Performance and failure of right ventricle to pulmonary artery conduit in congenital heart disease.

INTRODUCTION: Surgical implantation of a right ventricle to pulmonary artery (RV-PA) conduit is an important component of congenital heart disease (CHD) surgery but with limited durability leading to re-intervention. Current single-center, retrospective, cohort study is reporting results of surgically implanted RV-PA conduits in a consecutive series of children and adults with CHD. METHODS: Patients with CHD referred for RV-PA conduits surgical implantation (October 1997 and January 2022) have been included. Primary outcome was conduit failure defined as peak gradient above 64mmHg/severe regurgitation/need for conduit-related interventions. Longitudinal echocardiographic studies were available for mixed-effect linear regression analysis. RESULTS: Two-hundred and fifty-two patients were initially included. One hundred and forty-nine patients were elegible for follow-up data collection. After a median follow-up time of 49 months the primary study endpoint occurred in 44 (29%) patients. Multivariable Cox regression model identified adult age (>18 years) at implantation and pulmonary homograft as protective factors (HR 0.11, 95% CI 0.02-0.47 and HR 0.34, 95% CI 0.16-0.74, respectively). Fever within 7 days of surgical conduit implantation was a risk factor for early (within 24 months) failure (OR 4.29, 95% CI 1.41-13.01). Longterm use of oral anticoagulant was independently associated with slower progression of peak echocardiographic gradient across conduits (mixed effect linear regression p-value 0.027). CONCLUSION: In patients with CHD, surgically implanted RV-PA conduit failure is faster in children and after non-homograft conduit implantation. Early fever after surgery is a strong risk factor for early failure. Longterm anticoagulation seems to exert a protective effect.

Fluorine-18 FDG PET/CT and New NIMS Grading System for Chemotherapy Response in Breast Cancer.

Background: Positron emission tomography with computed tomography (PET-CT) using fluorine 18-fluorodeoxyglucose (F-18 FDG) is increasingly used to stage patients with locally advanced breast cancer and for assessing treatment response after neoadjuvant chemotherapy (NACT). Aims and Objectives: The aim of the study was to assess the correlation between PET-CT parameters and pathologic response of breast primary after NACT in breast cancer patients and to devise a grading system called NIMS grading system for response assessment using PET quantitative parameters. Materials and Methods: 55 patients who underwent F-18 FDG PET-CT before starting the therapy and again after completion of therapy were identified and included in the study. The clinical data and the histopathologic findings were recorded. All the patients received chemotherapy followed by surgery with axillary lymph node dissection. The PET-CT results were interpreted both qualitatively by visual analysis and quantitatively by estimating maximum Standardized uptake values(SUVmax) and other parameters - SUVmean, SUL, SUVBSA, Metabolic tumor volume (MTV) and Total lesion glycolysis (TLG). Results: The sensitivity and specificity of F-18 FDG PET-CT to detect the residual disease after neoadjuvant chemotherapy was 75.6% & 92.8% respectively. Differences between complete response and residual disease were significant for ΔSUVmax(p=0.005), ΔSUVmean(p=0.006), ΔSUL (0.005) and ΔSUVBSA(0.004), while ΔMTV and ΔTLG were not significantly different between the two groups. The new NIMS grading system included scoring of ΔSUVmax, ΔSUVBSA, ΔTLG and ΔMTV on scale of 1 to 4 and correlated well with PERCIST criteria. Conclusion: F-18 FDG PET-CT had a good accuracy in the detection of residual disease after completion of NACT. Pre chemotherapy PET-CT is not adequate to predict the response of primary tumour to chemotherapy. However, changes in the values of various PET-CT parameters are a sensitive tool to assess the response to chemotherapy. The new grading system is easy to use and showed good correlation to PERCIST.

Cardiac output in patients with small annuli undergoing transcatheter aortic valve implantation with self-expanding versus balloon expandable valve (COPS-TAVI).

BACKGROUND: There is limited data on cardiac output in patients with small aortic annuli undergoing trans-catheter aortic valve implantation (TAVI) according to the implanted platform of balloon-expandable (BEV) compared to self-expanding valves (SEV). METHODS: This is a retrospective analysis of consecutive patients with severe aortic stenosis and small annuli who underwent successful TAVI. Cardiac output was measured using echocardiography within 4 weeks following TAVI. Data were recorded and analysed by an experienced operator who was not aware of the type of the implanted valve. RESULTS: 138 patients were included in the analysis, of whom 57 % underwent TAVI with BEV. Clinical and echocardiographic characteristics were comparable between the two platforms, except for more frequent previous cardiac surgery and smaller indexed aortic valve in the BEV group. There was no relationship between computed tomography-derived aortic annulus area and cardiac output post TAVI. When compared to patients who underwent TAVI with BEV, those with SEV had larger cardiac output [mean difference - 0.50 l/min, 95 % CI (-0.99, -0.01)] and cardiac index [mean difference - 0.20 l/min/m2, 95 % CI (-0.47, 0.07)], although the latter did not reach statistical significance. Unlike patients with small body surface area, in those with large body surface area both cardiac output and cardiac index were statistically larger in patients who underwent SEV compared to BEV. CONCLUSION: Cardiac output, as measured by echocardiography, was larger in patients with small annuli who underwent TAVI procedure with SEV compared to BEV. Such difference was more evident in patients with large body surface area.

Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.

OBJECTIVES: The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. METHODS: We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. RESULTS: Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. CONCLUSIONS: In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.

Prediction of the 10-year incidence of type 2 diabetes mellitus based on advanced anthropometric indices using machine learning methods in the Iranian population.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a growing chronic disease that can lead to disability and early death. This study aimed to establish a predictive model for the 10-year incidence of T2DM based on novel anthropometric indices. METHODS: This was a prospective cohort study comparing people with (n = 1256) and without (n = 5193) diabetes mellitus in phase II of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. The association of several anthropometric indices in phase I, including Body Mass Index (BMI), Body Adiposity Index (BAI), Abdominal Volume Index (AVI), Visceral Adiposity Index (VAI), Weight-Adjusted-Waist Index (WWI), Body Roundness Index (BRI), Body Surface Area (BSA), Conicity Index (C-Index) and Lipid Accumulation Product (LAP) with T2DM incidence (in phase II) were examined; using Logistic Regression (LR) and Decision Tree (DT) analysis. RESULTS: BMI followed by VAI and LAP were the best predictors of T2DM incidence. Participants with BMI < 21.25 kg/m2 and VAI ≤ 5.9 had a lower chance of diabetes than those with higher BMI and VAI levels (0.033 vs. 0.967 incident rate). For BMI > 25 kg/m2, the chance of diabetes rapidly increased (OR = 2.27). CONCLUSIONS: BMI, VAI, and LAP were the best predictors of T2DM incidence.

New limits proposed for the management of non-mutagenic impurities.

Multiple international guidelines exist that describe both quality and safety considerations for the control of the broad spectrum of impurities inherent to drug substance and product manufacturing processes. However, regarding non-mutagenic impurities (NMI) the most relevant ICH Q3A/B guidelines are not applicable during early phases of drug development leading to confusion about acceptable limits at this stage. Thus, there is need for more flexible approaches that ensure that patient safety remains paramount, while taking into consideration the limited duration of exposure. An EFPIA survey, which collected quantitative data from different types of studies applied to qualify impurities in accordance with ICH Q3A, shows that no toxicities could be attributed to any of the 467 impurities at any tested level in vivo. This data combined with earlier published toxicological datasets encompassing drug substances and intermediates, food related substances and chemicals provide convincing evidence that for NMIs, the application of a generic 5 mg/day limit for an exposure duration <6 months, and a 1 mg/day generic limit for life-long exposure, provides sufficient margins to ensure patient safety. Hence, application of these absolute limits to trigger qualification studies (instead of the relative limits described in Q3A/B), is considered warranted. This approach will prevent conduct of unnecessary dedicated impurity qualification studies and the resulting use of animals.

Baricitinib Improvement Across Regions in Atopic Dermatitis Patients with Baseline Body Surface Area up to 40% and Severe Itch.

INTRODUCTION: Patients with moderate-to-severe atopic dermatitis (AD) who are most likely to respond to the Janus kinase (JAK) 1/2 inhibitor baricitinib (BARI) are known to have an impacted body surface area (BSA) ≤ 40% and severe itch (numerical rating scale [NRS] ≥ 7], collectively termed 'BARI itch-dominant' patients. Our objective is to build on our previous work by providing a body region-specific, clinical characterization of the BARI itch-dominant patient at baseline and their response to BARI 4 mg. METHODS: BREEZE-AD7 was a phase 3 trial in adults with moderate-to-severe AD receiving placebo or 2 mg or 4 mg BARI in combination with topical corticosteroids. Assessing only data from BARI itch-dominant patients, we summarized the baseline characteristics and conducted body region-specific analyses on Eczema Area and Severity Index (EASI) data in order to report the response to placebo versus BARI 4 mg within this patient subtype. RESULTS: BARI 4 mg was highly effective across all body regions; at week 16, 75% improvement was seen in EASI scores (EASI75), and response rates with BARI 4 mg (head/neck, 58.3%; trunk, 69.2%; upper extremities, 61.5%; lower extremities, 87.5%) all exceeded those with placebo (head/neck: 37.5%; trunk, 40.6%; upper extremities, 18.8%; lower extremities, 40.6%) as well as the overall EASI75 rates of the intent-to-treat (ITT) population (BARI, 48.0%; placebo, 23.0%). At baseline, most BARI itch-dominant patients presented with involvement of all regions (mean regional BSA 22.7%-40.3%), highest in the head and neck, mean EASI region scores of 15.7-24.0, and considerably severe sign ratings (mean EASI sub-scores: 1.4-2.3, out of 3), especially for erythema. CONCLUSION: BARI itch-dominant patients exhibit AD involvement across all body regions and considerable sign severity, especially erythema. In response to BARI 4 mg, EASI quickly improved across regions, substantially more so in this subtype than in the ITT population.

Sex bias in prediction and diagnosis of cardiac surgery associated acute kidney injury.

BACKGROUND: Female sex has been recognized as a risk factor for cardiac surgery associated acute kidney injury (CS-AKI). The current study sought to evaluate whether female sex is a risk factor for CS-AKI, or modifies the association of peri-operative change in serum creatinine with CS-AKI. METHODS: Observational study of adult patients undergoing cardiac surgery between 2000 and 2019 in a single U.S. center. The main variable of interest was registered patient sex, identified from electronic medical records. The main outcome was CS-AKI within 2 weeks of surgery. RESULTS: Of 58526 patients, 19353 (33%) were female; 12934 (22%) incurred AKI based on ≥ 0.3 mg/dL or ≥ 50% rise in serum creatinine (any AKI), 3320 (5.7%) had moderate to severe AKI, and 1018 (1.7%) required dialysis within 2 weeks of surgery. Female sex was associated with higher risk for AKI in models that were based on preoperative serum creatinine (OR, 1.35; 95% CI, 1.29-1.42), and lower risk with the use of estimated glomerular filtration, (OR, 0.90; 95% CI, 0.86-0.95). The risk for moderate to severe CS-AKI for a given immediate peri-operative change in serum creatinine was higher in female compared to male patients (p < .0001 and p < .0001 for non-linearity), and the association was modified by pre-operative kidney function (p < .0001 for interaction). CONCLUSIONS: The association of patient sex with CS-AKI and its direction was dependent on the operational definition of pre-operative kidney function, and differential outcome misclassification due to AKI defined by absolute change in serum creatinine.

Ixekizumab Demonstrates Rapid and Consistent Efficacy for Patients with Psoriatic Arthritis, Regardless of Psoriasis Severity.

INTRODUCTION: Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week 24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or psoriasis at baseline. METHODS: This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W). Efficacy outcomes were analyzed through week 24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA < 3%, moderate = 3% ≤ BSA ≤ 10%, severe = BSA > 10%. The primary outcomes assessed were the proportion of patients achieving American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. Secondary outcomes included musculoskeletal, disease activity, skin and nail, and health-related quality-of-life measures. RESULTS: Similar proportions of patients achieved ACR20/ACR50/ACR70 over time across all severity subgroups and treatment arms. More than one-third of IXE-treated patients achieved ACR20 at week 4, or ACR50 at week 24, with no significant differences according to psoriasis severity at baseline. Disease activity outcomes were similar through week 24 with both IXEQ4W and IXEQ2W, regardless of psoriasis severity at baseline. There were no significant differences over 24 weeks in the proportions of IXE-treated patients with mild, moderate, or severe baseline psoriasis who achieved Minimal Disease Activity (MDA). Across all severity subgroups, IXE demonstrated Psoriasis Area Severity Index 100 response as early as week 4, and approximately one-third of IXE-treated patients achieved total skin clearance at week 24. CONCLUSION: IXE demonstrated rapid and consistent efficacy in joint, skin, and nail for patients with PsA, regardless of baseline psoriasis severity. TRIAL REGISTRATION: SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295).

Body surface area is positively associated with ankle-brachial index.

BACKGROUND: Ankle-brachial index (ABI) measurement is a widely used diagnostic test for lower extremity artery disease. Previously, a larger body surface area (BSA) has been associated with lower blood pressure and lower 2-h post-load glucose concentrations in the oral glucose tolerance test. Our aim was to evaluate whether BSA has an impact on ABI and the prevalence of lower ABI values. METHODS: ABI measurements were performed on 972 subjects aged 45 to 70 years at high cardiovascular disease (CVD) risk. Subjects with previously diagnosed kidney disease, CVD, and diabetes were excluded. Their BSA was calculated by the Mosteller formula. Study subjects were divided into five BSA levels corresponding to 12.5th, 25th, 25th, 25th, and 12.5th percentiles of the total distribution. Effect modification by BSA in ABI between sexes was derived from a four-knot restricted cubic splines regression model. RESULTS: After adjustments for age, sex, pulse pressure, glucose regulation, waist circumference, alcohol intake, smoking status, leisure-time physical activity and medication, BSA level had a positive linear relationship with ABI (p for linearity <0.001). When BSA was less than 2.0 m2, there was no difference between the sexes, but when BSA was higher than 2.0 m2, men had higher ABI. CONCLUSION: BSA shows a positive linear relationship with ABI in CVD risk subjects without manifested CVD. The difference in ABI between men and women is modified by BSA and is appreciable when BSA is larger than 2.0 m2.

Anthropometric measures of obesity in patients with knee joint pathology: Body surface area versus body mass index.

BACKGROUND: Obesity is quantified using body mass index. Body surface area may provide a superior and more anthropometric method of quantifying obesity in patients with musculoskeletal knee disease. This study compares the effect of weight, height, age and gender on body mass index and body surface area in a population with orthopaedic knee disease. METHODS: An observational cohort study was conducted of patients presenting with musculoskeletal knee disease. Associations between body mass index, body surface area, age, gender, height, weight and operative versus non-operative management were analysed. RESULTS: A total of 151 patients were included. Body surface area was more strongly correlated to weight than body mass index (r = 0.98, p < 0.001 versus r = 0.84, p < 0.001). Body surface area also reflects height which body mass index under presents (r = 0.65, p < 0.001 versus r = -0.08, p = 0.35). Body mass index and body surface area were correlated with one another (r = 0.70, p < 0.001). Age was inversely correlated with body surface area (r = -0.20, p = 0.013) but not body mass index (r = 0.05, p = 0.585). Body mass index did not differ between males and females (30.1 versus 30.9, p = 0.37); however, BSA scores were significantly higher in males than females (2.11 versus 1.91, p < 0.001). Neither body surface area nor body mass index scores influenced operative versus non-operative treatment. CONCLUSION: Body surface area could be a useful alternative to body mass index when considering obesity in patients with musculoskeletal knee pathology. Body surface area better reflects the effects of height, weight, age and gender than body mass index.

Body surface area is a predictor of 90-day all-cause mortality in critically ill patients with acute kidney injury.

OBJECTIVE: To clarify the prognosis effect between body surface area (BSA) and patients with acute kidney injury (AKI), we attempted to analyze the association between BSA and 90-day all-cause mortality in critically ill patients with AKI. METHODS: Clinical data of 9195 critically ill patients with AKI were retrieved from the Medical Information Mart for Intensive Care III database were then retrospectively analyzed. BSA were calculated using the Mosteller formula. We analyzed the correlation between BSA and 90-day all-cause mortality in critically ill patients with AKI based on Kaplan-Meier curve analysis and adjusted Cox regression model. RESULTS: Of the 9195 critically ill patients with AKI, there were 3778 (41.1%) female patients and 2001 90-day all-cause deaths (female: 22.2%, male: 21.5%). Kaplan-Meier curve analysis revealed that a lower body surface area indicated a higher 90-day all-cause mortality in both male and female patients with AKI (log-rank P < 0.001). Cox regression model showed that a higher BSA was independently correlated with a lower 90-day all-cause mortality (female: hazard ratio=0.657, 95% confidence interval: 0.550-0.784, P < 0.001; male: hazard ratio=0.655, 95% confidence interval: 0.565-0.760, P < 0.001). CONCLUSIONS: BSA was negatively correlated with 90-day all-cause mortality in critically ill patients with AKI. BSA can therefore be used as a prognostic indicator for poor outcomes in critically ill patients with AKI.

Sex Bias in Prediction and Diagnosis of Cardiac Surgery Associated Acute Kidney Injury.

Background: Female sex has been recognized as a risk factor for cardiac surgery associated acute kidney injury (CS-AKI). The current study sought to evaluate whether female sex is a risk factor for CS-AKI, or modifies the association of peri-operative change in serum creatinine with CS-AKI. Methods: Observational study of adult patients undergoing cardiac surgery between 2000 and 2019 in a single U.S. center. The main variable of interest was registered patient sex, identified from electronic medical records. The main outcome was CS-AKI within 2 weeks of surgery. Results: Of 58526 patients, 19353 (33%) were female; 12934 (22%) incurred AKI based on ≥ 0.3 mg/dL or ≥ 50% rise in serum creatinine (any AKI), 3320 (5.7%) had moderate to severe AKI, and 1018 (1.7%) required dialysis within 2 weeks of surgery. Female sex was associated with higher risk for AKI in models that were based on preoperative serum creatinine (OR, 1.35; 95% CI, 1.29-1.42), and lower risk with the use of estimated glomerular filtration, (OR, 0.90; 95% CI, 0.86-0.95). The risk for moderate to severe CS-AKI for a given immediate peri-operative change in serum creatinine was higher in female compared to male patients (p < .0001 and p < .0001 for non-linearity), and the association was modified by pre-operative kidney function (p < .0001 for interaction). Conclusions: The association of patient sex with CS-AKI and its direction was dependent on the operational definition of pre-operative kidney function, and differential outcome misclassification due to AKI defined by absolute change in serum creatinine.

An improvement of body surface area formulas using the 3D scanning technique.

OBJECTIVES: Body surface area (BSA) is one of the major parameters used in several medical fields. However, there are concerns raised about its usefulness, mostly due to the ambiguity of its estimation. MATERIAL AND METHODS: Authors have conducted a voluntary study to investigate BSA distribution and estimation in a group of 179 adult people of various sex, age, and physique. Here, there is provided an extended analysis of the majority of known BSA formulas. Furthermore, it was supplement with a comparison with the authors' propositions of enhanced formulas coefficients for known formulas models as well as with new power models based on an increased number of anthropometric data. RESULTS: Introduction of the enhanced formulas coefficients cause a reduction of at least 30.5% in mean absolute error and 21.1% in maximum error in comparison with their known counterparts. CONCLUSIONS: In the context of the analysis presented it can be stated that the development of a single universal body surface area formula, based on a small number of state variables, is not possible. Therefore, it is necessary and justified to search for new estimation models that allow for quick and accurate calculation of body surface area for the entire population, regardless of individual body variations. The new formulas presented are such an alternative, which achieves better results than the previously known methods. Int J Occup Med Environ Health. 2024;37(2):205-19.

Prediction of fat-free mass from body surface area in young basketball players.

BACKGROUND: Fat Free Mass (FFM) is an important and essential indicator in various sports populations, since greater muscle and bone mass generates greater strength, endurance and speed in athletes. OBJECTIVE: The purpose of the study was to validate Body Surface Area (BSA) as an anthropometric indicator to estimate FFM in young basketball players. METHODS: A descriptive cross-sectional study was carried out in 105 male basketball players of the Brazilian Basketball Confederation of Sao Paulo (Campinas), Brazil. The age range was 11 to 15 years. Weight and height were evaluated. BSA, body mass index (BMI) and maturity status (MS) were calculated. Total body scanning was performed by dual X-ray absorptiometry (DXA). The components were extracted: Fat mass (FM), Fat free mass (FFM), percentage of fat mass (%FM) and bone mass (BM). The data were analyzed using the correlation coefficient of concordance (CCC) in terms of precision and accuracy. RESULTS: Three regression equations were generated: equation 1 had age and body weight as predictors [FFM= -30.059+(2.926*age)+(0.625*Weight)] (R2 = 92%, precision = 0.96 and accuracy = 0.99), equation 2 used age and BSA [FFM=-45.719+(1.934*age)+(39.388*BSA)] (R2 = 94%, precision = 0.97 and accuracy = 0.99) and equation 3 was based on APHV and BSA [FFM=-15.284+(1.765*APHV)+(37.610*(BSA)] (R2 = 94%, precision = 0.96 and accuracy = 0.99). CONCLUSIONS: The results suggest the use of anthropometric equation using decimal age and BSA to estimate FFM in young basketball players. This new method developed can be used to design, evaluate and control training programs and monitor the weight status of athletes.

Comparing Achievement of National Psoriasis Foundation Treatment Targets among Patients with Plaque Psoriasis Treated with Ixekizumab versus Other Biologics in Clinical and Real-World Studies.

INTRODUCTION: The National Psoriasis Foundation (NPF) recommends evaluating patient response to treatment at week 12, with a target response of ≤ 1% body surface area (BSA) affected by plaque psoriasis and an acceptable response of BSA ≤ 3% or ≥ 75% improvement. This post hoc analysis compared the achievement of NPF target and acceptable responses for ixekizumab (IXE) versus other biologics. METHODS: Outcomes were evaluated at week 12 for patients with moderate-to-severe plaque psoriasis from four head-to-head randomized clinical trials (RCTs; UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) and one real-world prospective observational study (Psoriasis Study of Health Outcomes; PSoHO). RCT patients were treated with IXE or etanercept (ETN; UNCOVER-2/3), guselkumab (GUS; IXORA-R), or ustekinumab (UST; IXORA-S). PSoHO patients were treated with anti-interleukin (IL)-17A biologics (IXE, secukinumab, SEC) and other approved biologics for the treatment of plaque psoriasis. Patients with missing outcomes were imputed as non-responder imputation. For RCT data, statistical comparisons between treatment groups were performed using Fisher's exact test with no multiplicity adjustments. For real-world data, adjusted comparative analyses were performed using frequentist model averaging (FMA) and reported as odds ratio (OR). RESULTS: Across the four head-to-head clinical trials analyzed, significantly higher proportions of patients achieved target and acceptable responses at week 12 with IXE versus ETN, GUS, or UST. Likewise, the proportion of PSoHO patients achieving target and acceptable response at week 12 was higher with IXE compared with other individual biologics. Adjusted comparative analyses showed that IXE had significantly greater odds of target and acceptable response at week 12 versus SEC, GUS, risankizumab (RIS), adalimumab (ADA), UST, and tildrakizumab (TILD) and numerically greater odds of target and acceptable response at week 12 versus brodalumab (BROD). CONCLUSION: Across both clinical studies and real-world settings, more patients treated with IXE achieved NPF target and acceptable responses at week 12 compared with those treated with other biologics. TRIAL REGISTRATION: UNCOVER-2 (NCT01597245); UNCOVER-3 (NCT01646177); IXORA-R (NCT03573323); IXORA-S (NCT02561806); PSoHO (EUPAS24207).

Patients with infusion-related reactions on fixed-dose rituximab treatment have higher body surface area than those without infusion-related reactions in adults with frequently relapsing minimal change nephrotic syndrome: a retrospective study.

BACKGROUND: Infusion-related reactions (IRRs) are major side effects of rituximab administration. Male sex, high body weight, body surface area (BSA), and body mass index are predictive markers of rituximab-induced IRRs. However, as rituximab was not administered at a fixed dosage in a previous study, whether a higher dosage or factors associated with a larger physique are more strongly associated with rituximab-induced IRRs is unknown. MAIN BODY: Thirteen adults with frequently relapsing minimal change nephrotic syndrome (MCNS) who received an initial rituximab dose of 500 mg between September 2015 and November 2022 were retrospectively evaluated. Data on IRRs were collected from medical records. The incidence of rituximab-induced IRRs was 38.5% (5/13). The IRR group had a significantly higher BSA than the non-IRR group (median, 1.86 vs. 1.48 m2; p = 0.045). Additionally, rituximab dosage normalized by BSA in the IRR group was significantly lower than that in the non-IRR group (median, 268.8 vs. 337.9 mg/m2; p = 0.045). CONCLUSIONS: Our study revealed that adults with frequently relapsing MCNS who experienced IRRs tend to have a higher BSA, even with fixed-dose rituximab treatment. Therefore, when patients with higher BSA receive rituximab treatment, clinicians should be careful about monitoring patient condition whether the dosage is fixed or not.

High Ferritin Is Not Needed in Hemodialysis Patients: A Retrospective Study of Total Body Iron and Oral Iron Replacement Therapy.

In vivo iron levels can be adjusted through intestinal iron absorption to be maintained at a suitable level; however, optimal iron levels in hemodialysis (HD) patients are unclear. In this study, we investigated total body iron (TBI), calculated as the sum of red blood cell (RBC) iron and iron stores, during courses of low-dose oral iron replacement therapy, and evaluated in vivo iron sufficiency and its indicators in HD patients. We analyzed data on 105 courses of low-dose iron replacement therapy administered to 83 patients on maintenance HD over 7 months. We evaluated changes in TBI, RBC iron, and iron stores from the initiation of treatment to month 7 in two groups of patients, namely, iron-therapy responders and non-responders. TBI showed significant increases until month 4 and plateaued thereafter in iron-therapy responders, and tended to increase and then reached a similar plateau in non-responders (month 7: 1900 ± 447 vs. 1900 ± 408 mg). Steady-state TBI was strongly correlated with body surface area (y = 1628.6x - 791.91, R2 = 0.88, p < 0.001). We observed constant TBI during oral iron replacement therapy suggesting the activation of a "mucosal block". The results suggest that body surface area has utility for estimating the required TBI with regression equations.

Pharmacokinetic Analysis of Levodropropizine and Its Potential Therapeutic Advantages Considering Eosinophil Levels and Clinical Indications.

Levodropropizine is a non-narcotic, non-centrally acting antitussive that inhibits the cough reflex triggered by neuropeptides. Despite the active clinical application of levodropropizine, the exploration of its inter-individual pharmacokinetic diversity and of factors that can interpret it is lacking. The purpose of this study was to explore effective covariates associated with variation in the pharmacokinetics of levodropropizine within the population and to perform an interpretation of covariate correlations from a therapeutic perspective. The results of a levodropropizine clinical trial conducted on 40 healthy Korean men were used in this pharmacokinetic analysis, and the calculated pharmacokinetic and physiochemical parameters were screened for effective correlations between factors through heatmap and linear regression analysis. Along with basic compartmental modeling, a correlation analysis was performed between the model-estimated parameter values and the discovered effective candidate covariates for levodropropizine, and the degree of toxicity and safety during the clinical trial of levodropropizine was quantitatively monitored, targeting the hepatotoxicity screening panel. As a result, eosinophil level and body surface area (BSA) were explored as significant (p-value < 0.05) physiochemical parameters associated with the pharmacokinetic diversity of levodropropizine. Specifically, it was confirmed that as eosinophil level and BSA increased, levodropropizine plasma exposure increased and decreased, respectively. Interestingly, changes in an individual's plasma exposure to levodropropizine depending on eosinophil levels could be interpreted as a therapeutic advantage based on pharmacokinetic benefits linked to the clinical indications for levodropropizine. This study presents effective candidate covariates that can explain the inter-individual pharmacokinetic variability of levodropropizine and provides a useful perspective on the first-line choice of levodropropizine in the treatment of inflammatory respiratory diseases.