Full Dose Research Articles

Effect of Liquid Microbial Consortium on Physio Chemical Properties of Rice Field (Oryza Sativa) in a Vertisol

A study was conducted during kharif 2020 on "Effect of liquid microbial consortium (Azotobacter, Azospirillum, PSB (Pseudomonas mallei, Pseudomonas cepaceae, Penicillium sp.) and KSB) on physio chemical properties and microbial population of rice field (Oryza sativa) in a Vertisol" at the Indira Gandhi Krishi Vishwavidyalaya's Research cum instructional farm in Raipur (C.G.). Experiment included seven treatments viz. control (no fertilizer, no liquid NPK microbial consortia), two independent applications of 75 % RDF (90:45:30) and 100% RDF ((120: 60: 40) N, P2O5, and K2O kg ha-1 and four various combinations of seed and soil application of liquid NPK microbial consortia. Seed coating with NPK consortia @5ml kg-1, with 75% and 100% RDF and Seed coating with NPK consortia @5ml kg-1 + Soil application of NPK consortia @3 L ha-1 at 21 DAS with 75%RDF and 100%RDF. In the experiment, liquid biofertilizer products, such as liquid microbial NPK consortia were used. The population of Azotobacter, Azospirillum, phosphorous solubilizing bacteria (PSB), potassium solubilizing bacteria (KSB) and total bacterial population were significantly influenced by application of consortia as seed treatment @ 5ml kg-1 only and by a combination of seed treatment @ 5ml kg-1 seed + soil application @ 3 L ha-1 at 21 DAT with 75 or 100 % recommended dose of fertilizers and showed statistically significant higher microbial population in comparisons with the treatments of untreated alone applications of 75 or 100 % RDF. The results showed that the soil reaction, (pH) salt concentration (Electrical conductivity) and organic carbon status were not significantly influenced by the different treatments of fertilizer levels and microbial consortia applied. Slight decrease in the soil reaction (pH) and slight increase in the OC status after the harvesting of rice were observed from their initial soil values (before application of treatments). It might be due to the addition of organic matter as plant residues (straw and roots) of rice crop gown in the field. As compared to untreated- control (T1) a slight decrease in pH and increase in organic carbon content due to application of fertilizer and microbial consortia were also recorded. The residual available nitrogen in the soil after the harvesting of rice was not significantly influenced by the fertilizer levels and NPK consortia applied. The initial status of the experimental soil was low for available nitrogen (224 kg ha-1), medium for available phosphorus (24.5 kg ha-1) and high for available potassium (384 kg ha-1). Due to the addition of nitrogen through the fertilizer (90-120 kg ha-1) and less uptake of native nitrogen from the soil, a marginal increase in the residual available N in the soil from the initial level was observed in all treatments except the control (no fertilizer, no consortia). The residual status of available potassium was also not significantly influenced by the applied fertilizer doses and NPK consortia. A marginal decrease in the residual available K status after the harvesting of rice was observed in all treatments. A decrease was found in the control plot. A decrease in the K status (from the initial level) was observed less where a full dose of NPK fertilizers (100%) was applied with the NPK consortia. Ramlakshmi et al. [1], also observed slight reduction in soil pH and increase in organic carbon content in biofertilizer inoculated treatments as compared to the un-inoculated control soil [2].

Yield and Nitrogen Uptake of Wheat as Influenced by Nitrogen, Vermicompost and Biofertilizer Application at Rampur, Chitwan, Nepal

High cost, unavailability, and imbalance use of chemical fertilizers and environmental degradation are challenging sustainability of wheat production in Nepal. Integration of vermicompost, biofertilizer (Azotobacter chrococcom) and chemical fertilizer can improve the situation. A field experiment was conducted to assess the combined application of vermicompost, chemical fertilizer and biofertilizer on the growth, yield, and nitrogen uptake of wheat at Rampur Chitwan from November 2021 to April 2022. The experiment was laid out in a strip-split plot design with five N levels as horizontal factors (0, 25, 50, 75, and 100% of recommended dose), two vermicompost levels (0 and 5 t ha-1) as the vertical factor, and two biofertilizer levels (with and without application) as the sub-plot factor with three replications. Data on growth, yield attributes and yield of wheat, nitrogen uptake were collected, analyzed and presented. The research result revealed a significant influence of biofertilizer and nitrogen levels on grain yield of wheat. Full dose of nitrogen resulted a significantly higher grain yield (4441.71 kg ha-1) than other nitrogen levels (0, 25, 50, 75 % of recommended dose with grain yield 2792.11, 2982.20, 3771.17. 4231.63 kg ha-1 respectively). Biofertilizer application had significantly higher grain yield (3726.76 kg ha-1) compared with no biofertilizer application (3560 kg ha-1). There was significant interactions between biofertilizer application and nitrogen levels on number of grains per spike and sterility percent of wheat. The number of grain per spike was highest with 100% recommended N with biofertilizer application (47.52 grains/spike) followed by 75 % recommended N with biofertilizer application (46.53 grains/spike). The sterility % was lowest (6.47 %) with 100 % N with biofertilizer application followed by 75 % N with biofertilizer application (6.72 %). Total nitrogen uptake was significantly higher (119.04 kg ha-1) for full dose of nitrogen as compared with lower nitrogen levels (0, 25. 50, 75 % recommended N levels). Biofertilizer application also resulted in significantly higher nitrogen uptake (89.89 kg ha-1) as compared with no Biofertilizer application (79.89 kg ha-1). Integration of biofertilizer, with chemical fertilizer 75 - 100 % recommended N level could increase the growth, yield, and nitrogen uptake of wheat in Chitwan.

Therapeutic Drug Monitoring of Elexacaftor, Tezacaftor, and Ivacaftor in Adult People with Cystic Fibrosis.

Elexacaftor, tezacaftor, and ivacaftor (ETI) have significantly improved lung function in people with cystic fibrosis (pwCF). Despite exceptional improvements in most cases, treatment-related inter-subject variability and drug-drug interactions that complicate modulator therapy have been reported. This retrospective analysis presents data on the serum concentration of ETI in our pwCF with full or reduced dosage from August 2021 to December 2023 via routine therapeutic drug monitoring (TDM). The data were compared with the maximum drug concentrations (Cmax) from the pharmaceutical company's summary of product characteristics. A total of 786 blood samples from 155 pwCF (41% female, 59% male) were analyzed. The examinations were divided into four groups: full dose within the given tmax (38.5% of all measurements), full dose outside the tmax (29%), reduced dose within the tmax (19.2%), and reduced dose outside the tmax (13.2%). In pwCF receiving the full dose and blood taken within the tmax, 45.3% of serum concentrations of elexacaftor, 51.1% of serum concentrations of ivacaftor, and 8.9% of serum concentrations of tezacaftor were found to be above the Cmax, respectively. For those on reduced doses within the tmax, 24.5% had a serum concentration of elexacaftor, 23.2% had a serum concentration of ivacaftor, and 2.5% had a serum concentration of tezacaftor above the Cmax, respectively. Many pwCF under ETI therapy have Cmax values for elexacaftor and ivacaftor above the recommended range, even on reduced doses or before the tmax was reached. This highlights the value of a TDM program. Further pharmacokinetic studies are necessary.

The Efficacy and Safety of Stepwise Oral Food Challenge in Children with Cow’s Milk Allergy

Plain Language SummaryStepwise oral food challenge (OFC) tests begin with low doses of allergens, progressing to full doses. This is one of the strategies used to avoid anaphylactic reactions to the reintroduction of allergens. We previously reported the safety and efficacy of hen egg OFC. In this study, we discuss it for cow’s milk (CM) allergy. We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (<10 mL), middle (≥10 mL but <100 mL), or full. When the participants reacted to low doses, they underwent very low-dose OFC using baked milk or <1 mL of CM. Positive reactions developed in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results and anaphylaxis. Multivariate analysis indicated that only in low-dose OFCs, higher CM-specific IgE (CM-sIgE) levels, younger age, and complete CM elimination were associated with positive OFC results. Food ladders, an approach to reintroduce allergens, are becoming increasingly popular. Although we believe that OFC is a safer strategy to reintroduce CM to children with CM allergy, our CM-OFCs appeared to develop more anaphylactic reactions than milk ladders. The stepwise OFC reintroduced small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at a younger age, preferably from infancy, with very low doses, similar to milk ladders, may facilitate the safe reintroduction of CM.

Hematologists' state of knowledge on practical aspects of hemophagocytic lymphohistiocytosis (HLH) in adult patients: A Young Hematologists' Club survey.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome with various etiologies. Its treatment is complicated by several important but not immediately obvious issues (e.g., HLH-2004 criteria are the most commonly used for diagnosis, but the recommended therapeutic regimen is HLH-94). The study aimed to assess hematologists' practical knowledge of HLH. A survey was conducted among physicians treating adult hematological patients. A 10-question paper questionnaire was distributed to physicians from various hematology centers. A total of 126 questionnaires were analyzed. Most respondents had little-to-moderate experience in caring for HLH patients: 59% treated 0-2 patients and 36% treated between 3-5 patients. Among the respondents, the preferred diagnostic criteria were HLH-2004, either in its original form (5 out of 8 criteria) for 70 respondents or its modified version (4 out of 6 available criteria when ferritin exceeds 2,000 ng/mL) for 56 respondents. The preferred treatment regimen was HLH-2004, with a full dose of etoposide in 72 responses or reduced in 39 responses. Fifty percent of respondents incorrectly answered that meeting the HLH-2004 criteria necessitates the use of the HLH-94/2004 regimen in full doses and duration. Sixty-four percent of respondents correctly identified that hemophagocytosis is not necessary for the diagnosis. This survey reveals that the majority of surveyed physicians adhere to international HLH recommendations. However, there are instances where these guidelines are not fully implemented, which underlines the need for further efforts to raise awareness and share clinical experiences about this patient group.

Attenuated neutralization, maintained specificity: Humoral response to SARS-CoV-2 booster in kidney allograft recipients

Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.

Automated assessment of task-based performance of digital mammography and tomosynthesis systems using an anthropomorphic breast phantom and deep learning-based scoring.

Conventional metrics used for assessing digital mammography (DM) and digital breast tomosynthesis (DBT) image quality, including noise, spatial resolution, and detective quantum efficiency, do not necessarily predict how well the system will perform in a clinical task. A number of existing phantom-based methods have their own limitations, such as unrealistic uniform backgrounds, subjective scoring using humans, and regular signal patterns unrepresentative of common clinical findings. We attempted to address this problem with a realistic breast phantom with random hydroxyapatite microcalcifications and semi-automated deep learning-based image scoring. Our goal was to develop a methodology for objective task-based assessment of image quality for tomosynthesis and DM systems, which includes an anthropomorphic phantom, a detection task (microcalcification clusters), and automated performance evaluation using a convolutional neural network. Experimental 2D and pseudo-3D mammograms of an anthropomorphic inkjet-printed breast phantom with inserted microcalcification clusters were collected on clinical mammography systems to train a signal-present/signal-absent image classifier based on Resnet-18 architecture. In a separate validation study using simulations, this Resnet-18 classifier was shown to approach the performance of an ideal observer. Microcalcification detection performance was evaluated as a function of four dose levels using receiver operating characteristic (ROC) analysis [i.e., area under the ROC curve (AUC)]. To demonstrate the use of this evaluation approach for assessing different technologies, the method was applied to two different mammography systems, as well as to mammograms with re-binned pixels emulating a lower-resolution X-ray detector. Microcalcification detectability, as assessed by the deep learning classifier, was observed to vary with the exposure incident on the breast phantom for both DM and tomosynthesis. At full dose, experimental AUC was 0.96 (for DM) and 0.95 (for DBT), whereas at half dose, it dropped to 0.85 and 0.71, respectively. AUC performance on DM was significantly decreased with an effective larger pixel size obtained with re-binning. The task-based assessment approach also showed the superiority of a newer mammography system compared with an older system. An objective task-based methodology for assessing the image quality of mammography and tomosynthesis systems is proposed. Possible uses for this tool could be quality control, acceptance, and constancy testing, assessing the safety and effectiveness of new technology for regulatory submissions, and system optimization. The results from this study showed that the proposed evaluation method using a deep learning model observer can track differences in microcalcification signal detectability with varied exposure conditions.

Long-Term Manuring and Fertilization Influence on Soil Properties and Wheat Productivity in Semi-Arid Regions

Information on the long-term effects of the addition of organics and fertilizers to wheat under the pearl millet–wheat cropping system with semi-arid conditions in north-western India is still lacking. The present research was conducted in an ongoing field experiment initiated during Rabi 1995 at the Research Farm of Chaudhary Charan Singh at Haryana Agricultural University, Hisar. After 25 years, the impacts of nutrient management practices on soil fertility and wheat productivity were evaluated. The experiment comprised a total of eight treatment combinations viz. half and full doses of recommended fertilizers (N and P), organic manures (FYM: farmyard manure, POM: poultry manure, and PRM: press mud) alone and in combination with NP fertilizers. The conjoint application of organic manure and chemical fertilizers resulted in a positive influx of nutrients via increasing total organic carbon (TOC), available N, P, K, and S, which ranged from 0.46 to 1.42%, 122.70 to 194.70, 15.66 to 74.92, 340.5 to 761.2, and 15.26 to 54.63 kg ha−1 in surface soil (0–15 cm), respectively. Carbon fractions and crop yield were significantly improved by adopting integrated nutrient management (INM). The TOC showed a positive and significant correlation with C fractions (r &gt; 0.92) and with soil-available N, P, K, and S (r &gt; 0.77) content. The data also revealed a strong relationship between TOC and soil-available (0–15 cm) nutrients i.e., available N (R2= 0.769), available P (R2 = 0.881), available K (R2 = 0.758), and available S (R2 = 0.914), respectively. Thus, practices that increased TOC were also beneficial in enhancing the availability of the nutrients in the soil. A positive and highly significant correlation was also found among wheat yield, nutrient (NPKS) content, and uptake. A polynomial relationship between grain yield and grain N (R2 = 0.962), P (R2 = 0.946), and K (R2 = 0.967) content, and between straw yield and straw N (R2 = 0.830), P (R2 = 0.541) and K (R2 = 0.976) content was obtained. Integrated use of PRM7.5 followed by FYM15 and POM5 coupled with NP fertilizers proved best, which could be beneficial for obtaining nutritious and highest wheat yield (grain: 6.01 t ha−1 and straw: 7.70 t ha−1) coupled with improved fertility within a sustained manner under the pearl millet–wheat sequence in prevailing semi-arid conditions of the North Indian state of Haryana.

The correlation between rituximab dose reduction and acute relapses of neuromyelitis optica spectrum disorder, lessons from COVID-19 epidemic

BackgroundCOVID-19 was a viral infection that led to a global pandemic in March 2020. At the beginning of the pandemic, clinicians encountered the challenge of how immunosuppressive treatments would affect the course of COVID-19 infection in people with autoimmune diseases. Neuromyelitis optica spectrum disorder is an autoimmune astrocytopathy that is caused by an inflammation in the CNS. Major treatments to prevent acute relapses include immunosuppressive drugs. Rituximab is a well-established immunosuppressive agent in NMOSD maintenance therapy. Some reports suggested that treatment with Rituximab might increase the risk of COVID-19 infection and its mortality in NMOSD. On the other hand, dose reduction or extended interval treatment might lead to acute relapses of NMOSD and permanent disability. MethodsIn this study, we evaluated the correlation between the dose of rituximab and the relapse rate of NMOSD during an epidemic. This was an observational study on 171 patients among whom 55 cases were seropositive. Some patients received full dose rituximab routinely (1000 mg/dose, every 6 months), but others were treated with half dose (500 mg/dose) during the epidemic. Also, some doses were prescribed with a delay, based on the level of CD19 and CD20. ResultsThe Pearson correlation coefficient (r) showed a negative and significant relation (r: - 0.19, p: 0.022) between the amount of drug and the number of relapses in the seropositive group, so low dosage of the drug was related to more acute relapses. In seronegative cases, there was not any valuable relationship. (p: 0.367). ConclusionLower dose of rituximab, especially in seropositive NMOSD patients, can potentially lead to acute relapses. So, the more frequent evaluation of the CD19, CD20, and, CD27 levels, and the general clinical condition of the patients should be considered.

Impact of Plant Growth Promoting Endophytic Bacterial Consortia on Biochemical Parameters of Maize under Moisture Stress Conditions in In vitro

Mitigation strategies based on plant–microbe interactions to increase the performance of plants under water-deficit conditions are well documented. However, little is known about a suitable consortium of bacterial inoculants and underlying physiological and enzymatic events to improve drought tolerance in maize. This study aimed to investigate the synergistic interactions among plant growth-promoting bacteria to alleviate drought-induced damages in maize. In pot culture experiment endophytic bacterial consortium inoculated treatments imposed with moisture stress (75% water holding capacity) with full dose (T9) and 75% recommended dose of fertilizers (T8) were found to excel in many plant biochemical properties when compared to un-inoculated control. For instance chlorophyll stability index T9 (138.67%) T8 (133.33%), relative water content T9 (95.20%), The N, P and K uptake was found significantly higher in T9 with 13.98 g plant-1, 3.38 g plant-1 and 17.29 g plant-1 respectively. Thus, the current research advocates the use of endophytic microbial consortium to mitigate moisture stress and to improve plant biochemical properties which ultimately enhances the plant health and yield.

6866 Real-world implications and limitations of GLP-1 prescriptions in adolescents

Abstract Disclosure: G. Castano: None. S. Sisley: None. Background: Glucagon-like-peptide-1 agonists (GLP1), approved for adolescents ≥ 10 years in 2019 for type 2 diabetes (T2D) and ≥ 12 years in 2020 for obesity, require adequate dose titration and have known side effects. There is little information on insurance approval, adherence to titration regimens, or the side effects of liraglutide in clinical practice. Methodology: We performed a retrospective review of all patients &amp;lt;18 years old who were prescribed GLP-1 at a large children’s hospital. We collected demographic information, prescription orders, insurance approval, and drug initiation dates. For individuals who completed at least 26±8 weeks of treatment, we also collected dose titration, side effects, and insulin doses. Results:599 patients were prescribed GLP-1 from 2019 to 2023, with a mean age of 14.99±2.1 years, 58% female, 58% public insurance, and 74% (n=442) with T2D. The cohort was comprised of 63% White, 30% Black, and 2.3% Asian individuals, with 52% of Hispanic ethnicity. 90% of prescriptions were for liraglutide, and 10% for other GLP1 analogs, including exenatide, dulaglutide, and semaglutide. Insurance denied 41% (n=244) of prescriptions, with more denials in those without T2D, 64% vs 32% in patients with T2D.Whereas private insurance denied more prescriptions than Medicaid in patients with T2D (54% vs 27%), the reverse was true for patients without T2D ( 55% private vs 69% Medicaid). Patients lost to follow-up in the first 3 months accounted for 22% (n=135) of the cohort, even though 48% (n=66) of those patients had insurance approval.Those who had insurance approval and took liraglutide for at least 26 weeks accounted for 34% (n=204) of the cohort. Of the patients with T2D, 50% (n=95) titrated to 1.8mg by their first follow-up appointment (1-3 months after prescription start), 33% (n=62) by 6 months, and 17% (n=32) never reached 1.8mg. In patients prescribed a higher dose of liraglutide (3.0 mg daily), 42% (n=8) titrated to 3mg over 5 weeks as prescribed, and 52% (n=10) never reached 3mg, with only one of them not reaching 1.8 mg.Most patients (82%, n=169) had no side effects documented in their charts. From those with side effects reported, GI problems (nausea, vomiting, diarrhea) were noted in 12% (n=25), and 2% (n=4) reported injection site reactions. Side effects that required medication discontinuation included hypoglycemia (n=1), mild pancreatitis (n=1), and severe pancreatitis (n=2). Conclusion: In clinical practice, despite FDA approval, insurance coverage of liraglutide is limited. Almost half of the patients require extra time to reach full doses of liraglutide, with one-third never reaching full treatment doses. Severe pancreatitis may be a previously unpublished side effect. More research is needed to understand how real-world adherence and side effects of liraglutide affect clinical outcomes. Presentation: 6/1/2024

7507 Early Detection of Hyperglycemia Using CGM Despite Reduced Dosing of Teprotumumab

Abstract Disclosure: L. Needleman: None. S.H. Kim: None. A.L. Kossler: None. C. Dosiou: None. Background: In a previous longitudinal observation study, we showed that patients with prediabetes increased HbA1c by a mean of 0.7% and 30% progressed to type 2 diabetes after treatment with teprotumumab for 3 months, or after 4 infusions [1]. However, temporal effects of hyperglycemia and the impact of lower doses of teprotumumab on hyperglycemia are unknown. Clinical case: An 86-year-old woman was diagnosed with Graves’ disease after evaluation for palpitations showed undetectable TSH, free T4 2.31 ng/dL (ref. 0.8-1.8 ng/dL), total T3 252 ng/dL (ref. 76-181 ng/dL), and elevated TSI (5.0, ref. &amp;lt;1.3). Thyroxine levels normalized four weeks after starting methimazole. Nine weeks after the initial presentation she developed diplopia and bilateral proptosis. She was diagnosed with active moderate-to-severe thyroid eye disease (CAS 4/7) and was started on teprotumumab 10 mg/kg intravenously every three weeks. The dose was not increased to 20 mg/kg due to concern for adverse effects given the patient’s age and underlying hearing impairment. At baseline, she had prediabetes based on a HbA1c of 6.0%. Additional risk factors for type 2 diabetes included older age and Asian race [1]. Continuous glucose monitoring (CGM, Dexcom G7) before starting teprotumumab showed 71% time in tight range (TITR, 70-140 mg/dL) with average fasting glucose of 115 mg/dL. Prior to starting teprotumumab, she received counseling for lifestyle modification including carbohydrate moderation. Ten days following her first teprotumumab dose, her TITR reduced to 66%. After three doses of teprotumumab, her proptosis improved by 2 mm, CAS decreased to 1/7, and diplopia resolved. However, the TITR was 59% and average fasting glucose increased to 128 mg/dL. HbA1c also increased to 7.4% and the patient was started on metformin. Conclusion: In this case, teprotumumab increased glucose as early as after the first infusion. Glucose tolerance continued to worsen with subsequent doses, with development of type 2 diabetes, even with reduced dosage of teprotumumab. This case demonstrates that monitoring for teprotumumab-related hyperglycemia can be optimized with use of CGM and that lower doses of teprotumumab do not eliminate the risk of worsening glucose tolerance. Whether hyperglycemia would have been more severe with full dose teprotumumab remains uncertain. Reference: [1] Amarikwa L, Mohamed A, Kim SH, Kossler AL, Dosiou C. Teprotumumab-Related Hyperglycemia. J Clin Endocrinol Metab. 2023 Mar 10;108(4):858-864. Presentation: 6/3/2024

The impact of starting dose on overall survival in myelofibrosis patients treated with ruxolitinib: A prospective real-world study on AIFA monitoring registries.

Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of myelofibrosis (MF)-related splenomegaly or symptoms. The recommended starting dose depends on platelet count, regardless of haemoglobin level at baseline. In the recent years, an overall survival (OS) advantage was reported in patients treated with ruxolitinib compared with best available therapy. We analysed a large Italian cohort of 3494 patients identified by Agenzia Italiana del Farmaco (AIFA) monitoring registries. Of them, 2337 (66.9%) started at reduced dose: these patients were older (median age 70 vs. 67), with increased incidence of large splenomegaly (longitudinal diameter 20 vs. 19.1 cm, median volume 1064 cm3 vs. 1016 cm3), with higher IPSS risk (30.9% vs. 26.1%), and worse ECOG score (more than 1 in 14.3% vs. 9.8%). After balancing for baseline characteristics, Kaplan-Meier analysis showed a median OS of 78.2 months (95% CI 65.9-89) for patients who started at full dose and 52.6 (95% CI 49-56.6) months for patients who started with reduced dose (p < 0.001). Group analysis also showed a substantial difference in patients with intermediate-2 and high IPSS risk. The majority of MF patients in real-world analysis started with a reduced dose of ruxolitinib, which is associated with less favourable outcomes.

Deep learning-based multi-frequency denoising for myocardial perfusion SPECT

BackgroundDeep learning (DL)-based denoising has been proven to improve image quality and quantitation accuracy of low dose (LD) SPECT. However, conventional DL-based methods used SPECT images with mixed frequency components. This work aims to develop an integrated multi-frequency denoising network to further enhance LD myocardial perfusion (MP) SPECT denoising.MethodsFifty anonymized patients who underwent routine 99mTc-sestamibi stress SPECT/CT scans were retrospectively recruited. Three LD datasets were obtained by reducing the 10 s acquisition time of full dose (FD) SPECT to be 5, 2 and 1 s per projection based on the list mode data for a total of 60 projections. FD and LD projections were Fourier transformed to magnitude and phase images, which were then separated into two or three frequency bands. Each frequency band was then inversed Fourier transformed back to the image domain. We proposed a 3D integrated attention-guided multi-frequency conditional generative adversarial network (AttMFGAN) and compared with AttGAN, and separate AttGAN for multi-frequency bands denoising (AttGAN-MF).The multi-frequency FD and LD projections of 35, 5 and 10 patients were paired for training, validation and testing. The LD projections to be tested were separated to multi-frequency components and input to corresponding networks to get the denoised components, which were summed to get the final denoised projections. Voxel-based error indices were measured on the cardiac region on the reconstructed images. The perfusion defect size (PDS) was also analyzed.ResultsAttGAN-MF and AttMFGAN have superior performance on all physical and clinical indices as compared to conventional AttGAN. The integrated AttMFGAN is better than AttGAN-MF. Multi-frequency denoising with two frequency bands have generally better results than corresponding three-frequency bands methods.ConclusionsAttGAN-MF and AttMFGAN are promising to further improve LD MP SPECT denoising.

Palliative care in patients with hepatocellular carcinoma: Results from a survey among hepatologists and palliative care physicians

Background: Delays and limitations of palliative care in patients with liver transplantation-ineligible end-stage hepatocellular carcinoma according to Barcelona Clinic Liver Cancer staging system may be explained by different perceptions between hepatologists and palliative care physicians in the absence of shared guidelines. Aim: To assess physicians’ attitudes toward palliative care in end-stage hepatocellular carcinoma and to understand what the obstacles are to more effective management and co-shared between palliative care physicians and hepatologists. Design: Members of the Italian Association for the Study of Liver Disease and the Italian Society of Palliative Care were invited to a web-based survey to investigate practical management attitude for patients with liver transplant-ineligible end-stage hepatocellular carcinoma. Participants: Physician members of the of the two associations, representing several hospitals and services in the country. Results: Ninety-seven hepatologists and 70 palliative care physicians completed the survey: >80% regularly follow 1–19 patients; 58% of hepatologists collaborate with palliative care physicians in the management of patients, 55% of palliative care physicians take care of patients without the aid of hepatologists. Management of cirrhosis differed significantly between the two groups in terms of prescription of albumin, esophagogastroduodenoscopy, anti-viral treatment, anticoagulation, indication to paracentesis and management of encephalopathy. Full-dose acetaminophen is widely used among hepatologists, while opioids are commonly used by both categories, at full dosage, regardless of liver function. Conclusions: This survey highlights significant differences in the approach to patients with liver transplantation-ineligible end-stage hepatocellular carcinoma, reinforcing the need for shared guidelines and further studies on palliative care in the setting.

Functional brain connectivity predictors of prospective substance use initiation and their environmental correlates

BackgroundEarly substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the maturation of brain networks, the pace and magnitude of which are susceptible to environmental influences and may shape risk for SUI. MethodsWe examined whether patterns of functional brain connectivity during rest (rsFC), measured longitudinally in pre-and-early adolescence, can predict future SUI. Next, in an independent sub-sample, we tested whether these patterns are associated with earlier environmental exposures, specifically neighborhood pollution and socioeconomic dimensions. We utilized data from the Adolescent Brain Cognitive Development (ABCD) Study®. SUI was defined as first-time use of at least one full dose of alcohol, nicotine, cannabis, or other drugs. We created a control group (N = 228) of participants without SUI who were matched with the SUI group (N = 233) on age, sex, race/ethnicity, and parental income and education. ResultsMultivariate analysis showed that whole-brain rsFC from 9-10 to 11-12 years of age (prior to SUI) prospectively differentiated the SUI and control groups. The SUI-related rsFC pattern was also related to aging in both groups, suggesting a pattern of accelerated maturation in the years prior to SUI. This same pattern of rsFC was predicted by higher pollution, but not neighborhood disadvantage (adjusted for family socioeconomic factors) in an independent sub-sample (N = 2,854). ConclusionBrain functional connectivity patterns in early adolescence that are linked to accelerated maturation can predict SUI in youth and are associated with exposure to pollution.

Transverse interlaminar ultrasound-guided C1-C2 puncture for the intrathecal administration of nusinersen in patients with spinal muscular atrophy.

Severe spinal deformities and previous spinal orthopedic instrumentation may result in substantial technical challenges for nusinersen delivery through lumbar puncture in patients with spinal muscular atrophy (SMA). The aim of this paper was to review our experience with ultrasound-guided cervical puncture as an alternative approach for the intrathecal administration of nusinersen. This was a retrospective medical record review of transverse interlaminar ultrasound-guided C1-C2 puncture for nusinersen delivery in SMA patients. The details of puncture, complications, and success rate of the procedure were summarized. There were four patients who received a total of 13 cervical punctures for nusinersen delivery. All procedures were technically successful with no major complications. Full doses of nusinersen were delivered intrathecally. Transverse interlaminar ultrasound-guided C1-C2 puncture is an alternative approach for administering nusinersen if lumbar puncture fails. The success of the technique requires a thorough preprocedural evaluation of cervical spine imaging, sound knowledge of the cervical sonoanatomy and careful manipulation of the needle.

Potentially Inappropriate Medications and De-prescribing: An Audit of STOPP/START on an Inpatient Rehabilitation Ward

Abstract Background Polypharmacy is well recognized in older adults with many adverse outcomes. Practical tools, such as the ‘STOPP/START’ criteria, aid clinicians in de-prescribing to tackle medication related morbidity. Current research suggests these tools are insufficiently implemented in clinical practice (1). Many older adults require rehabilitation after acute hospital admissions which can provide an ideal setting for medication review and de-prescribing. Methods A retrospective audit was carried out of 35 older adults in a gerontological inpatient rehabilitation facility between 8th February and 8th April 2024. Demographic and clinical data was collected using electronic and handwritten patient records. Each patients’ medication prescription was reviewed from date of admission to rehabilitation facility. Number of medications prescribed was recorded. Using the ‘STOPP/START’ criteria, potentially inappropriate medications (PIMs were identified, and de- prescribing was noted for the PIM where taken. Results 35 patients were included in the study. No patient was excluded. Mean age was 86.14 years and mean number of prescribed medications per patient was 11. The most common presenting complaint was a fall in 57.14% of patients, in which 95% had acute fracture. Other presenting complaints for acute admission included delirium and infection. Mean clinical frailty score was 5.71. 38 PIMswere identified, totalling 10% of all medication prescriptions. Of these, 12 de-prescribing opportunities were taken, one of which was a dose reduction. The most common PIMswere prescribing of PPI at full therapeutic dose (n=12), inappropriate opioid prescribing (n=4) and hypnotics (n=7) in high-risk groups. Conclusion Polypharmacy and PIMsare common in older adults and are related to adverse outcomes, especially in frail adults at risk of falls, fracture, and delirium. The rehabilitation setting is an ideal location for use of de-prescribing tools however their implementation varies. This may be improved by education and structured medication review in collaboration with trained pharmacists.

Comparison of Hounsfield Unit variability between two same model photon counting CT detector systems. A phantom study applied to lung CT

Accurate quantification of lung density, in Hounsfield Units (HU), is of high importance to monitor progression of diseases such as emphysema using chest CT imaging. Reproducibility of HU quantification on independent photon counting detector CT (PCD-CT) systems with a focus on lung imaging have not yet been evaluated. We thus aimed to evaluate HU reproducibility on 2 independent PCD-CT systems using a repeatable phantom setup with identical acquisition and image reconstruction settings. A COPDGene phantom comprising densities of air, water and lung was scanned on 2 independent PCCT systems using 3 different radiation exposures, 2 medium-sharpness reconstruction kernels (Br40 and Qr36), with and without iterative reconstruction (levels 0 vs 3). Our results demonstrate that acquisitions performed with full dose (3.2 mGy), half dose (1.6 mGy), and one-eighth dose (0.4 mGy) had minimal influence on HU accuracy (<6 HU) when using Br40 and Qr36 kernels. The level of iterative reconstruction also has a minimal impact (<6 HU) with the same kernels. Between the 2 PCD-CT systems evaluated, reproducible HU quantification was achieved for changes to CTDIvol, iterative reconstruction level and reconstruction kernel.

The recurrence of disease activity after ocrelizumab discontinuation in multiple sclerosis

IntroductionOcrelizumab (OCR) is a highly effective treatment of multiple sclerosis (MS), and B cell repopulation profiles suggest that it might be used as an immune reconstitution therapy. However, data on disease recurrence after stopping treatment with OCR are scarce. Our objective was to evaluate the recurrence of disease activity after OCR discontinuation. MethodsIn this multicenter retrospective cohort study, we included MS patients who discontinued OCR, without switching to another treatment, for twelve months or more, after having received at least one full dosage of 600 mg. We defined focal inflammation as the occurrence of a clinical relapse or significant MRI activity (≥3 new T2 lesions or ≥2 contrast-enhancing lesions). ResultsWe included 53 MS patients; 41 relapsing remitting (RRMS), 5 secondary progressive (SPMS) and 7 primary progressive (PPMS) patients. Median follow-up period after OCR discontinuation was 16 months. We only observed focal inflammation after discontinuation in RRMS patients; 2.4 % (1/41) patients presented with significant MRI activity and matching clinical symptoms, and 7.3 % (3/41) patients presented with a suspected clinical relapse without radiological activity: a total of 9.8 % (4/41) at a median time of 17 months after the last infusion. DiscussionWe found focal inflammation after discontinuation of OCR in 4 (9.8 %) of the RRMS patients, of which 1 was radiologically confirmed. Our observations highlight that recurrence of focal inflammation seems low but discontinuation may not be appropriate for everyone. Further larger studies are important to determine the immune reconstitution therapy potential of OCR.