Increase In Dose Research Articles

Research on the Stability and Response of Food Packaging Polystyrene Resin Materials to γ-ray Irradiation.

Radiation stability of food packaging materials is the key to ensuring food quality. In this study, 60Co γ-ray was selected to investigate the radiation resistance of food packaging polystyrene (PS) resin material, although the FTIR analysis showed that the intensity of several peaks decreased slightly. The gel permeation chromatography (GPC) results displayed that the value of peak molecular weight (Mp) of PS went from 2.68 × 105 g/mol down to 2.22 × 105 g/mol. Moreover, the residual mass (Res) of PS increased from 7.208 to 30.23%, indicating that the tendency of coking of PS was stronger after irradiation. In addition, the peak intensities of the three main pyrolysis products -CH2-, CH4, and CH2=CH2 increased by more than 30% compared to unirradiated PS, and a large number of them were detected in the whole pyrolysis process. Moreover, mechanical property analysis finds that both breaking strength and elongation data increased before irradiation dose of 50 kGy, then, decreased sharply with further increase of irradiation dose. The theoretical bond order analysis confirmed that the tertiary carbon bond attaching the benzene ring had the lowest bond energy. This study can give helpful guidance when using PS for food packing materials.

On the response of the CR-39 NTD to low doses of gamma rays using optical and photoluminescence spectroscopy

In this work, the response of the CR-39 nuclear track detector (NTD) exposed to different low doses of gamma rays was investigated using UV–Vis and photoluminescence spectroscopy. Five NTDs of CR-39 were irradiated with low gamma-ray doses ranging from 10 to 120 kGy using a60Co source. The dose of gamma rays correlates with red shift in the absorption spectra of a gamma-irradiated CR-39 detector. As the gamma dose increases, the indirect and direct energy band gaps, as well as Urbach energy, decrease gradually. However, the decrease in the indirect optical band gap is greater than the decrease in the direct band gap. The observed spectra of the CR-39 detector after being irradiated with different doses of γ-rays showed an acceptable variation in photoluminescence (PL) emission spectra generated by a well-defined excitation wavelength of 290 nm. Starting at 45 kGy dose, the integrated area of the photoluminescence peak increases and tends to saturate, whereas the photoluminescence peak height is linearly correlated with the gamma dose with high sensitivity, which is 53.1 ± 6.3 CPS. kGy−1. According to the current findings, photoluminescence (PL) spectroscopy has a greater sensitivity than UV–Vis spectroscopy for measuring the response of the CR-39 detector to gamma rays in the dose range of 10–120 kGy. The results reflected a potential possibility of using the CR-39 detector in dosimetric applications of low gamma ray doses through the high resolution achieved by photoluminescence (PL) and UV–Vis spectroscopy.

Abstract P327: Comparing the Blood Pressure Response to Antihypertensive Treatment Intensification and Dose Increase to No Action for Uncontrolled Hypertension

Background: The addition of a new antihypertension medication class (CA) or dose increase (DI) in patients with hypertension (HTN) is relatively infrequent when HTN is uncontrolled (blood pressure [BP, mmHg] ≥ 140/90) during outpatient visits. We compared systolic (S)BP changes following CA, DI, or no medication changes for uncontrolled BP. Methods: A patient cohort from 6 diverse healthcare organizations, engaged in a quality improvement program, was identified with previously diagnosed HTN. Uncontrolled outpatient SBP measurements observed at participating program sites were compared to follow-up measurements within 7 to 120 days for evaluating SBP change. ANCOVA and linear regression analyses were used to control clinical and demographic covariates and assess differences in SBP change following treatment decision. Results: A prospective cohort of 124,068 patients with HTN spanning 280,937 events was identified, mean age 63.3 ± 13.9. Class addition reduced SBP 2.0 mmHg (95% CI, 1.81 – 2.24), whereas dose increase did not lower SBP [-0.07 (95% CI, -0.31, 0.16)]. Conclusion: In this study, CA lowered BP modestly, whereas DI appeared ineffective. Since patients were not randomized, our results may under-estimate the effects of CA and DI on BP, i.e., clinicians may have expected a greater decline of SBP than simply regression to the mean for patients with uncontrolled hypertension in the absence of DI or TI. Our data are consistent with reports that CA has a greater effect to lower BP than DI. Our findings also highlight some challenges of interpreting real world data compared to randomized clinical trials.

Pathophysiologic Vasodilation in Cardiogenic Shock and Its Impact on Mortality.

Cardiogenic shock (CS) mortality remains near 40%. In addition to inadequate cardiac output, patients with severe CS may exhibit vasodilation. We aimed to examine the prevalence and consequences of vasodilation in CS. We analyzed all patients hospitalized at a CS referral center who were diagnosed with CS stages B to E and did not have concurrent sepsis or recent cardiac surgery. Vasodilation was defined by lower systemic vascular resistance (SVR), higher norepinephrine equivalent dose, or a blunted SVR response to pressors. Threshold SVR values were determined by their relation to 14-day mortality in spline models. The primary outcome was death within 14 days of CS onset in multivariable-adjusted Cox models. This study included 713 patients with a mean age of 60 years and 27% females; 14-day mortality was 28%, and 38% were vasodilated. The median SVR was 1308 dynes•s•cm-5 (interquartile range, 870-1652), median norepinephrine equivalent was 0.11 µg/kg per minute (interquartile range, 0-0.2), and 28% had a blunted pressor response. Each 100-dynes•s•cm-5 decrease in SVR below 800 was associated with 20% higher mortality (adjusted hazard ratio, 1.23; P=0.004). Each 0.1-µg/kg per minute increase in norepinephrine equivalent dose was associated with 15% higher mortality (adjusted hazard ratio, 1.12; P<0.001). A blunted pressor response was associated with a nearly 2-fold mortality increase (adjusted hazard ratio, 1.74; P=0.003). Pathophysiologic vasodilation is prevalent in CS and independently associated with an increased risk of death. CS vasodilation can be identified by SVR <800 dynes•s•cm-5, high doses of pressors, or a blunted SVR response to pressors. Additional studies exploring mechanisms and treatments for CS vasodilation are needed.

A lung SBRT treatment planning technique to focus high dose on gross disease

This study investigated a straightforward treatment planning technique for definitive stereotactic body radiation therapy (SBRT) for patients with early-stage lung cancer aimed at increasing dose to gross disease by strategically penalizing the normal tissue objective (NTO) in the EclipseTM treatment planning system. Twenty-five SBRT cases were replanned to 50 Gy in 5 fractions using static and dynamic NTO methods (50 plans total). The NTO had a start dose of 100% at the target border, end dose of 20%, fall-off rate of 0.4/mm, and a priority of 150. For the static NTO plans, a lower planning target volume (PTV) objective was placed at 52 Gy with a priority of 100. Maximum dose was not penalized. Optimization was performed without user interaction. In contrast, the planner incrementally increased the priority of the NTO on the dynamic NTO plans until 95% of the target volume was covered by the prescription dose. Further, the dynamic NTO plans used both PTV lower and upper objectives at 63-64 Gy with priorities of 50. Maximum dose was penalized to ensure that the hot spot was within ± 2% of the static NTO global maximum dose. Following optimization, all plans were normalized so that the prescription dose covered 95% of the PTV. Plans were scored based on RTOG 0813 criteria, and dose to the internal target volume (ITV) and PTV was evaluated. The Wilcoxon signed-rank test (threshold = 0.05) was used to evaluate differences between the static and dynamic NTO plans. All plans met RTOG 0813 planning guidelines. In comparison to the static NTO plans, the dynamic NTO plans exhibited statistically significant increases in PTV mean dose, ITV mean dose, and PTV-ITV mean dose. Notably, the dynamic NTO plans more effectively concentrated the high dose on gross disease at the center of the PTV. As compared to the static NTO plans, the mean dose was 4.6 Gy higher in the ITV while only 1.3 Gy higher in the PTV-ITV rind of the dynamic NTO plans. Global maximum doses were similar. There were some small yet statistically significant differences in dose conformity between plan types. Furthermore, the dynamic NTO plans demonstrated a significant reduction in total monitor units (MU). This study demonstrated an efficient optimization strategy for lung SBRT plans that concentrates the highest dose in the gross disease, which may improve local control.

Abstract P117: Provider Concordance to the Current 2017 High Blood Pressure (BP) Clinical Practice Guidelines and Patient Blood Pressure Control

Introduction: The AHA/ACC 2017 High BP guidelines introduced key changes, compared to previous guidelines, including a new hypertension definition (≥130/80 mm Hg) and lower medication thresholds for patients at cardiovascular risk. The impact of provider adherence to these guidelines on patient BP control has not been fully explored. Methods: We identified 3,749 new stage 1 hypertension patients (7,214 visits) and 11,013 new stage 2 hypertension patients (33,321 visits), aged ≥18, from the Vanderbilt University Medical Center database. We scrutinized outpatient BP levels, prescribed medications, follow-up visits, lab results, demographics, comorbid conditions, and physician notes from January 2018 to December 2022. This data was compared to hypertension treatment criteria developed from the 2017 guidelines that was validated by six hypertension experts. Active primary care patients (with 1 visit per year) were included. Mixed-effects Poisson regression and mixed-effects linear regression examined the relationship between guideline adherence and controlled BP (&lt;130/80 mm Hg) and continuous BP, respectively. Results: Among stage 1 hypertension visits, 12.2% were treated with at least one antihypertensive drug according to guidelines, resulting in a 13% increase in BP control and a reduction in systolic BP by 2.02 mm Hg. For stage 2 hypertension visits, 26% received treatment with at least two first-line antihypertensive drug classes, leading to a 45% increase in BP control and reductions in systolic and diastolic BP by 3.79 mm Hg and 1.93 mm Hg, respectively. No significant difference in BP control was observed among stage 2 patients treated with two versus one first-line drug. Adherence to follow-up guidelines resulted in a 24% improvement in BP control for stage 1 patients and stage 2 patients when their follow-up visit occurred within 1 month. Subsequent follow-up visits within 1-month improved BP control by 34% if BP was not controlled previously. Additionally, 42.4% of patients with uncontrolled BP for 1 month received an increase in medication dose or a change/addition of medication class and showed a 7% increase in BP control within next month. Conclusion: Provider adherence to recommended antihypertensive drug treatment guidelines (12%-26%), follow-up assessments guidelines (29%-37%), and treatment intensification (42.4%) were poor. However, patients treated according to the guidelines showed significant improved BP control.

Agranulocytosis Induced by Overdosage of Mercaptopurine: A Case Report

Drug-induced agranulocytosis (DIAG) is a rare but potentially fatal hematological complication. Thiopurines, such as mercaptopurine (6-MP), are widely used in the treatment of chronic inflammatory bowel diseases (IBD), but can cause myelotoxicity due to the accumulation of active metabolites. We report the case of a 48-year-old woman with ulcerative colitis who developed severe agranulocytosis following an accidental overdose of 6-MP. The patient presented with febrile pancytopenia with a neutrophil count of 0.04 G/L. Bone marrow examination revealed normal cellularity with an inversion of the maturation pyramid of the granulocyte lineage. A treatment combining growth factors (filgrastim) and antibiotics (tazobactam) was initiated, leading to progressive improvement over 5 weeks. The toxicity of 6-MP is mainly due to the accumulation of 6-thioguanine nucleotides (6-TGN). The polymorphism of the gene encoding the enzyme thiopurine S-methyltransferase (TPMT) can influence the risk of myelotoxicity. Two strategies are proposed to minimize this risk: evaluation of TPMT activity with dosage adjustment, or regular monitoring of blood counts with gradual dose increase. This case highlights the importance of rigorous biological monitoring when initiating 6-MP treatment, regardless of the TPMT test. Increased vigilance is necessary when using immunosuppressive drugs in the treatment of IBD to optimize efficacy and minimize toxicity.

Hemodynamic Collapse After Intubation in Critical Care Transport

Objectives The aim of this study was to describe the incidence of and modifiable risk factors for post intubation hemodynamic collapse in prehospital and interfacility critical care transport. Methods Single center retrospective chart review of adult patients (≥18 years) intubated by a critical care transport team between January 2017 and May 2023. The primary outcome was incidence of hemodynamic collapse (systolic blood pressure <90 mmHg for greater than 30 min, new vasopressor requirement, vasopressor dose increase, fluid bolus of >15 mL/kg, systolic blood pressure <65 mmHg at least once, or cardiac arrest). Secondary outcomes included post intubation hypoxia, as well as association of hemodynamic collapse with potentially modifiable risk factors including pre intubation shock index, pre intubation heart rate, pre intubation systolic blood pressure, and induction agent. Results Three hundred and thirty-three patients were included. Ninety-seven (29.1%) patients experienced hemodynamic collapse and 36 (10.8%) of patients experienced life threatening hemodynamic collapse. Pre intubation shock index >1 (OR 3.18, 95% CI 1.15–8.74) was associated with post intubation hemodynamic collapse. Choice of induction agent, fluid bolus prior to intubation, location of intubation, presence of traumatic injury, and age were not correlated with risk of hemodynamic collapse. The number of intubation attempts and methods of intubation were similar between groups. Conclusions Hemodynamic collapse and life-threatening hemodynamic collapse after intubation occurred frequently in this critical care transport cohort. Shock index greater than one was associated with significantly higher risk of hemodynamic collapse and life-threatening hemodynamic collapse.

Adsorption Studies of Pb&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt;, Cu&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt; and Cr&amp;lt;sup&amp;gt;3+&amp;lt;/sup&amp;gt; from Aqueous Solution Using &amp;lt;i&amp;gt;Azadirachta Indica &amp;lt;/i&amp;gt;(Neem) Seed Husk and &amp;lt;i&amp;gt;Adansonia Digitata &amp;lt;/i&amp;gt;(Baobab) Seeds

The adsorption of Pb&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt;, Cu&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt; and Cr&amp;lt;sup&amp;gt;3+&amp;lt;/sup&amp;gt; from aqueous solution using Neem seed husk (NSH) and baobab seed (BS) were studied through the use of batch adsorption system. The adsorbents were prepared by drying at 120°C for 24hours and were characterized using FT-IR, XRD, and SEM analysis. The FTIR spectroscopy revealed the presence of O-H, N-H, C-H, C=C, C=O, and C-O stretching; XRD revealed the particle sizes as 44.51nm for NSH and 42.61nm while the morphology of the NSH and BS were revealed by SEM to be porous for NSH and BS. Various parameters such as, initial metal ion concentration, adsorbent dosage, contact time, Temperature and pH of metal ion solution were investigated in a batch-adsorption System. The adsorption uptake was found to increase with increase in adsorbent dose, contact time and temperature but decreases with the initial concentration. The uptake of the metal ions increases and reaches optimum at pH of 4-6. The maximum adsorption capacity was found to be Pb-NSH (15.267mg/g) and Cu-NSH (19.46mg/g). Adsorption of Cu&amp;lt;sup&amp;gt;2+&amp;lt;/sup&amp;gt;onto NSH fitted Langmuir isotherm model with (R&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt; &amp;gt; 0.93) while Adsorption of Pb-NSH Fitted Freundlich isotherm Model with (R&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt;&amp;gt; 0.99). Kinetic data fitted pseudo-second-order model (R&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt; &amp;gt; 0.98) which was more suitable in explaining the adsorption rate. Thermodynamic data showed that Gibb’s free energy (ΔG°) values for all metal ions were negative indicating feasibility and favorability of adsorption. Positive enthalpy change (ΔH°) and Entropy change (ΔS°) values indicate endothermic processes and increase in randomness.

Analyzing the Impact of Annealed Steel Sludge Doses on the Physicochemical Properties of Biochar Obtained from Waste Date Palm Frond

Large quantities of date palm frond waste generated from the pruning process are accumulated or burned in burn barrels, harming the environment and having very little economic value. However, because of the lack of data revealing the characteristic magnetic properties of biochar derived from date palm fronds, further research on low-cost and sustainable strategies could offer a new composite material and serve to extend the way for novel applications. In this study, we prepared biochar derived from palm fronds via pyrolysis under a limited-oxygen atmosphere at a lower temperature of 300 °C for 2 h. We introduced a facile strategy for the production of magnetic biochar with various doses of annealed steel sludge material via ball milling. Various amounts of annealed steel sludge material (5%, 15%, and 25% w) were added to date palm frond biochar, and the obtained product was fabricated by ball milling. The physicochemical characteristics of the magnetic biochar composite were subsequently analyzed using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) spectroscopy, and UV-vis spectroscopy. Our findings showed that the ball milling method is a successful step for producing date palm fronds with magnetic biochar material possessing rough and packed pores, as shown by SEM. XRD patterns assumed the existence of magnetic phases of iron oxide (magnetite (Fe3O4), hematite (α-Fe2O3), and maghemite (γ-Fe2O3) at different generated peaks. FTIR outputs exhibited the abundant presence of various oxygen-containing functional groups (- COOH and -OH) on the surface of magnetic biochar material, which help to create chemically reactive sites to adsorb potential surrounding species. The UV spectra showed a noticeable enhancement of the optical properties of the magnetic biochar with an increase in the sludge dose for light absorption in the visible region from wavelengths of 400 – 700 nm . This result signifies the synthetic optimization and potential application of magnetic biochar materials for composites that could be employed in targeted uses including soil amendment, water remediation and energy applications.

Efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for Helicobacter pylori infection: Real-world evidence.

Tegoprazan, a novel potassium-competitive acid blocker, has been approved for Helicobacter pylori eradication in Korea. We compared the efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for H.pylori eradication in real-world clinical practice. We retrospectively analyzed data from patients with H.pylori infection treated with tegoprazan- or rabeprazole-based concomitant therapies. The primary endpoint was H.pylori eradication rate. The secondary endpoint was adverse events. Among the 1474 included patients, 620 and 854 received tegoprazan- and rabeprazole-based concomitant therapies, respectively. Intention-to-treat analysis showed no significant difference in the eradication rates between the tegoprazan- and rabeprazole-based concomitant therapy groups (74.7% [95% confidence interval [CI], 71.1-78.0%] vs 72.7% [95% CI, 69.7-75.6%], P=0.400). Per-protocol analysis also demonstrated similar eradication rates for the groups (tegoprazan vs rabeprazole: 88.0% [95% CI, 85.0-90.6%] vs 85.9% [95% CI, 83.2-88.3%], P=0.288). Although the overall adverse event rate did not differ between groups (tegoprazan vs rabeprazole, 39.2% vs 40.6%, P=0.578), abdominal discomfort was less frequent in the tegoprazan group than in the rabeprazole group (1.3 vs 4.8%, P=0.001). Tegoprazan- and rabeprazole-based concomitant therapies for H.pylori eradication showed comparable efficacy and overall safety. The effect of tegoprazan on dose increases or other regimens, such as bismuth-containing quadruple therapy, should be further evaluated, because the efficacy of tegoprazan-based concomitant therapy may be suboptimal in regions where the clarithromycin resistance rate is high.

Recommended doses of endovenous vancomycin are insufficient to achieve therapeutic concentrations in paediatric patients

ObjectivesVancomycin therapeutic drug monitoring is challenging, especially in the paediatric population where evidence is scarce. The main objective of this study was to analyse the achievement of therapeutic concentrations of...

Treatment Targets Should Influence Choice of Infliximab Dose Intensification Strategy in Inflammatory Bowel Disease: A Pharmacokinetic Simulation Study.

The optimal infliximabdose intensification strategy to address loss of response associated with subtherapeutic infliximabtrough levels remains uncertain, as does whether post-intensification trough and treatment targets should influence this decision. This pharmacokineticsimulation study aimed to identify infliximab dose intensification strategies capable of achieving post-intensification infliximab trough thresholds associated with clinical and objective treatment targets in Crohn's disease and ulcerative colitis. A validated pharmacokinetic infliximab model, applied to 200 simulated patients, identified those with subtherapeutic (<3.00mg/L) trough levels after 30weeks of standard (5mg/kg 8-weekly) dosing, and subsequently applied 10 dose intensification strategies over a further 32weeks. The proportion of simulations achieving 32-week post-intensification infliximab trough levels associated with endoscopic remission (ulcerative colitis >7.50 mg/L, Crohn's disease >9.70 mg/L) was the primary outcome, with perianal fistula healing (Crohn's disease >10.10 mg/L) and clinical improvement (ulcerative colitis >3.70 mg/L, Crohn's disease >7.00mg/L) evaluated as secondary outcomes. All outcomes were stratified by intensity of dose intensification, with standard (≤10mg/kg 8-weekly or 5mg/kg 4-weekly; n=5) and intensive (>10mg/kg 8-weekly or 5mg/kg 4-weekly; n=5) dosing strategies defined, respectively. The median pre-intensification infliximab trough level was 0.91mg/L (interquartile range 1.37). Intensive dosing strategies were more likely to achieve infliximab trough concentrations associated with endoscopic remission (ulcerative colitis 36.48% vs. 10.80%, Crohn's disease 25.98 vs. 4.68%), perianal fistula healing (24.52% vs. 4.36%) and clinical improvement (ulcerative colitis 61.90% vs. 34.86%, Crohn's disease 40.32 vs. 12.08%) than standard intensification strategies (all p<0.01). When controlling for cumulative (mg/kg) infliximab dose over 32weeks, strategies that concurrently dose increased and interval shortened achieved the highestinfliximab trough levels (all p<0.01). This simulation-based analysis highlights the potential of using post-intensification infliximab trough thresholds associated with aspirational treatment targets in Crohn's disease and ulcerative colitis to guide choice of infliximab dose intensification strategy. Intensive dose intensification strategies, particularly those that concurrently dose increase and interval shorten, appear to achieve higher infliximab levels than standard dose intensification strategies. This may be particularly important in the pursuit of stringent endpoints, such as endoscopic remission and fistula healing, which have been consistently associated with higher infliximab trough levels. These findings require validation across real-world cohorts.

Assessment of the hormesis effect and toxic damage of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus)

The present study was conducted to evaluate the hormesis and toxicity of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus). Triplicate isonitrogenous and isocaloric aflatoxin B1 diets—CD (control, 0 ug/kg), D1 (20 ug/kg), and D2 (500 ug/kg)—were prepared and fed to grass carp with an initial mean body weight of (15.2 ± 0.1) g for 56 days. The results showed that the weight gain rate and specific growth rate of grass carp fed diet D2 were significantly higher, and the feed coefficient and crude fat content of the whole body were significantly lower (P &amp;lt; 0.05) compared with those fed diet CD. Serum superoxide dismutase content of grass carp fed D1 diet increased significantly (P &amp;lt; 0.05) with an increasing dose of aflatoxin B1, but when the dose reached 500 ug/kg (D2), serum superoxide dismutase, complement C3, and immunoglobulin M of grass carp decreased significantly (P &amp;lt; 0.05), while malondialdehyde increased significantly (P &amp;lt; 0.05). After short-term feeding of aflatoxin B1-containing diets (D1 and D2), liver body index, visceral body index, serum total cholesterol, triglyceride, and urea nitrogen content of grass carp increased significantly (P &amp;lt; 0.05), total bile acid secretion decreased significantly (P &amp;lt; 0.05), and structural damages such as increase in vacuoles, organizational structure loosening, and nucleus translocation were observed in the liver. Meanwhile, liver function indexes such as serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased significantly with the increase of aflatoxin B1 dose (P &amp;lt; 0.05). In addition, the height of intestinal villi, crypt depth, villus–crypt ratio, and tubular cell number, as well as the content of trypsin and lipase activities in the intestine of grass carp in the D2 group, were significantly higher than those in the CD group (P &amp;lt; 0.05). In conclusion, after a short-term intake of low doses of aflatoxin B1 (≤500 ug/kg), the toxicological damage of aflatoxin B1 was pronounced, although it produced a certain degree of hormesis on the growth performance and intestinal structure and function of grass carp. At a dose of 20 ug/kg, the non-specific immune system and liver structure and function of grass carp showed obvious toxic damage.

Hypogammaglobulinemia and Infection Events in Patients with Autoimmune Diseases Treated with Rituximab: 10 Years Real-Life Experience.

To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.

The effectiveness of 0.5 mg and 1mg of semaglutide in patients with type two diabetes and predictors of response: a retrospective cohort study.

Semaglutide is a glucagon-like peptide-1 receptor agonists (GLP-1-RAs) approved for the treatment of type 2 diabetes mellitus (T2DM) at doses up to 1 mg. The results from randomized control trials and real-world studies revealed that weekly semaglutide was associated with significant improvements in HbA1c and body weight. To our knowledge, no study assessed the effectiveness of using semaglutide for patients with T2DM in the Saudi population. We aim to assess the effectiveness of once weekly SC 0.5 and 1 mg of semaglutide on HbA1c and weight reduction in patients with T2DM in the Saudi population within 12 months of use, evaluate the predictors of response, and compare the effect of the two doses. This is a retrospective cohort study conducted at Security Force Hospital in Riyadh, Saudi Arabia. Using electronic medical records of patients with type two diabetes who received semaglutide 0.5 or 1 mg for a total duration of at least 12 months of use. Within the study period of semaglutide use, HbA1c significantly decreased from baseline by -2.1% (-2.3 to -1.91, 95% CI) (P <0.001). While the mean change in weight was -6.19kg (-6.66 to -5.72, 95% CI) (P<0.001). Moreover, BMI, FBG, total cholesterol, LDL, and TG all decreased significantly from baseline (p<0.001). When comparing the sub-groups of 0.5 and 1 mg doses, although results were numerically favorable of 1 mg, there were no statistically significant differences in HbA1c % (-2.1 ± 1.8 vs. -2.1 ± 1.9, p-value= 0.934, respectively), and weight (-6.1 ± 5 vs. -6.2 ± 4.4kg, p-value=0.837, respectively). Significant predictors of HbA1c reduction were the duration of DM, baseline HbA1c, and insulin therapy. While the significant predictor for weight reduction was insulin therapy. This study is document the effectiveness of once-weekly SC semaglutide on glycemic control and weight loss in real-world practice. We recommend a starting goal dose of 0.5 mg and gradual increase of dose based individual patient response. further studies are needed to assess the effectiveness and tolerability of various semagltude doses.

Irradiation response of microstructure and mechanical properties of NbMoVCr multi-principal element alloy coatings

In this study, NbMoVCr multi-principal element alloy (MPEA) coatings with near-equal atomic ratios were deposited onto the ferritic/martensitic (F/M) steel substrate by magnetron sputtering and then irradiated using 6 MeV Au2+ at room temperature (RT) and 550 °C, respectively. The results demonstrate that the NbMoVCr coatings have excellent irradiation resistance in terms of phase stability. RT-irradiation introduces both interstitial- and vacancy-type dislocation loops, and the dislocation loop density increases with the increase of irradiation damage dose. Meanwhile, RT-irradiation could also induce grain growth of the coating. However, under high-temperature irradiation, more recombination and annihilation of irradiation-induced defects, and recrystallization occur in the coating. In addition, irradiation also promotes the desegregation of V and Cr elements at the grain boundaries and enhances the uniformity of the distribution of coating elements. Irradiation softening and hardening in NbMoVCr coatings are also found to depend strongly on both irradiation damage dose and irradiation temperature. The creep deformation mechanism of the coating is dominated by diffusion; thus, the irradiation-enhanced diffusion reduces the creep resistance of the coating.

Somapacitan-induced reversible lipoatrophy in an adult woman with hypopituitarism

BackgroundLipoatrophy is rare adverse event (AE) in daily recombinant human growth hormone (rhGH). Data on lipoatrophy in newly developed long-acting GH (LAGH) are scarce. We report the first case of lipoatrophy in adult patient treated with LAGH somapacitan.Case presentationA 38-year-old woman with congenital panhypopituitarism was transitioned from daily rhGH 0.4 mg QD to somapacitan dose 4 mg QW due to non-adherence to daily rhGH. Despite adequate education and regular changing of injection sites, the patient reported reduced subcutaneous tissue at all four injection sites, after the 4th application of somapacitan. Somapacitan was discontinued at patient preference and lipoatrophy completely reversed after 3 months.ConclusionsLipoatrophy caused by somapacitan was completely reversible. We speculate that high initial dose and volume of somapacitan caused delayed diffusion and a direct local lipolytic effect in our patient. Although, titration of somapacitan was initiated as previously reported in REAL2 study protocol, recent clinical guidelines advise more gradual increase of somapacitan dose also in women on oral estogens that are switched from daily rhGH. Importantly, our case and the two previously described cases in children in the REAL 3 study showed that lipoatrophy caused by somapacitan was transient and completely reversible, and that discontinuation of the drug is not always mandatory.

Long-term efficacy and reduced side-effects of buprenorphine in patients with moderate and severe chronic pain.

Chronic pain significantly impacts quality of life and poses substantial public health challenges. Buprenorphine, a synthetic analog of thebaine, is recognized for its potential in managing moderate to severe chronic pain with fewer side effects and a lower incidence of tolerance compared to traditional opioids. This retrospective study aimed to assess the long-term efficacy and safety of buprenorphine transdermal patches in patients with moderate and severe chronic pain, with a focus on pain relief sustainability and tolerance development. This retrospective observational study involved 246 patients prescribed buprenorphine transdermal patches. We evaluated changes in pain intensity using the Numeric Rating Scale (NRS), assessed opioid tolerance based on FDA guidelines for morphine-equivalent doses, and measured patient-reported outcomes through the Patients' Global Impression of Change (PGIC). Any adverse events were also recorded. Over the 36-month period, there was a significant reduction in NRS scores for both moderate and severe pain patients, demonstrating buprenorphine's sustained analgesic effect. Tolerance measurement indicated that no patients required increases in morphine-equivalent doses that would meet or exceed the FDA's threshold for opioid tolerance (60mg/day of morphine or equivalent). Additionally, patient satisfaction was high, with the PGIC reflecting significant improvements in pain management and overall wellbeing. The side effects were minimal, with skin reactions and nausea being the most commonly reported but manageable adverse events. The study findings validate the long-term use of buprenorphine transdermal patches as an effective and safe option for chronic pain management, maintaining efficacy without significant tolerance development. These results support the continued and expanded use of buprenorphine in clinical settings, emphasizing its role in reducing the burdens of chronic pain and opioid-related side effects. Further research is encouraged to refine pain management protocols and explore buprenorphine's full potential in diverse patient populations.

INFLUENCE OF TAURINE ON LARVAL EYE DEVELOPMENT AND GROWTH PERFORMANCE OF GOLDEN RABBITFISH (Siganus guttatus)

ARTICLE HIGLIGHTS- Taurine improves eye development in golden rabbitfish larvae- Enhanced growth performance with taurine-enriched rotifers- Taurine positively impacts fish eye and body growthABSTRACTGolden rabbitfish (Siganus guttatus) is an emerging species for aquaculture industry, despite constrains faced on commercial scale of seed production due to the high mortality during the first-feeding stage. An experiment was conducted to determine the effect of taurine through enrichment of rotifers as live-feed on eye development and growth performance of larval golden rabbitfish. Observation of eye development was carried out by measuring eye diameter of the larva and development of the retina based on histology assessment. Growth performance was measured for absolute growth and fin development of the larvae and survival rate. The results showed that taurine-enriched rotifer generally provided better performances for eye development and growth of larval golden rabbitfish compared with control (without taurine). Increase of taurine dose up to 0.050 g/L resulted in an increase of eye diameter, absolute growth, fin development and survival rate. Further increased increment of the taurine tended to decrease the values of the measured parameters. The eye diameter of larval golden rabbitfish fed with 0.050 g/L taurine-enriched rotifer was significantly wider (106.1±9.8 µm) (P &lt; 0.05) compared with control (58.2±14.3 µm), but did not significantly differ from other doses of taurine (P &gt; 0.05). Body width of larvae fed with 0.050 g/L taurine-enriched rotifer was significantly higher (127.3±14.6 µm) (P &lt; 0.05) compared with control (98.8±18.3 µm). In regard to eye development, growth performances (total length, fin development and survival rate), dose of taurine for rotifer enrichment fed to larval golden rabbitfish Siganus guttatus was 0.050 g/L.