Patient Dose Research Articles

Comparative evaluation of image quality between virtual grid and grid portable radiographic systems

Purpose. Virtual Grid (VG) is an image processing technique designed to address scattered radiation from radiographic systems without a physical grid. It aims to eliminate artifacts caused by grid misalignment and enhance radiographic workflow efficiency. We intend to evaluate image quality between Virtual Grid and grid-based radiographic systems across various patient thicknesses. Methods. A Fujifilm Virtual Grid and GE AMX-4 portable radiographic system was used. Image quality was assessed using MTF, NPS, LCR, and CNR. MTF calculations employed an edge-device method with a 0.1 mmCu sheet. For NPS evaluation, uniform images were acquired with multiple 30 × 30 cm solid water blocks (2 cm thick), overlaid in 2 cm increments to simulate patient sizes from 2cm to 40 cm. LCR and CNR were evaluated using a CIRS test plate with 9-hole depths for a hole diameter of 0.375’. The test object was placed on top of the detector then water blocks, while maintaining the same SID, beam quality, and exposure between the units. Visual assessments were conducted by four readers, quantifying perceived hole numbers. The weighted Cohen’s Kappa and Welch’s T-test were utilized for statistical analysis. Results. At 80% MTF, VG exhibited high contrast resolution of 1.1 l p/mm compared to 1.2 l p/mm for the grid system. VG demonstrated lower noise levels across all frequencies for equivalent patient thicknesses. Welch’s T-test indicated no significant differences in LCR (P = 0.31) and CNR (P = 0.34) between the systems. However, qualitative observation demonstrated VG’s better low contrast response for patient sizes ≥10 cm. The average weighted Cohen’s Kappa value was 0.78. Conclusion. This work indicates the Virtual Grid technology can effectively mitigate scattered radiation to improve granularity and low-contrast resolution in an image compared to a grid system. Furthermore, it can potentially reduce patient dose.

2058: prospective correlation research on shoulder radiation dose and impairment in breast cancer patients

2058: prospective correlation research on shoulder radiation dose and impairment in breast cancer patients

Co-amorphous systems of sulfasalazine with matrine-type alkaloids: Enhanced solubility behaviors and synergistic therapeutic potential

Sulfasalazine (SULF), a sulfonamide antibiotic, has been utilized in the treatment of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) since its discovery. However, its poor water solubility causes the high daily doses (1–––3 g) for patients, which may lead to the intolerable toxic and side effects for their lifelong treatment for RA and IBD. In this work, two water-soluble natural anti-inflammatory alkaloids, matrine (MAR) and sophoridine (SPD), were employed to construct the co-amorphous systems of SULF for addressing its solubility issue. These newly obtained co-amorphous forms of SULF were comprehensively characterized by powder X-ray diffraction (PXRD), temperature-modulated differential scanning calorimetry (mDSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). We also investigated their dissolution behavior, including powder dissolution, in vitro release, and intrinsic dissolution rate. Both co-amorphous systems exhibited superior dissolution performance compared to crystalline SULF. The underlying mechanism responsible for the enhanced dissolution behaviors in co-amorphous systems were also elucidated. These mechanisms include the inhibition of nucleation, complexation, increased hydrophilicity, and robust intermolecular interactions in aqueous solutions. Importantly, these co-amorphous systems demonstrated satisfactory physical stability under various storage conditions. Network pharmacological analysis was utilized to investigate the potential therapeutic targets of both co-amorphous systems against RA, revealing similar yet distinct multi-target synergistic therapeutic mechanisms in the treatment of this condition. Our study suggests these drug-drug co-amorphous systems hold promise for optimizing SULF dosage in the future and providing a potential drug combination strategy.

Median effective dose of spinal ropivacaine in combined spinal and epidural anesthesia for emergency cesarean delivery following failed vaginal delivery with epidural labor analgesia: a single-blind, sequential dose-finding study.

This study aimed to estimate the median effective dose of intrathecal isobaric ropivacaine without opioid required for adequate cesarean delivery anesthesia after epidural labor analgesia. Patients aged 20-40years with American Society of Anesthesiology scores of I-II, body mass index ≤ 36, who underwent emergency cesarean delivery after failed vaginal delivery with epidural analgesia of a duration ≤ 6h were included in the study. After removal of the epidural used for labor analgesia, a new combined spinal epidural was performed, and a dose of intrathecal isobaric ropivacaine without opioid was administered. The dose was determined using up-down methodology, with the starting patient's dose set to 12mg. Adequate anesthesia, defined as a pinprick level no lower than T6 at 5min after ropivacaine administration, resulted in the next patient receiving a dose of ropivacaine 1mg higher, and inadequate anesthesia 1mg lower. The primary outcome was the median (95% confidence interval (CI)) dose of spinal ropivacaine required for adequate cesarean delivery anesthesia. Of the 46 patients included in the study, 40 were analyzed. The median spinal ropivacaine dose was 8.11mg (95% CI 7.29-8.93mg) by the Dixon and Mood method and 8.06mg (95% CI 6.93-9.00mg) by isotonic regression. Two patients had high spinal anesthesia. Our findings suggest that for 50% of patients undergoing cesarean delivery after failed vaginal delivery with epidural analgesia, an 8-mg spinal dose of isobaric ropivacaine without opioid provides an anesthesia level no lower than T6 at 5min.

The determination of coefficients for size specific effective dose for adult and pediatric patients undergoing routine computed tomography examinations.

The effective dose resulting from computed tomography (CT) scans provides an assessment of the risk associated with stochastic effects but does not account for the patient's size. Advances in Monte Carlo simulations offer the potential to obtain organ dose data from phantoms of varying stature, enabling derivation of a size-specific effective doses (SEDs) representing doses to individual patients. This study aimed to compute size-specific k-conversion factors for SED in routine CT examinations for adult and pediatric patients of different sizes. Radiation interactions were simulated for adult and pediatric phantom models of various sizes using National Cancer Institute CT version 3.0.20211123. Subsequent calculations of SED were performed, and coefficients for SED were derived, considering the variations in body sizes. The results revealed a strong correlation between effective diameter and weight, observed with size-specific k-conversion factors for adult and pediatric phantoms, respectively. While size-specific k-conversion factors for CT brain remained constant in adults, values for pediatric cases varied. When using the tube current modulation (TCM) system, size-specific k-conversion factors increased in larger phantoms and decreased in smaller ones. The extent of this increase or decrease correlated with the set TCM strength. This study provides coefficients for estimating SEDs in routine CT exams. Software utilizing look-up tables of coefficients can be used to provide dose information for CT scanners at local hospitals, offering guidance to practitioners on doses to individual patients and improving radiation risk awareness in clinical practice.

Optimal weight-based epinephrine dosing for patients with a low likelihood of survival following out-of-hospital cardiac arrest.

Cardiac arrest patients presenting with non-shockable rhythms have a low probability of survival, and epinephrine is one of the few pharmaceutical options for this group. The recommended 1.0mg adult dose is extrapolated from early animal studies and lacks adjustment for patient weight. Although several prior studies have investigated "low-" and "high-" dose epinephrine, none have identified a benefit to either strategy. To identify an optimal weight-based epinephrine dose for return-of-spontaneous-circulation (ROSC) after a single bolus among patients with low likelihood of survival. Included were adult patients who experienced a witnessed, non-traumatic out-of-hospital cardiac arrest prior to EMS arrival. Patients with shockable presenting rhythms or receiving bystander CPR were excluded. The AUROC was used to assess the predictive value of epinephrine dose (mg/kg) for ROSC following a single bolus. From the ROC curve, the optimal threshold dosage (OTD) was determined using the Youden Index. A logistic regression model calculated the adjusted odds ratio of OTD on ROSC. A total of 2,463 patients met inclusion criteria, of which 190 (7.7%) attained ROSC after the first epinephrine administration. The dosage AUROC for ROSC was 0.603 (p < 0.01). As calculated by the Youden index, the OTD was 0.013mg/kg. Patients receiving ≥ OTD were more likely to attain ROSC after a single epinephrine bolus (OR = 2.25,p < 0.001). Among patients with a low likelihood of survival, the optimal dose of epinephrine for attaining ROSC with a single bolus of epinephrine was 0.013mg/kg. These findings should inspire further investigation into optimal dosing strategies for epinephrine.

Pharmacokinetic and Pharmacodynamic Interactions of Momordica charantia extract with Glibenclamide in Streptozotocin induced Diabetic rats

Diabetes mellitus (DM) has emerged as a leading global health problem. Diabetes is estimated to affect 425 million adults globally. Majority of diabetic patients take herbal medicines as supplement for the treatment of diabetes. The combined use of herbs and modern synthetic medicine has increased the possibility of pharmacokinetic (PK) and pharmacodynamic (PD) interactions. Momordica charantia (MC) commonly known as bitter melon/bitter gourd, is globally marketed for treatment of diabetes. Many diabetic patients consume MC extract along with antidiabetic drugs for better therapeutic effect with or without knowledge of health care provider.The current study evaluated PKPD herb-interaction of MC extract with glibenclamide (GLB) following oral administration either alone or in combination with MC extract for 28-consequative days. MC extract co-administratioin showed increased plasma exposure of GLB on Day-28 compared to glibenclamide alone treated groups with similar dosing regimen. Glibenclamide upon co-administration with MC extract showed improved pharmacodynamic parameters compared to glibenclamide alone treated groups suggesting synergistic or additive effect. Physician can reduce the glibenclamide dose in diabetic patients if they are taking MC as supplement.

Antenatal steroids elicited neurodegenerative-associated transcriptional changes in the hippocampus of preterm fetal sheep independent of lung maturation

BackgroundAntenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks’ gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function.MethodsDate-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122–125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection.ResultsPreterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration (“Prion Disease”, “Alzheimer’s Disease”, “Arachidonic Acid metabolism”). Adverse changes were independent of respiratory function during ventilation.ConclusionsOur data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens.

Effectiveness of Zinc Supplementation for Sepsis Treatment: A Single-Center Retrospective Observational Study.

Zinc plays an important role in sepsis; however, the effectiveness of zinc supplementation and the appropriate dose remain unclear. This study aimed to verify the effectiveness of zinc supplementation and the appropriate dose in patients with sepsis. This single-center retrospective observational study included 247 patients with sepsis from 1 April 2015 to 31 March 2023 who were receiving ventilatory management. The patients were divided into three groups according to the zinc supplementation dose: <15 mg, 15-50 mg, and ≥50 mg. The <15 mg, 15-50 mg, and ≥50 mg groups had 28 (19%), six (21%), and 16 deaths (22%) at discharge, with no statistically significant difference (p = 0.36). No statistically significant differences were observed in the length of intensive care unit (ICU) stay (p = 0.06). A higher supplementation dose corresponded with a statistically significant increase in blood zinc concentration in the first week (38.5 ± 16.6 µg/dL, 58.8 ± 19.7 µg/dL, 74.2 ± 22.5 µg/dL, respectively; p < 0.01) but not in the second or third weeks (p = 0.08, 0.19, respectively). Zinc supplementation did not reduce the mortality rate or length of ICU stay or contribute to an increased serum zinc concentration. High-dose zinc supplementation may not be effective during acute sepsis.

Brain Stem Glioma Recurrence: Exploring the Therapeutic Frontiers.

Gliomas of the brainstem represent a small percentage of central nervous system gliomas in adults. Due to the proximity of the tumor to critical structures, radical surgery is highly challenging and limited to selected cases. In addition, postoperative treatments, which become exclusive to non-operable patients, do not guarantee satisfactory disease control, making the progression of the disease inevitable. Currently, there is a lack of therapeutic options to control tumor growth after the diagnosis of recurrence. The rarity of these tumors, their distinct behavioral characteristics, and the limited availability of tumor tissue necessary for the development of prognostic and predictive biomarkers contribute to the absence of a standardized approach for treating recurrent brainstem gliomas. A salvage radiotherapy (RT) retreatment could represent a promising approach for recurrent brainstem gliomas. However, to date, it has been mainly evaluated in pediatric cases, with few experiences available to assess the most appropriate RT dose, safety, and clinical responses in adult patients. This comprehensive review aims to identify instances of adult patients with recurrent brainstem gliomas subjected to a secondary course of RT, with a specific focus on the analysis of treatment-related toxicity and outcomes. Through this investigation, we endeavor to contribute valuable insights into the viability and efficacy of salvage RT retreatment in managing recurrent brainstem gliomas in the adult population.

The use of reduced DOAC doses in atrial fibrillation patients does not always lead to good anticoagulation levels and avoid adverse events

BackgroundThe MAS study (Blood Advances 2024) showed that a high proportion of Italian AF patients treated with direct oral anticoagulants (DOACs) receive reduced doses. This sub-analysis of MAS data aimed to analyze the effects of reduced (appropriate or not)- or standard-dose use on DOAC activity assessed at baseline and the occurrence of thrombotic or bleeding complications during follow-up. MethodsThe MAS study design, the methods for DOAC measurement, the results, and the adverse events during follow-up, are described in detail elsewhere. ResultsSeven hundred AF patients (42 % of the total 1657) received a reduced dose (considered inappropriate in 140 [20 %]). They were older, more frequently women, with lower body mass index (BMI), hemoglobin levels, and creatinine clearance. They more often had cerebral or cardiovascular diseases, were taking more medications, with higher scores for thrombotic or bleeding risk. Despite the use of low doses, 133 (19.0 %) patients had high standardized C-trough DOAC levels and experienced a high proportion of bleeding events (8.3 % per year). Conversely, some patients (4.7 %) had very low levels, resulting in a high incidence of thrombotic events (6.7 % per year). No difference was detected if the reduced dose was appropriate or not. ConclusionThe unpredictable, highly variable inter-individual anticoagulant effect of DOACs may lead to either too low or too high anticoagulant levels, increasing the risk of thrombotic or bleeding events. This is particularly relevant for patients with high-risk conditions, such as those chosen for reduced-dose treatment. Further studies are needed to investigate this important clinical issue.

Practical guidance on the assessment of radiation risks for diagnostic radiological examinations.

Patient doses cannot be limited; instead, radiological examinations should be justified and optimized to ensure the necessary diagnostic or therapeutic effect with the lowest patient dose achievable. Assessment of the radiation risks from patient exposure is important part of the justification process. Hence, medical staff within the framework of their professional activities should possess necessary information on the data on radiation risk from different types of radiological procedures. An approach has been developed that allows considering age and gender dependences of the risk coefficients of radiogenic cancer and the age and gender distribution of patients for various radiological examinations to assess the individual radiation risk for patient and collective risk for population from medical exposure. The approach is based on a new expanded use of the effective dose concept proposed in ICRP Publication 147 and demonstrated using the medical exposure in the Russian Federation as the example. For 30 radiological examinations that compose about 80% of the collective dose from medical exposure of the public in the Russian Federation radiation risk was assessed based on calculated age and gender specific risk coefficients per unit effective dose. For the rest of the examinations a simplified approach was used to assess the risk, which was based on using an age and gender specific risk coefficient determined for one of 4 anatomical regions (head, neck, chest and abdomen) or for uniform irradiation of the whole body. The proposed approach allows significantly improving the assessment of the radiation risk while continuing to use the effective dose as a dosimetric quantity within the framework of the state program in the Russian Federation. As a result the collective risk from medical examinations in the Russian Federation in 2022 was lower by the factor of 3 compared to the previous assessment based on the effective dose with the nominal risk coefficient.

Results of the JRS-I LRA0401 and LRB0402 Japan Rhabdomyosarcoma Study Group trials for low-risk embryonal rhabdomyosarcoma.

Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4g/m2. However, this dose may increase the risk of adverse events, including infertility, in some patients. The JRS-I LRA0401 and LRB0402 protocols aimed to reduce the cyclophosphamide dose to 9.6g/m2 and 17.6g/m2, respectively, without decreasing the FFS rates. Subgroup-A patients received eight cycles (24weeks) of vincristine, actinomycin D, and 1.2g/m2/cycle cyclophosphamide. Subgroup-B patients received eight cycles (24weeks) of vincristine, actinomycin D, and 2.2g/m2/cycle cyclophosphamide, followed by six cycles (24weeks) of vincristine and actinomycin D. Group II/III patients in both subgroups received radiotherapy. In subgroup A (n = 12), the 3-year FFS rate was 83% (95% confidence interval [CI], 48-96), and the 3-year overall survival (OS) rate was 100%. Only one isolated local recurrence was observed (8.3%). There were no unexpected grade-4 toxicities and no deaths. In subgroup B (n = 16), the 3-year FFS and OS rates were 88% (95% CI, 59-97) and 94% (95% CI, 63-99), respectively. There were no unexpected grade 4 toxicities and no deaths. Shorter duration therapy using vincristine, actinomycin D, and lower dose cyclophosphamide with or without radiotherapy for patients with low-risk subgroup A rhabdomyosarcoma (JRS-I LRA0401 protocol) and moderate reduction of cyclophosphamide dose for patients with low-risk subgroup B rhabdomyosarcoma (JRS-I LRB0402 protocol) did not compromise FFS.

A Whole-Spine Radiography Study to Reduce Patient Exposure Dose and Artifacts Using the EOS Imaging System.

Whole-spine radiography can be accomplished through two methods: (1) segmented imaging employing X-ray tube angulation and detectors, or (2) the Euronext Paris Advanced Orthopedic Solutions (EOS) 2D Imaging system that can capture the entire spine in a single image using X-ray tubes and detectors oriented at a 90-degree angle. This study aimed to establish optimal EOS examination parameters based on patient morphotype and scan speed to reduce patient radiation exposure, repeat examinations, heat stress on equipment, and X-ray tube cooling time. X-ray exposure conditions involved adjustments of scan speed ranging from two to four steps, contingent upon the patient's morphotype ('S', small body; 'M', medium body; and 'L', large body. Patient dose measurements were conducted 20 times for each set of conditions. When transitioning from an 'S' to an 'M' morphotype at a constant scan speed, the entrance skin dose (ESD) exhibited an increase of approximately 41.25 ± 4.57%. A similar change from an 'M' to an 'L' morphotype resulted in an ESD increase of roughly 59.56 ± 24.00%. A transition from an 'S' to an 'L' morphotype at the same scan speed manifested an ESD elevation of approximately 124.21 ± 26.96%. This study underscores significant variations in radiation dose, ranging from 40% to 50%, when altering morphotype while maintaining a consistent scan speed.

Meta-analysis of genome-wide association studies of stable warfarin dose in patients of African ancestry

AbstractWarfarin dose requirements are highly variable because of clinical and genetic factors. Although genetic variants influencing warfarin dose have been identified in European and East Asian populations, more work is needed to identify African-specific genetic variants to help optimize warfarin dosing. We performed genome-wide association studies (GWASs) in 4 African cohorts from Uganda, South Africa, and Zimbabwe, totaling 989 warfarin-treated participants who reached stable dose and had international normalized ratios within therapeutic ranges. We also included 2 African American cohorts recruited by the International Warfarin Pharmacogenetics Consortium (n = 316) and the University of Alabama at Birmingham (n = 199). After the GWAS, we performed standard error-weighted meta-analyses and then conducted stepwise conditional analyses to account for known loci in chromosomes 10 and 16. The genome-wide significance threshold was set at P < 5 × 10−8. The meta-analysis, comprising 1504 participants, identified 242 significant SNPs across 3 genomic loci, with 99.6% of these located within known loci on chromosomes 10 (top SNP: rs58800757, P = 4.27 × 10−13) and 16 (top SNP: rs9925964, P = 9.97 × 10−16). Adjustment for the VKORC1 SNP -1639G>A revealed an additional locus on chromosome 2 (top SNPs rs116057875/rs115254730/rs115240773, P = 3.64 × 10−8), implicating the MALL gene, that could indirectly influence warfarin response through interactions with caveolin-1. In conclusion, we reaffirmed the importance of CYP2C9 and VKORC1 in influencing warfarin dose requirements, and identified a new locus (MALL), that still requires direct evidence of biological plausibility.

Different diabetogenic effect of statins according to intensity and dose in patients with acute myocardial infarction: a nationwide cohort study

Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan–Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024–1.692; P < 0.032). Higher dose of rosuvastatin was associated with a higher cumulative incidence of NODM, but this dose-dependency was not apparent with atorvastatin. Cumulative incidence of MACE decreased dose-dependently only with atorvastatin. High-intensity statin was associated with a higher cumulative incidence of NODM in AMI patients, and this association was more evident in rosuvastatin. The different diabetogenic effects of the two statins provide supporting evidence for understanding the nuanced nature of statin treatment in relation to NODM.

Opicapone for the treatment of early wearing-off in levodopa-treated Parkinson’s disease: pooled analysis of patient level data from two randomized open-label studies

BackgroundThe wearing-off phenomenon is a key driver of medication change for patients with Parkinson’s disease (PD) treated with levodopa. Common first-line options include increasing the levodopa dose or adding a catechol-O-methyltransferase (COMT) inhibitor, but there are no trials comparing the efficacy of these approaches. We evaluated the effectiveness of adjunct opicapone versus an additional 100 mg levodopa dose in PD patients with early wearing-off using pooled data from 2 randomized studies.MethodsThe ADOPTION study program included two similarly designed 4-week, open-label studies conducted in South Korea (NCT04821687) and Europe (NCT04990284). Patients with PD, treated with 3–4 daily doses of levodopa therapy and with signs of early wearing-off were randomized (1:1) to adjunct opicapone 50 mg or an additional dose of levodopa 100 mg. Patient-level data from the two studies were pooled.ResultsThe adjusted mean [SE] change from baseline to week 4 in absolute OFF time (key endpoint) was − 62.8 min [8.8] in the opicapone group and − 33.8 min [9.0] in the levodopa 100 mg group, the difference significantly favoring opicapone (− 29.0 [− 53.8, − 4.2] min, p = 0.02). Significant differences in the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale Part III subscore (− 4.1 with opicapone vs − 2.5 with levodopa 100 mg), also favored opicapone (− 1.7 [− 3.3, − 0.04], p < 0.05). Dyskinesia was the most frequently reported adverse event (opicapone 7.2% vs. levodopa 100 mg 4.2%).ConclusionsIn these short-term trials, introducing adjunct opicapone was more effective at reducing OFF time than adding another 100 mg levodopa dose in PD patients with early signs of wearing-off.

One-year outcome of robotical vs. manual percutaneous coronary intervention.

Robotic-assisted percutaneous coronary intervention (R-PCI) is a promising technology for optimizing the treatment of patients with coronary heart disease. For a better understanding of the potential of R-PCI in clinical routine compared to conventional manual PCI (M-PCI) both initial treatment success of the index procedure and long-term outcome have to be analysed. Prospective evaluation from the FRiK (DRKS00023868) registry of all R-PCI cases with the CorPath GRX Cardiology by Siemens Healthineers and Corindus in the Freiburg University Heart Center between 04/2022 and 03/2023. Index procedure success and safety, radiation dose of patients and personnel, and 1-year outcome will be reported. Findings will be compared to a prospective control group of M-PCI patients treated by the same team of interventionalists during the same observation period. Seventy patients received R-PCI and were included in the registry. PCI success rate was 100%, with 19% requiring manual assistance. No complications (MACE-major adverse cardiovascular events) occurred. Compared with 70 matched-pair M-PCI patients, there was a higher median procedural time (103min vs. 67min, p < 0.001) and fluoroscopy time (18min vs. 15min, p = 0.002), and more contrast volume was used (180 ml vs. 160ml, p = 0.041) in R-PCI vs. M-PCI patients. However, there was no significant difference of the dose-area product (4062 vs. 3242 cGycm2, p = 0.361). One year after the intervention, there was no difference in mortality, rehospitalisation, unscheduled PCI or target vessel failure. Health-related quality of life evaluation 6 and 12months after the index procedure (NYHA, CCS, SAQ7 and EQ-5D-5L) was similar in both groups. R-PCI is feasible and safe. Compared to M-PCI, index procedure success rate is high, safety profile is favourable, and manual assistance was required in only few cases. At 1-year follow-up results for R-PCI vs. M-PCI considering mortality, rehospitalisation, morbidity and target vessel failure were equal.

Evaluation of the Predictive Character of the Expiratory Inferior Vena Cava/Abdominal Aorta (eIVC/Ao) Index for Minimum Blood Pressure Following Spinal Anesthesia With 0.5% Hyperbaric Bupivacaine.

Spinal anesthesia has many side effects, one of them being a drop in blood pressure (BP). Identifying predictive factors for this drop is a clear matter of concern. In this regard, the expiratory inferior vena cava/abdominal aorta (eIVC/Ao) index has already been spotted as such for doses of 0.5% hyperbaric bupivacaine greater than 12mg. Departing from the demonstrated correlation between this index and hypotension post-spinal anesthesia, our study aimed to (1) evaluate whether an eIVC/Ao index greater than 0.7, thus defining non-hypovolemic patients, can also predict minimal BP for doses inferior to 12mgand (2) identify other predictive factors for minimal BP post-spinal anesthesia. Lastly, we verified whether preoperative fasting induces hypovolemia. This single-center prospective observational pilot study included 20 patients. The baseline measurements of BP, eIVC/Ao index, and fasting time were recorded at time T0'. Then spinal anesthesia was administered with 0.5% hyperbaric bupivacaine in doses inferior to 12 mg. The patients' systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and metameric levels were each recorded at times T5', T10', T15', and T20'. The results indicated that baseline DBP was predictive of low DBP and minimum MAP, which reflect myocardial perfusion and systemic pressures, respectively. Therefore, it should trigger prophylaxis (spinal-lateralized, continuous, or lower dose) in patients with a low DBP baseline. Additionally, baseline SBP was predictive of minimumSBP, an independent risk factor for post-anesthetic hypotension if its baseline is lessthan 120 mmHg. Although female gender was linked to minimum SBP, other confounding factors (size, dose administered, and type of surgery related to gender) must also be considered. Moreover, a correlation was established between height and MAP in parturients. Hypotension was not recorded at local anesthetic (LA) doses between 8 and 12 mg and the doses administered were sufficient to achieve the metameric levels required for surgery (ether tests). Since 8 mg of 0.5% hyperbaric bupivacaine achieved the same level as 12 mg, lower doses of LA might prevent a significant drop in BP and its deleterious effects. Therefore, in the current cohort, the eIVC/Ao index was not predictive of minimum BP during spinal anesthesia with doses less than 12 mg of 0.5% hyperbaric bupivacaine. However, predictive factors for minimum BP included gender and baseline SBP (for minimum SBP), height and baseline DBP (for minimum MAP), and baseline DBP (for minimum DBP). Lastly, preoperative fasting did not cause hypovolemia.

A growth-differentiation factor 15 receptor agonist in randomized placebo-controlled trials in healthy or obese persons.

Growth Differentiation Factor 15 (GDF15), a divergent member of the TGF-β superfamily, signals via the hindbrain glial-derived neurotrophic factor receptor alpha-like and rearranged during transfection receptor co-receptor (GFRAL-RET) complex. In nonclinical species, GDF15 is a potent anorexigen leading to substantial weight loss. MBL949 is a half-life extended recombinant human GDF15 dimer. MBL949 was evaluated in multiple nonclinical species and then in humans in two randomized and placebo-controlled clinical trials. In the Phase 1 first-in-human, single ascending dose trial MBL949 or placebo was injected subcutaneously to overweight and obese healthy volunteers (n=65) at doses ranging from 0.03 to 20 mg. In Phase 2, MBL949 or placebo was administered subcutaneously every other week for a total of 8 doses to obese participants (n=126) in five different dose regimens predicted to be efficacious based on data from the Phase 1 trial. In nonclinical species, MBL949 was generally safe and effective with reduced food intake and body weight in mice, rats, dogs, and monkeys. Weight loss was primarily from reduced fat, and metabolic endpoints improved. A single ascending dose study in overweight or obese healthy adults demonstrated mean terminal half-life of 18-22 days, and evidence of weight loss at the higher doses. In the Phase 2, weight loss was minimal following biweekly dosing of MBL949 for 14 weeks. MBL949 was safe and generally tolerated in humans over the dose range tested, adverse events of the gastrointestinal system were the most frequent observed. The prolonged half-life of MBL949 supports biweekly dosing in patients. MBL949 had an acceptable safety profile. The robust weight loss observed in nonclinical species did not translate to weight loss efficacy in humans. ClinicalTrials.gov NCT05199090.