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BMC Nephrology May 2024Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD.... (Comparative Study)
Comparative Study
BACKGROUND
Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies.
METHODS
Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker.
RESULTS
Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics.
CONCLUSIONS
C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.
Topics: Humans; Female; Citrulline; Male; Protein Carbamylation; Biomarkers; Middle Aged; Renal Insufficiency, Chronic; Aged; Prospective Studies; Risk Assessment; Kidney Failure, Chronic; Prognosis; Proportional Hazards Models; Serum Albumin
PubMed: 38816682
DOI: 10.1186/s12882-024-03619-6 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024In patients with chronic heart failure (CHF), the use of angiotensin-converting enzyme inhibitors, including ramipril, is recommended to reduce the risk of heart failure...
In patients with chronic heart failure (CHF), the use of angiotensin-converting enzyme inhibitors, including ramipril, is recommended to reduce the risk of heart failure worsening, hospitalisation, and death. Our aim was to investigate the influence of body composition on the pharmacokinetics of ramipril and its active metabolite ramiprilat and to evaluate the changes in pharmacokinetics after prolonged therapy. Twenty-three patients with CHF who were on regular therapy with ramipril participated at the first study visit ( median age 77 years, 65 % male, and 70 % New York Heart Association Class II); 19 patients attended the second study visit and the median time between the two visits was 8 months. Pharmacokinetics were assessed using a nonlinear mixed-effects parent-metabolite model comprising two compartments for ramipril and one compartment for ramiprilat. The influence of body size and composition was best described by an allometric relationship with fat-free mass. In addition, ramipril clearance was related to patient age and daily ramipril dose, while clearance of ramiprilat was influenced by glome rular filtration rate and daily ramipril dose. There were no clinically relevant changes in the pharmacokinetics of ramipril and ramiprilat between the study visits. Due to the relatively stable pharmacokinetics of ramipril, regular outpatient visits at 6-month intervals seem appropriate to evaluate ramipril therapy.
Topics: Humans; Ramipril; Heart Failure; Male; Angiotensin-Converting Enzyme Inhibitors; Aged; Female; Longitudinal Studies; Chronic Disease; Aged, 80 and over; Middle Aged; Body Composition
PubMed: 38815200
DOI: 10.2478/acph-2024-0018 -
PloS One 2024This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment. (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVES
This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment.
METHODS
A computerized search through PubMed/MEDLINE, SCOPUS, and the Cochrane Library was conducted to find relevant papers. We used the "netmeta" and "meta" packages for network meta-analysis (NMA) in RStudio 1.2.5019 (2009-2019 RStudio, Inc.) to conduct all of our statistical tests.
RESULTS
Seven articles (n = 2,006 patients) were included. The fixed-effect size showed that TC 1% bis in die (BID) showed potential effectiveness in reducing the inflammatory and non-inflammatory lesion count compared to placebo (Standardized mean difference, SMD = -0.27, 95% CI: -0.36 to -0.17) and (SMD = -0.31, 95% CI: -0.41 to -0.22), respectively. The random-effect size showed that TC 1% BID was significantly associated with a 12-week treatment success compared to placebo (Odds ratio, OR = 2.44, 95% CI: 1.12 to 5.30). Spironolactone 200 mg was associated with a significant reduction in total lesion count (SMD = -4.46, 95% CI: -5.60 to -3.32).
CONCLUSION
TC appears to reduce both inflammatory and non-inflammatory lesion count and may lead to treatment success. Spironolactone at 200 mg showed potential effectiveness in terms of total lesion count reduction. These results suggest that both TC and Spironolactone could be beneficial in treating patients with acne vulgaris.
Topics: Acne Vulgaris; Humans; Spironolactone; Network Meta-Analysis; Treatment Outcome; Administration, Topical; Cortodoxone; Propionates
PubMed: 38814916
DOI: 10.1371/journal.pone.0298155 -
PloS One 2024The prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian...
BACKGROUND
The prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian randomization (MR) study to comprehensively screen the blood metabolomes for potential causal mediators of five frequently encountered gastrointestinal tumors (Liver Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer and Pancreatic Cancer).
METHODS
We selected a comprehensive set of 137 distinct blood metabolites derived from three large-scale genome-wide association studies (GWASs) involving a total of 147827 participants of European ancestry. The gastrointestinal tumors-related data were obtained from a GWAS conducted within the Finnish study. Through meticulous MR analyses, we thoroughly assessed the associations between blood metabolites and gastrointestinal tumors. Additionally, a phenome-wide MR (Phe-MR) analysis was employed to investigate the potential on-target side effects of metabolite interventions.
RESULTS
We have identified 1 blood metabolites, namely isovalerylcarnitine (ORlog10: 1.01; 95%CI, 1.01-1.02; P = 1.81×10-7), as the potential causal mediators for liver cancer. However, no potential pathogenic mediators were detected for the other four tumors.
CONCLUSIONS
The current systematic MR analysis elucidated the potential role of isovalerylcarnitine as a causal mediator in the development of liver cancer. Leveraging the power of Phe-MR study facilitated the identification of potential adverse effects associated with drug targets for liver cancer prevention. Considering the weighing of pros and cons, isovalerylcarnitine emerges as a promising candidate for targeted drug interventions in the realm of liver cancer prevention.
Topics: Humans; Gastrointestinal Neoplasms; Metabolome; Genome-Wide Association Study; Mendelian Randomization Analysis; Male; Female; Finland; Carnitine; Middle Aged; Risk Factors; Liver Neoplasms
PubMed: 38814898
DOI: 10.1371/journal.pone.0304574 -
European Annals of Allergy and Clinical... May 2024Epistaxis is frequently observed in allergic rhinitis (AR) patients. However, few studies focus on the outcome of epistaxis with treatment of AR patients. This study...
Epistaxis is frequently observed in allergic rhinitis (AR) patients. However, few studies focus on the outcome of epistaxis with treatment of AR patients. This study aimed to retrospectively analyze the efficacy and safety of AR patients with epistaxis treated with sublingual immunotherapy (SLIT). A total of 74 patients aged 4-60 years with house dust mite (HDM)-induced AR accompanied by epistaxis and who completed 1 year of SLIT treatment with standard Dermatophagoides farinae (D. farinae) drops were enrolled in this study. The symptom scores, total medication scores (TMS), combined symptom and medication score (CSMS), visual analog scales (VAS), and bleeding score (BS) were assessed, as well as the nasal endoscopic examinations were performed to observe nasal signs. The levels of symptom scores, TMS, CSMS, VAS, and BS at 0.5 year and 1 year of SLIT treatment were significantly lower than those at the baseline (all p less than 0.01). Also, statistical differences were seen in CSMS (p less than 0.05) and VAS (p less than 0.01) between 0.5 year and 1 year. As expected, BS was positively correlated with CSMS (r = 0.617, 95% CI 0.517-0.699) and VAS (r = 0.777, 95% CI 0.719-0.822) at all three time points. SLIT with D. farinae drops was effective and safe for AR patients with epistaxis, resulting in improving the symptoms of rhinitis while relieving the symptoms of epistaxis.
PubMed: 38813925
DOI: 10.23822/EurAnnACI.1764-1489.342 -
Turkish Journal of Medical Sciences 2023Acne vulgaris (AV) is a common inflammatory skin condition associated with psychological and social distress. Its pathogenesis involves factors such as sebaceous...
BACKGROUND/AIM
Acne vulgaris (AV) is a common inflammatory skin condition associated with psychological and social distress. Its pathogenesis involves factors such as sebaceous hypersecretion and colonization. Vitamin D plays a crucial role in the pathogenesis of various inflammatory skin disorders, including AV, due to its immunomodulatory effects and involvement in keratinocyte growth and maturity. However, adequate sun exposure is required for optimal vitamin D synthesis. Isotretinoin (IOS), a vitamin A derivative, is a commonly used medication for severe acne, acting by binding to retinoid receptors. It can also form heterodimers with vitamin D receptors, potentially increasing vitamin D catabolism. Previous studies examining the impact of oral IOS on serum vitamin D levels have yielded inconsistent results. Therefore, this study aimed to assess changes in 25-hydroxy (OH) vitamin D serum levels in individuals with severe AV before and after IOS treatment.
MATERIALS AND METHODS
One hundred patients with severe AV were enrolled, each receiving 0.75 mg/kg IOS treatment daily for 4 months. Serum 25 OH vitamin D levels were measured before, during, and after treatment.
RESULTS
This study found a significant increase in serum 25 OH vitamin D levels among patients with severe AV following IOS treatment (p < 0.001).
CONCLUSION
This study suggests that AV may negatively impact vitamin D synthesis, but IOS treatment appears to raise vitamin D serum levels in individuals with severe AV. Further research is needed to confirm the potential relationship between AV and vitamin D levels.
Topics: Humans; Isotretinoin; Acne Vulgaris; Vitamin D; Male; Female; Dermatologic Agents; Prospective Studies; Young Adult; Adult; Adolescent
PubMed: 38813517
DOI: 10.55730/1300-0144.5742 -
Turkish Journal of Medical Sciences 2023To compare the effectiveness of instrument-assisted soft tissue mobilization (IASTM) and extracorporeal shock wave therapy (ESWT) used in myofascial pain syndrome (MPS)... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND/AIM
To compare the effectiveness of instrument-assisted soft tissue mobilization (IASTM) and extracorporeal shock wave therapy (ESWT) used in myofascial pain syndrome (MPS) and to determine whether they are superior to conservative treatment (CT).
MATERIALS AND METHODS
A total of 42 female patients (aged 18-60 years) diagnosed with MPS were enrolled and randomly assigned to either the CT (n = 14), CT+IASTM (n = 14), or CT+ESWT group (n = 14). All of the groups received treatment for 3 weeks (CT: 5 sessions per week, 15 sessions in total, ESWT and IASTM: 2 sessions per week, 6 sessions in total). Neck stretching exercises were given to all of the patients as a home program. The pain intensity of the patients was determined using the visual analog scale (VAS). The pressure pain threshold (PPT) was measured with an algometer. Cervical joint range of motion (ROM) was measured with a cervical ROM (CROM) device. Pain, cervical disability, quality of life, and sleep disturbances were evaluated with the Neck Outcome Score (NOOS). Depression and anxiety parameters were evaluated with the Hospital Anxiety and Depression Scale (HADS). Evaluations were made before treatment and 3 days after the last treatment session.
RESULTS
The CT+IASTM group was more successful than the other groups in terms of pain intensity, PPT, and improvements in the ROM parameters (p < 0.05). No significant difference was found between the NOOS and HADS scores of the groups when the posttreatment changes were compared to pretreatment (p > 0.05).
CONCLUSIONS
All 3 of these treatments can be used to alleviate the negative effects of MPS. IASTM treatment can be preferred primarily in the creation of combined treatment programs for patients with ROM limitations and low PPTs.
Topics: Humans; Female; Adult; Extracorporeal Shockwave Therapy; Myofascial Pain Syndromes; Middle Aged; Young Adult; Treatment Outcome; Range of Motion, Articular; Adolescent; Pain Measurement; Quality of Life; Therapy, Soft Tissue
PubMed: 38813497
DOI: 10.55730/1300-0144.5753 -
EClinicalMedicine May 2024Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in . It presents with disproportionate short stature with a wide range of...
BACKGROUND
Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in . It presents with disproportionate short stature with a wide range of clinical severity. There are currently no approved medications to treat short stature in children with hypochondroplasia. Vosoritide is a C-type natriuretic peptide analog that was recently approved for improving growth in children with achondroplasia. We aimed to evaluate the safety and efficacy of vosoritide in children with hypochondroplasia.
METHODS
We conducted a single-arm, phase 2, open-label trial at a single centre in the USA and enrolled 26 children with hypochondroplasia. The trial consists of a 6-month observation period to establish a baseline annualized growth velocity followed by a 12-month intervention period during which vosoritide is administered daily via subcutaneous injection at a dose of 15 μg/kg/day. The trial's co-primary endpoints included the incidence of adverse events and the change from baseline in age-sex standardized annualized growth velocity and height standardized deviation score (SDS) after 12 months of treatment. This trial is registered with ClinicalTrials.gov (NCT04219007).
FINDINGS
Twenty-four participants with a mean age of 5.86 years received vosoritide therapy. The first participant was enrolled on August 4, 2020, and the final participant completed the 18-month trial on September 8, 2023. Vosoritide was well tolerated with no treatment-related serious adverse events. Injection site reactions occurred in 83.3% of participants. No participants discontinued therapy due to an adverse event. Annualized growth velocity increased by 2.26 standard deviations (SD) and height SDS increased by 0.36 SD during the treatment period versus the observation period. Hypochondroplasia specific height SDS increased by 0.38 SD. There was a 1.81 cm/year increase in absolute annualized growth velocity.
INTERPRETATION
Vosoritide was safe and effective in increasing growth velocity in children with hypochondroplasia. Efficacy was similar to what has been reported in children with achondroplasia.
FUNDING
This study was supported by an investigator-initiated grant from BioMarin Pharmaceutical.
PubMed: 38813446
DOI: 10.1016/j.eclinm.2024.102591 -
EClinicalMedicine May 2024Postpartum blues (PPB) is a frequent syndrome of sad mood, crying spells, anxiety, restlessness, reduced appetite, and irritability, typically peaking day 5 postpartum....
BACKGROUND
Postpartum blues (PPB) is a frequent syndrome of sad mood, crying spells, anxiety, restlessness, reduced appetite, and irritability, typically peaking day 5 postpartum. When severe, it greatly increases risk for later postpartum depression. This trial compared a dietary supplement to placebo on PPB severity. The supplement was designed to counter downstream effects of elevated monoamine oxidase A level, implicated in causing PPB.
METHODS
Participants recruited by advertisement from the Toronto region completed procedures at CAMH, Canada and/or participants' homes. Oral supplement or identical appearing relatively inert placebo were administered in randomised, double-blind fashion. Supplement was blueberry juice and extract given four times between nighttime day 3 and morning day 5 postpartum; tryptophan 2 g nighttime day 4 postpartum, and tyrosine 10 g morning day 5 postpartum. On day 5, depressed mood induction procedure (MIP) and postpartum blues were assessed. All data is presented (NCT03296956 closed, clinicaltrials.gov).
FINDINGS
Between January 2019 and December 2022, participants took supplement (n = 51) or placebo (n = 52). There was no significant effect on primary outcome MIP on visual analogue scale for depressed mood (mean difference = -0.39 mm, 95% CI: -6.42 to 5.65 mm). Stein Maternity Blues scores, exploratory PPB measure, was lower in the active group (effect size 0.62; median, interquartile range (IQR): active 2.00 (IQR 1, 4); placebo 4.00 (IQR 1.5, 6); regression with general linear model, supplement effect, β coefficient = -1.50 (95%: CI -2.60, -0.40), p = 0.008; effect of CES-D crying category before supplement, p = 0.03-0.00000023). Twenty-six and 40 different adverse events occurred within 25% and 42% of supplement and placebo cases respectively (Chi-Square, p = 0.06).
INTERPRETATION
The primary outcome was negative for effect on depressed mood induction, however the supplement moderately reduced PPB.
FUNDING
CAMH/Exeltis.
PubMed: 38813444
DOI: 10.1016/j.eclinm.2024.102593 -
Frontiers in Public Health 2024Light's non-visual effects on the biological clock, cognitive performance, alertness, and mental health are getting more recognized. These are primarily driven by blue...
INTRODUCTION
Light's non-visual effects on the biological clock, cognitive performance, alertness, and mental health are getting more recognized. These are primarily driven by blue light, which triggers specific retinal cells containing melanopsin. Traditionally, research on light has relied on correlated color temperature (CCT) as a metric of its biological influence, given that bluer light corresponds to higher Kelvin values. However, CCT proves to be an inadequate proxy of light's biological effects. A more precise metric is melanopic Equivalent Daylight Illuminance (mel-EDI), which aligns with melanopsin spectrum. Studies have reported positive cognitive impacts of blue-enriched white light. It's unclear if the mixed results are due to different mel-EDI levels since this factor wasn't assessed.
METHOD
Given recent recommendations from experts to aim for at least 250 mel-EDI exposure daily for cognitive benefits, our aim was to assess if a 50-minute exposure to LED light with 250 mel-EDI could enhance concentration and alertness, without affecting visual performance or comfort compared to conventional lighting producing around 150 mel-EDI. To ensure mel-EDI's impact, photopic lux levels were kept constant across conditions. Conditions were counterbalanced, parameters included subjective sleepiness (KSS; Karolinska Sleepiness Scale), concentration (d2-R test), visual performance (FrACT; Freiburg Visual Acuity and Contrast Test), general appreciation (VAS; Visual Analogous Scale), preferences and comfort (modified OLS; Office Lighting Survey).
RESULTS
The experimental light significantly reduced sleepiness ( = 0.03, Cohen's d = 0.42) and also decreased contrast sensitivity ( = 0.01, Cohen's d = 0.50). The conventional light was found to be more comfortable ( = 0.002, Cohen's d = 0.62), cheerful ( = 0.02, Cohen's d = 0.46) and pleasant ( = 0.005, Cohen's d = 0.55) while the experimental light was perceived as brighter ( = 0.004, Cohen's d = 0.58) and tended to be more stimulating ( = 0.10). Notably, there was a preference for conventional lighting ( = 0.004, Cohen's d=0.56) and concentration was equally improved in both conditions.
DISCUSSION
Despite the lack of further improvement in concentration from exposure to blue-enriched light, given the observed benefits in terms of vigilance, further research over an extended period would be justified. These findings could subsequently motivate cognitive optimization through lighting for workers that would benefit from artificial lighting such as in northern regions.
Topics: Humans; Lighting; Cognition; Male; Arousal; Female; Light; Adult; Young Adult; Color; White
PubMed: 38813427
DOI: 10.3389/fpubh.2024.1390614