RESULTS: Among 63,327 individuals in the CORR, 163 PD+HHD patients (median of 1.9 years in PD) and 711 HHD patients were identified. In the incident-match analysis, compared to the HHD patients, the PD+HHD group had a similar risk of the composite outcome (HR, 0.88 [95% CI, 0.58-1.32]) and hospitalizations (HR, 1.04 [95% CI, 0.76-1.41]). In the vintage-match analysis, PD+HHD patients had a lower hazard for the composite outcome (HR, 0.61 [95% CI, 0.40-0.94]) but a similar hospitalization risk (HR, 0.85 [95% CI, 0.59-1.24]). LIMITATIONS: Risk of survivor bias in the PD+HHD cohort and residual confounding. CONCLUSIONS: Controlling for KRT vintage, the patients transitioning from PD to HHD had better clinical outcomes than the incident HHD patients. These data support the use of integrated home dialysis for patients initiating home-based KRT. PLAIN-LANGUAGE SUMMARY: The integrated home dialysis model proposes the initiation of dialysis with peritoneal dialysis (PD) and subsequent transition to home hemodialysis (HHD) once PD is no longer feasible. It allows patients to benefit from initial lifestyle advantages of PD and to continue home-based treatments after its termination. However, some patients may prefer to initiate dialysis with HHD from the outset. In this study, we compared the long-term clinical outcomes of both approaches using a large Canadian dialysis register. We found that both options led to a similar risk of hospitalization. In contrast, the PD-to-HHD model led to improved survival when controlling for the duration of kidney failure.

Polyacrylonitrile and polyethersulfone based co-axial electrospun nanofibers for fluoride removal from contaminated stream.

Coaxial electrospun polyacrylonitrile (PAN) and polyethersulfone (PES) based nanofibers were prepared and was used for filtration of fluoride from drinking water for the first time. Well defined fiber geometry was obtained at 1 ml/h of core polymer, i.e., PES flow rate, 1.4 ml/h of shell polymer, i.e., PAN flow rate, voltage of 22 kV, while the distance between the needle tip and the collector was 15-17 cm. Increase in bead like structure in fiber strands was observed with higher PAN concentration, while it decreased for lower PES concentration, thereby giving an optimum composition (6 wt% PAN and 10 wt% PES) for uniform fiber morphology. This nanofiber, abbreviated as N2 acted as an ultrafiltration membrane having permeability in the lower range, i.e., 0.5 × 10-11 m/s Pa and its fluoride removal efficacy was 46%. Fibers were also hydrophilic with considerable porous nature. Uptake of fluoride by this N2 nanofibers were evident from binding energy of 685.2 eV during XPS analysis. It is probable that nitrile and sulfone groups present in the core and shell of the nanofibers played an active in fluoride uptake, which was estimated as 110 mg/g at 298 K. Isoelectric point was in alkaline range which promoted negative fluoride ion uptake on positive nanofiber surface. Lead played higher masking effect in the uptake of fluoride in comparison to arsenic as coexisting ion. Dynamic cross flow filtration was also studied with this nanofiber in both synthetic and real life feed solution.

A Fully Automated Post-Surgical Brain Tumor Segmentation Model for Radiation Treatment Planning and Longitudinal Tracking.

Glioblastoma (GBM) has a poor survival rate even with aggressive surgery, concomitant radiation therapy (RT), and adjuvant chemotherapy. Standard-of-care RT involves irradiating a lower dose to the hyperintense lesion in T2-weighted fluid-attenuated inversion recovery MRI (T2w/FLAIR) and a higher dose to the enhancing tumor on contrast-enhanced, T1-weighted MRI (CE-T1w). While there have been several attempts to segment pre-surgical brain tumors, there have been minimal efforts to segment post-surgical tumors, which are complicated by a resection cavity and postoperative blood products, and tools are needed to assist physicians in generating treatment contours and assessing treated patients on follow up. This report is one of the first to train and test multiple deep learning models for the purpose of post-surgical brain tumor segmentation for RT planning and longitudinal tracking. Post-surgical FLAIR and CE-T1w MRIs, as well as their corresponding RT targets (GTV1 and GTV2, respectively) from 225 GBM patients treated with standard RT were trained on multiple deep learning models including: Unet, ResUnet, Swin-Unet, 3D Unet, and Swin-UNETR. These models were tested on an independent dataset of 30 GBM patients with the Dice metric used to evaluate segmentation accuracy. Finally, the best-performing segmentation model was integrated into our longitudinal tracking web application to assign automated structured reporting scores using change in percent cutoffs of lesion volume. The 3D Unet was our best-performing model with mean Dice scores of 0.72 for GTV1 and 0.73 for GTV2 with a standard deviation of 0.17 for both in the test dataset. We have successfully developed a lightweight post-surgical segmentation model for RT planning and longitudinal tracking.

Reducing Dietary Acid With Fruit and Vegetables Versus Oral Alkali in People With Chronic Kidney Disease (ReDACKD): A Clinical Research Protocol.

Background: Individuals with chronic kidney disease (CKD) can develop metabolic acidosis which, in turn, is associated with faster progression of CKD and an increased need for dialysis. Oral sodium bicarbonate (the current standard of care therapy for metabolic acidosis) is poorly tolerated leading to low adherence. Base-producing or alkalizing Fruit and vegetables have potential as an alternative treatment for metabolic acidosis as they have been shown to reduce acid load arising from the diet. Objective: This trial will evaluate the feasibility of providing base-producing fruit and vegetables as a dietary treatment for metabolic acidosis, compared with oral sodium bicarbonate. Design: A 2-arm, open-label, dual-center, randomized controlled feasibility trial. Setting: Two Canadian sites: a nephrology clinic in Winnipeg, Manitoba, and a nephrology clinic in Halifax, Nova Scotia. Participants: Adult participants with G3-G5 CKD and metabolic acidosis. Measurements: Participants will undergo baseline measurements and attend 5 study visits over 12 months at which they will have a measurement of feasibility criteria as well as blood pressure, blood and urine biochemistry, 5-repetition chair stand test (STS5), and questionnaires to assess quality of life and symptoms. Furthermore, participants fill out Automated Self-Administered 24-hour recalls (ASA-24) in the beginning, middle, and end of trial. Methods: A total of 40 eligible participants will be randomized 1:1 to either base-producing fruit and vegetables (experimental) group or sodium bicarbonate (control) group, beginning from a daily dose of 1500 mg. Limitations: Using self-administered dietary assessments, lack of supervision over the consumption of study treatments and the possible disappointment of the control group for not receiving fruit and vegetables would be considered as limitations for this study. However, we are planning to undertake proper practices to overcome the possible limitations. These practices are discussed throughout the article in detail. Conclusions: This study will generate data on base-producing fruit and vegetables consumption as a dietary treatment for metabolic acidosis in CKD. The data will be used to design a future multi-center trial looking at slowing CKD progression in people with metabolic acidosis. Trial Registration: This study is registered on clinicaltrials.gov with the identifier NCT05113641.

Contexte: Les personnes atteintes d'insuffisance rénale chronique (IRC) courent le risque de développer une acidose métabolique, laquelle est associée à une progression plus rapide de l'IRC et à un besoin accru de dialyse. La prise de bicarbonate de sodium par voie orale (la norme actuelle de traitement de l'acidose métabolique) est mal tolérée, ce qui se traduit par une faible adhérence. Les fruit et légumes basiques ou alcalifiants ont un potentiel de traitement alternatif pour l'acidose métabolique, car il a été démontré qu'ils peuvent réduire la charge acide provenant de l'alimentation. Objectif: cet essai permettra d'évaluer la faisabilité d'un traitement alimentaire de l'acidose métabolique, en misant sur la consommation de fruit et légumes basiques ou alcalifiants, par rapport à la prise de bicarbonate de sodium par voie orale. Type d'étude: essai de faisabilité contrôlé, randomisé, ouvert, à deux bras, mené dans deux centres. Cadre: deux sites canadiens, soit une clinique de néphrologie à Winnipeg (Manitoba) et une autre à Halifax (Nouvelle-Écosse). Sujets: des patients adultes atteints d'IRC de stade G3-G5 et d'acidose métabolique. Mesures: les participants seront soumis à des mesures initiales et devront se présenter à cinq visites d'étude réparties sur 12 mois. Au cours de chacune, les patients subiront une mesure des critères de faisabilité, une mesure de la pression artérielle, un bilan sanguin et urinaire, un test de lever de chaise à cinq répétitions (STS5 ­ Five Times Sit to Stand Test) et devront répondre à des questionnaires évaluant la qualité de vie et les symptômes. Les participants devront également utiliser un outil en ligne de rappels alimentaires de 24 heures autoadministrés et automatisés (ASA24 ­ Automated Self-Administered 24-hours) au début, à mi-parcours et à la fin de l'essai. Méthodologie: 40 patients admissibles seront randomisés (1:1) dans le groupe expérimental (fruit et légumes basiques ou alcalifiants) ou dans le groupe témoin (bicarbonate de sodium) avec une dose quotidienne initiale de 1 500 mg. Limites: l'utilisation d'outils d'évaluation alimentaire autoadministrés, le manque de supervision de la consommation des traitements à l'étude et la possible déception du groupe témoin de ne pas recevoir de fruit et légumes constituent des limites pour cette étude. Nous prévoyons cependant adopter des pratiques appropriées pour surmonter ces possibles limites. Ces pratiques sont discutées plus en détail dans le manuscrit. Conclusion: cette étude produira des données sur la consommation de fruit et légumes basiques ou alcalifiants comme traitement alimentaire pour l'acidose métabolique en contexte d'IRC. Ces données seront utilisées pour concevoir un futur essai multicentrique visant à ralentir la progression de l'IRC chez les personnes atteintes d'acidose métabolique. Enregistrement de l'essai: Cette étude a reçu l'approbation du Conseil d'éthique de la recherche en santé de l'Université du Manitoba (HS24768 [B2021:025]) et est enregistrée sur ClinicalTrials.gov avec l'identifiant NCT05113641.

Incidence of resting-state functional connectivity to secondary language areas and contralateral language areas in patients with brain tumors.

PURPOSE: Secondary language areas, including the pre-supplementary motor area (pre-SMA), dorsolateral prefrontal cortex (DLPFC), and the visual word form area (VWFA) play important roles in speech, but have been under-evaluated in the realm of resting-state (rs)-fMRI. The purpose of this study is to determine the incidence that secondary language areas and contralateral language areas can be localized using seed-based correlation (SBC) rs-fMRI. METHODS: We retrospectively reviewed 40 rs-fMRIs for functional connectivity (FC) to secondary language areas in cases where FC to Broca's or Wernicke's area near tumor in the left hemisphere were successfully generated using SBC analysis. Logistical regression was used for statistical analysis. RESULTS: SBC rs-fMRI with a seed in the left Broca's or Wernicke's area ipsilateral to the tumor was performed in the 40 patients. 72.5% of cases showed FC to the left DLPFC, 67.5% to left pre-SMA, and 52.5% of cases had FC to right Broca's area. In addition to other correlations, we found older patients have a lower incidence of FC to the right Wernicke's area when seeded from both left Broca's and left Wernicke's area (p-value = .016, odds ratio = 0.94). CONCLUSION: SBC rs-fMRI can detect left hemispheric secondary language areas as well as right hemispheric primary and secondary language areas. The left DLPFC showed the highest incidence of FC, followed by the left pre-SMA when seeded from both left Broca's and Wernicke's area. Logistics regression also showed in some instances, differences in the incidence of FC to language areas was dependent on age, seed location, and gender.