To investigate, in early rheumatoid arthritis, whether bridging with glucocorticoids (GCs) is associated with an increased risk of flare following GC tapering and withdrawal. A total of 810 NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR)patients were included in this post hoc analysis: all received methotrexate (MTX), in addition to which 135 patients received oral GC bridging therapy ('oral GC group'); 80 received intra-articular (IA) GC bridging therapy, sulfasalazine and hydroxychloroquine ('injection GC group'); and 595 received one of three (certolizumab pegol, abatacept and tocilizumab) biologic disease-modifying antirheumatic drugs (bDMARDs), hereafter the ('bDMARD group'). Clinical disease activity index (CDAI) flares (≥4.5 increase in CDAI score) were assessed longitudinally. Up to 48 weeks, flare occurred at least once in 43% of oral GC, 24% of injection GC and 28% of bDMARD patients. Over-time relative risk (RR) was higher with oral GC bridging (adjusted RR, 1.54; 95% CI, 1.16-2.03) but similar with injection GC bridging (adjusted RR 0.93; 95% CI, 0.54-1.55) versus bDMARD. Flare rates were numerically higher in the oral GC versus bDMARD group at all time points (12, 24, 32, 40 and 48 weeks), with a significant difference at w.40, the visit after protocol-defined GC discontinuation; at this visit 27% of patients who discontinued GC experienced flare; 29% among those in remission; 33% remained on low-dose prednisolone at 48weeks. Discontinuation of oral GC bridging therapy on background MTX is associated with increased flare risk, even among patients in remission. Flare rates with IA GC bridging plus triple therapy did not differ from the bDMARD group. EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.

Role of immunotherapy in the management of oral squamous cell carcinoma - A systematic review.

National data on clinical pharmacy implementation can inform health policy, resource allocation, workforce planning, and academic development. In Chile, such data are limited, particularly for therapeutic drug monitoring (TDM). The objective of this study was to characterize the clinical pharmacy workforce in Chilean hospitals and describe the implementation of core clinical activities, with an emphasis on TDM. A national cross-sectional survey was conducted among pharmacists performing clinical functions in Chilean hospitals, using the 2024 registry of the Clinical Pharmacy Division of the Chilean Society of Intensive Care Medicine as the sampling frame. Descriptive analyses were performed; workforce capacity was expressed as full-time equivalents (FTEs) and regional density per 10 000 inhabitants. Of 220 invited pharmacists, 181 responded (82.3%), representing 83 institutions across 15 of 16 administrative regions. Median age was 35 years (interquartile range [IQR] 31-39); 28.2% were registered Clinical Pharmacy Specialists, and 77.1% worked in public hospitals. The highest density was in the Metropolitan Region (0.12 FTE/10000 inhabitants), followed by Tarapacá and Antofagasta (0.09 each). Deployment was most frequent in Infectious Diseases (36.5%) and intensive care units (34.8%). Pharmacotherapy follow-up and medication therapy review were each reported by 94.5%, adverse drug reaction reporting by 87.3%, and involvement in TDM by 85.1%. Teaching and research were reported by 44.8% and 30.4%, respectively, but 95.5% reported no formally protected time. TDM was available in 81.9% of centers, most commonly for vancomycin (80.7%), valproic acid (63.9%), amikacin (60.2%), and phenytoin (57.8%); pharmacokinetic software to support dose individualization was used in 61.4% of centers. Clinical pharmacy services in Chile are broadly integrated into hospital care-particularly in infectious diseases, critical care, and TDM-while gaps persist in formal credentialing, regional workforce distribution, and institutional structures supporting academic activities.

Pazopanib for recurrent central nervous system solitary fibrous tumors: A single-institution retrospective series.

Nivolumab plus ipilimumab and cobimetinib in previously treated microsatellite-stable/DNA mismatch repair-proficient metastatic colorectal cancer: the phase II CheckMate 142 trial.

Although Graves' orbitopathy (GO) in childhood is generally considered milder than in adults, data regarding its clinical course and relationship with thyroid autoimmunity remain limited. This study aimed to evaluate the frequency and clinical characteristics of GO in pediatric patients with newly diagnosed hyperthyroidism and to assess short-term changes in ocular findings during follow-up. In this prospective observational study, 24 children with hyperthyroidism were enrolled. All ophthalmologic examinations were performed by the same ophthalmologist. Ocular findings were assessed according to the 2021 EUGOGO criteria, and disease activity was determined using the Clinical Activity Score (CAS). Thyroid function tests and autoantibodies, including anti-thyroid peroxidase antibody, thyrotropin receptor antibody, and thyroid-stimulating immunoglobulin, were evaluated at baseline and at 6months. Associations between clinical, biochemical, and ophthalmologic parameters were analyzed statistically. The mean age was 14.1±3.4 years, and 75 % of patients were female. At baseline, 83.3 % had mild GO and 16.7 % had moderate-to-severe disease. CAS values were <3 at both time points in all patients, and no active orbitopathy was observed. Hertel measurements showed no significant changes during follow-up. Significant reductions in anti-thyroid peroxidase antibody, thyrotropin receptor antibody, and thyroid-stimulating immunoglobulin levels were observed at 6months. Baseline Hertel values correlated positively with thyrotropin receptor antibody levels. Beta-blocker requirement decreased from 66.7 % at baseline to none at 6months. Only one patient (4.2 %) showed transient progression in EUGOGO severity. In pediatric hyperthyroidism, GO is usually mild and inactive, with rare short-term clinical progression. Despite marked improvement in thyroid autoimmunity, ocular findings remained largely stable. These results support the generally benign course of childhood GO and emphasize the importance of detailed ophthalmologic assessment at diagnosis.

Biliary tract cancers (BTCs) are a group of highly aggressive malignancies with limited therapeutic options. Gemcitabine plus cisplatin (GemCis) remains the standard first-line regimen; however, the efficacy of currently recommended second-line therapies remains unsatisfactory. Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 or its ligand (PD-1/PD-L1) have demonstrated antitumor activity in a subset of patients with BTC, while albumin-bound paclitaxel (nab-paclitaxel) has shown efficacy across multiple solid tumors. This study aimed to evaluate the real-world safety and efficacy of a second-line combination regimen comprising PD-1/PD-L1 inhibitors, nab-paclitaxel, and fluorouracil-based agents (capecitabine or S-1) in patients with advanced BTCs. This retrospective study included patients with advanced BTCs who received second-line therapy with a combination of PD-1/PD-L1 inhibitors, nab-paclitaxel, and fluorouracil-based agents (capecitabine or S-1) at the Second Affiliated Hospital of Nanchang University between January 2019 and May 2025. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and treatment-related adverse events (TRAEs) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and TRAEs. A total of 36 patients were enrolled, including 17 (47.2%) with gallbladder cancer, 17 (47.2%) with intrahepatic cholangiocarcinoma, and 2 (5.6%) with extrahepatic cholangiocarcinoma. According to RECIST version 1.1, no complete responses (CR) were observed; four patients (11.1%) achieved a partial response (PR), 19 (52.8%) had stable disease (SD), and 13 (36.1%) experienced progressive disease (PD), yielding an ORR of 11.1% and a disease control rate (DCR) of 63.9%. The median progression-free survival (PFS) was 6.8 months (95% confidence interval [CI]: 4.2-10.2), and the median overall survival (OS) was 10.8 months (95% CI: 7.2-16.2). No significant differences in PFS (6.8 vs. 7.9 months, P = 0.55) or OS (11.1 vs. 10.8 months, P = 0.68) were observed between patients who had received prior immunotherapy and those who had not. The most common grade 3-4 TRAEs were chemotherapy-related myelosuppression, decreased appetite, and elevated total bilirubin. One patient developed hand-foot syndrome, and another experienced immune-mediated pneumonitis. No treatment-related deaths were reported. The combination of PD-1/PD-L1 inhibitors, nab-paclitaxel, and fluorouracil-based agents (capecitabine or S-1) demonstrated manageable toxicity and modest clinical activity as a second-line therapy for advanced BTCs. This regimen may represent a feasible treatment option for patients who progress following first-line therapy. Moreover, continued administration of this immunotherapy-based combination beyond initial progression may confer survival benefits in select patients.

The Primary Health Care Corporation (PHCC) initiated a preceptorship program for undergraduate Year-2 dental students from Qatar University (QU). The study explored the placement experience of dental students and preceptors across primary PHCC health centers. An exploratory cross-sectional design was employed. The study was approved by the Department of Clinical Research in PHCC Doha, Qatar (Ref. No: BUHOOTH-D-23-00092R2BUHOOTH-D-23-00092R2). Year-2 students supervised by PHCC preceptors were included in the study. Data on the placement framework, clinical procedures, training hours, and responses to internal assessment surveys were collected from the PHCC database. Descriptive statistics were used to summarize data. Kruskal-Wallis, Bonferroni, and Mann-Whitney U tests were employed to assess the differences in categorical variables. Effect sizes were calculated using eta squared (η2) and rank‑biserial correlation (rrb) to support interpretation. The analysis was conducted at a confidence level of 95% and a significance level of 5%. The entire population of 23 students, supervised by 32 PHCC preceptors, during the 2021-2022 academic year was included. Overall, the students received consistent placement across the regions (H(2) = 4.701, p = 0.095; η2 = 0.21). Among preceptors, significant differences were observed in clinical activities (H(2) = 7.345, p = 0.025; η2 = 0.23). Post-hoc comparisons indicated elevated clinical activities in the central region compared to the western region (p = 0.023; rrb = 0.54). Education and training experience were strongly associated with higher procedural activity (U = 202.5, p = 0.004; rrb = 0.49). Overall, both students and dentists were satisfied with the placement. Notwithstanding the limitations of the study, Year-2 dental placement experiences were satisfactory. Regional service conditions rather than individual characteristics seemingly shaped clinical exposure and procedural activities. Implementing targeted adjustments, standardizing preceptors' skills, and allocating placement activities to regions with high patient turnover may help promote greater equity in training experiences and support a consistent placement model in PHCC. Not applicable.

VEXAS syndrome is characterized by high glucocorticoid (GC) requirements and frequent relapses during tapering, yet dose-response relationships remain poorly defined. We conducted a pilot study to assess the feasibility of granular longitudinal treatment-line reconstruction and to explore GC dose-response patterns associated with disease activity and flare risk. In this retrospective single-center study, we reconstructed detailed treatment trajectories of patients with VEXAS syndrome. Disease courses were segmented into treatment-line periods defined by any therapeutic modification, including GC dose changes. For each period, GC dose, concomitant therapies, and clinical activity were recorded. Associations between GC dose and disease activity were analyzed using multivariable models adjusting for concomitant treatments. Twelve patients were included, representing 315 treatment-line periods over a mean follow-up of 45months. Mean annual GC exposure was 3.27 ± 2.26g per patient. Higher GC dose (continuous variable) was independently associated with lower odds of clinical activity (aOR 0.91 per mg increase [95% CI 0.88-0.94], p < 0.001). Exploratory threshold analyses suggested increased flare risk below approximately 15mg/day (or 0.2mg/kg/day), with a lower-risk plateau above 20mg/day. The increased flare risk below 15mg/day remained significant after adjustment for concomitant therapies (HR 0.24 [95% CI 0.11-0.54], p = 0.001). Organ-specific analyses suggested heterogeneous glucocorticoid sensitivity, with higher doses appearing required for lung involvement and lower doses appearing sufficient for fever, skin, and joint manifestations. This pilot study demonstrates the feasibility of detailed treatment-line reconstruction in VEXAS syndrome and identifies GC dose-response trends. These preliminary findings provide planning parameters for a future adequately powered study aimed at validating dose thresholds and refining tapering strategies in VEXAS.

This study aimed to investigate the prognostic value of early post-induction intestinal ultrasound (IUS) findings in predicting long-term clinical outcomes among patients with moderate-to-severe ulcerative colitis (UC). This retrospective, single-center study consecutively enrolled patients with moderate-to-severe, left-sided or extensive UC. Clinical endpoints were assessed at the end of follow-up or 1 year after induction therapy (for patients with at least 1 year of follow-up) and categorized as clinical remission (Short Clinical Colitis Activity Index [SCCAI] ≤ 2) or non-remission (SCCAI > 2). Patients who experienced a negative disease course before the evaluation point were classified as clinical non-remission. A total of 56 patients were included. The bowel wall thickness (BWT; 5.1 ± 1.7 mm vs. 6.0 ±1.4 mm; P= 0.032) and Milan ultrasound criteria (MUC; 8.3 ± 3.2 vs. 9.9 ± 2.2; P= 0.029) evaluated at early follow-up IUS were lower for patients reaching longterm clinical remission. Patients with BWT < 5 mm on early follow-up IUS (83% vs. 45%; P= 0.006) or MUC < 6.2 (100% vs. 45%; P< 0.001) had a significantly higher rate of long-term clinical remission. Kaplan-Meier analysis revealed a lower cumulative probability of a negative disease course in patients with BWT < 5 mm (P= 0.025) or MUC < 6.2 (P= 0.025). Cox regression analysis identified BWT ≥ 5 mm as an independent predictor of a negative disease course. BWT <5 mm and MUC < 6.2 may serve as intermediate targets for IUS-guided "treat-to-target" strategy, offering a practical approach to improve longterm clinical remission in patients with moderate-to-severe UC.

Cereblon E3 ligase modulating drugs (CELMoDs) are next-generation immunomodulators (IMiDs) with a promising efficacy and safety profile. Early-phase clinical trials have shown clinical activity in heavily pretreated lymphomas, including those refractory to prior IMiD therapy or to cellular immunotherapies such as CAR-T. CELMoDs show potential as a fixed-duration, chemo-free option with durable responses in both relapsed/refractory (R/R) and treatment-naïve B-NHL. This review offers an exploration of cereblon (CRBN) as key for lymphomagenesis and highlights the mechanisms by which IMiDs and CELMoD target CRBN. Additionally, we discussed the key findings from early-phase clinical trials evaluating these newer agents as monotherapy and in combination regimens across first-line and R/R settings. Finally, we focused on ongoing clinical trials and discussed how CELMoDs may reshape the current treatment landscape and potentially redefine the standard of care in B-cell lymphomas.

High-risk neuroblastoma remains a challenging pediatric cancer, with survival rates lagging despite advances in multimodal therapy. This review aims to critically synthesize recent advances in GD2-directed chimeric antigen receptor (CAR) T cell therapy for neuroblastoma and to highlight its potential to improve long-term outcomes. In early-phase trials of GD2-directed CAR-T cell therapy for relapsed or refractory neuroblastoma, no dose-limiting toxicities were observed. Objective responses ranged from 6% to 33%, with durable complete remissions reported beyond 10 years. Stable disease occurred in up to 55% of patients. Cytokine release syndrome was reported in 0-90% of cases, generally mild, and neurotoxicity was rare. CAR-T cell expansion and trafficking to tumor sites have been demonstrated in several studies, although they remain variable and often limited in solid tumor settings. GD2-directed CAR-T cell therapy demonstrates limited but measurable clinical activity, particularly in minimal residual disease settings, with an overall acceptable safety profile. Continued innovation in CAR design and integration into multimodal strategies may improve long-term outcomes for this aggressive pediatric cancer.

Pharmacists play a crucial role in managing antithrombotic therapy in critically ill adults; however, data on this topic in critically ill children are limited. Therefore, we sought to characterize the types of antithrombotic therapy interventions provided by pediatric pharmacists. Via a multicenter, prospective, observational study at 9 children's hospitals in the United States, pediatric pharmacists in the pediatric intensive care unit (PICU), neonatal intensive care unit (NICU), mixed intensive care unit (ICU), and pediatric cardiac intensive care unit (PCICU) at participating centers recorded recommendations made during clinical activities during at least 20 shifts. Interventions were documented in a central REDCap database. Descriptive statistics were used to summarize the data. From July 2023 to November 2024, a total of 41 pediatric pharmacists from 9 participating institutions completed data collection on interventions during 697 shifts. A total of 12,632 accepted interventions for 2,264 patients were recorded. Among the 12,632 interventions, 1,130 (9%) were antithrombotic-related interventions, involving 693/2,264 (26.4%) patients. Most antithrombotic medication interventions occurred in the PCICU (844/1,130, 74.7%). Approximately half of the antithrombotic interventions were related to antithrombotic initiation/management (n = 607/1,130, 53.7%), with the majority involving an anticoagulant medication(s) (549/607, 90.4%). The majority of antithrombotic interventions in critically ill children were in the PCICU and involved anticoagulation for thromboembolism treatment and prevention. Further research is warranted to evaluate pediatric pharmacist-driven clinical services and the impact on antithrombotic outcomes in critically ill children, particularly those with cardiac disease.

Preliminary evidence suggests sex-related variations in clinical and serological features in idiopathic inflammatory myopathies (IIMs), yet comprehensive cohort studies, particularly within the Italian population, remain scarce. The aim of this study is to assess sex differences in clinical phenotype, serological features, and disease activity, and to identify independent associated factors of disease activity in a well-characterised multi-centre Italian IIMs cohort. A total of 228 IIMs patients from 5 tertiary Rheumatology Units across Italy were included. Demographic, clinical, serological, and treatment data were collected. Continuous variables are reported as mean ± SD or median (IQR), categorical variables as n (%). Comparisons between the 2 sexes were assessed by Student's t-test, Mann-Whitney U test, χ², or Fisher's exact test. Independent associated factors of disease activity (MYOACT) were assessed through multivariable linear regression analysis. Of 228 patients, 157 (68.9%) were female, and 71 (31.1%) were male. Age at diagnosis was similar between sexes. Males showed significantly higher disease activity measured by the MYOACT index. Multivariable analyses identified male sex, MDA5 autoantibody positivity, and greater disease damage extent as independent associated factors of higher disease activity, whereas dermatomyositis and polymyositis were associated with lower disease activity. Furthermore, MYOACT showed good predictive ability to define patients at risk for intensive care unit admission with an optimal threshold of 0.23. These findings highlight relevant sex-related differences in clinical expression and may support more personalised management strategies.

Randomised controlled trials (RCTs) use restrictive eligibility criteria, raising concerns about external validity for heterogeneous routine-care populations. We aimed to characterise real-world patients with rheumatoid arthritis who would be ineligible for phase III RCTs, to evaluate their outcomes on biological/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in routine care and to assess how eligibility status influences comparative effectiveness estimates. We analysed 5462 patients who initiated b/tsDMARDs between 2003 and 2023. RCT ineligibility was defined using common phase III trial exclusions (eg, renal/hepatic impairment). Outcomes were treatment persistence and Clinical Disease Activity Index remission at 26 weeks. Comparative effectiveness across drug classes was estimated using propensity score weighting, stratified by RCT eligibility. Overall, 39.7% (2167/5462) met at least one RCT exclusion criterion and ineligible patients had higher baseline disease activity and worse functional status. However, after propensity score adjustment for clinical characteristics, remission rates did not differ between groups (24.0% vs 23.2%; OR 0.90; 95% CI 0.78 to 1.04). The proportion ineligible differed by b/tsDMARDs, highest with interleukin 6 inhibitors (47.4%) and CTLA4-Ig (45.1%) and lowest with Janus kinase (JAK) inhibitors (31.0%). In the RCT-eligible cohort, remission with JAK inhibitors exceeded that with tumour necrosis factor inhibitors (OR 1.39; 95% CI 1.09 to 1.76), consistent with head-to-head RCTs. In the RCT-ineligible cohort, this advantage was attenuated and no longer statistically significant (OR 1.24; 95% CI 0.81 to 1.91). Approximately 40% of routine-care patients would be RCT ineligible. Although these patients achieved comparable adjusted outcomes, between-drug differences were smaller than in trial-eligible populations. Real-world comparative analysis should therefore consider composition and calendar time when interpreting treatment effects.

Mitoxantrone hydrochloride liposome (Lipo-MIT), an innovative anthracycline nano-drug, has demonstrated a favorable pharmacokinetics (PK) profile in lymphoma and preliminary efficacy in adult acute myeloid leukemia (AML). This study investigated the PK profile, efficacy, and safety of Lipo-MIT plus cytarabine in newly diagnosed pediatric AML. In this single-arm, open-label trial, eligible patients received Lipo-MIT and cytarabine every 4weeks for two cycles. The primary endpoint was the PK characteristics of Lipo-MIT after the first dose. Between July 19, 2023, and November 14, 2023, eight pediatric patients were enrolled. The total and free mitoxantrone concentrations increased rapidly during the absorption phase and then declined gradually to minimal concentrations before the administration of the second dose. The mean elimination half-life of total mitoxantrone was 60.2 ± 9.4h, and the ratio of the area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration (AUC0- t) of free mitoxantrone to total mitoxantrone was 1.8% ± 0.6%. The overall response rate and composite complete remission rate were both 85.7% (6/7). Measurable residual disease negativity was achieved in four (66.7%) patients after Cycle 1 and in six (100.0%) after Cycle 2. The 1-year relapse-free survival rate was 83.3%. The common Grade ≥3 treatment-related adverse events were hematological toxicities (100.0%) and soft tissue infection (28.6%). No treatment-related deaths occurred. Lipo-MIT plus cytarabine showed a favorable PK profile and a manageable safety profile in newly diagnosed pediatric AML, with early evidence of clinical activity in this population. Chinese Clinical Trial Registry: ChiCTR2300067964 (https://www.chictr.org.cn/showproj.html?proj=188738).

BackgroundRelapsed or refractory (R/R) B-cell non-Hodgkin’s lymphoma (B-NHL) remains a major therapeutic challenge despite CD19-directed chimeric antigen receptor (CAR) T-cell therapies, with treatment failure often driven by antigen escape and limited CAR-T persistence. Dual targeting of CD19 and CD20 may mitigate antigen loss. We conducted an expanded phase I/II study of bispecific CD19/20 CAR-T cells and incorporated spatially resolved single-cell transcriptomics to evaluate tumor-intrinsic and microenvironmental factors of clinical response.MethodsPatients with R/R B-NHL received CD19/20 CAR-T cells following lymphodepletion. Efficacy, safety, CAR-T expansion/persistence, and B-cell reconstitution were assessed. Pretreatment tumor biopsies from five patients with divergent outcomes underwent spatial single-cell transcriptomic profiling.Results32 patients were treated, including 24 with diffuse large B-cell lymphoma. Among 31 evaluable patients, the best overall response rate was 74%, including 58% achieving complete remission. Median progression-free and overall survival were 6.8 and 22.1 months, respectively. Response rates were higher in patients with normal lactate dehydrogenase. CAR-T expansion peaked on days 7–17, and persistence exceeded 500 days in long-term responders. Cytokine release syndrome occurred in 53% (12% grade ≥3) and immune effector cell-associated neurotoxicity syndrome in 9% (all grade 3), with no lasting deficits. Spatial profiling identified two dominant tumor architectures: (1) a B-cell-dominant phenotype, in which durable remission was associated with heightened apoptotic competence in malignant B cells, and (2) a fibroblast-enriched and monocyte/macrophage-enriched phenotype, in which response correlated with a chemokine-rich, T-cell-permissive microenvironment.ConclusionsBispecific CD19/20 CAR-T therapy produced durable clinical activity with manageable toxicity. Spatial single-cell analysis reveals distinct tumor-intrinsic and microenvironmental features associated with CAR-T responsiveness, providing a spatially informed framework for understanding heterogeneous therapeutic outcomes.Trial registration numberNCT04723914.

Multi-pinhole cardiac-dedicated CZT gamma cameras improve clinical workflow by reducing acquisition duration and/or injected activities. As most of these systems lack integrated CT scanner, attenuation artifacts may appear in the reconstructed image depending on patient morphology. External CT-based attenuation correction is possible but requires manual SPECT-CT registration and increases patient absorbed dose. The aim of the present study was to develop an approach to estimate patient-specific attenuation maps directly from emission data acquired on a pinhole cardiac CZT camera. Two anthropomorphic torso phantoms were used. Their heart wall (with or without defects), liver insert and background cavity were filled with 99mTc solutions to simulate clinical activities. Reference acquisitions were obtained using a CZT SPECT/CT system. For each phantom, two acquisitions were performed on a pinhole cardiac CZT camera: a standard cardiac acquisition and a second acquisition with detectors radially moved away. Combination of both acquisitions enabled delineation of the body contour and segmentation of soft-tissue and lung regions. From this segmentation, a CT-free attenuation map was generated and imported into the manufacturer's reconstruction software to produce attenuation corrected (AC) images. These CT-free AC images were semi-quantitatively compared, using 17-segment polar maps, to (1) images corrected using a registered external CT, (2) AC images from the CZT SPECT/CT system, and (3) the true activity distribution in the phantoms. A three-dimensional voxel-wise comparison was also performed between CT-free AC and CT-based AC images of the pinhole CZT camera. CT-free attenuation maps produced tracer distribution and 17-segment polar maps closely matching those obtained with CT-based attenuation correction. Heart wall defects in the anterior and inferior areas remained clearly visible except for half-obstructive defects. Differences relative to CZT SPECT/CT images were mainly attributable to camera geometry and reconstruction algorithm. The novel CT-free patient-specific attenuation correction method yields images comparable to CT-based AC images and shows good agreement with AC images from a CZT SPECT/CT system. This approach could enhance the diagnostic performance of current cardiac pinhole CZT cameras without requiring additional CT acquisitions.

Mycophenolate mofetil (MMF) is widely used in lupus nephritis (LN), but interindividual variability in pharmacokinetics and pharmacogenetics may affect treatment response. This study investigated the relationship between MMF pharmacokinetics, key genetic polymorphisms, and therapeutic response in Egyptian female LN patients. In this prospective study, 53 female patients with active LN (ISN/RPS class III-IV) maintained on 2g/day MMF were enrolled at the Urology and Nephrology Center, Mansoura University, Egypt. Baseline clinical, laboratory, and histopathological data were collected. Serial blood samples were obtained over 8h for mycophenolic acid (MPA) quantification by LC/MS. Genomic DNA was extracted for UGT2B7 (rs7438135) and SLCO1B1 (rs183624077) genotyping using TaqMan real-time PCR assays. Treatment response was classified as complete or partial remission versus non-response at 6 months. Population pharmacokinetics were analyzed using Monolix 2020R1. Considerable variability in MPA exposure was observed (mean AUC₀-₈: 22.4 ± 12.9µg·h/mL; mean Cmax: 12.9 ± 5.5µg/mL). Responders exhibited higher median AUC₀-₈ than non-responders (23.1 vs. 16.2µg·h/mL; p = 0.039). SLCO1B1 and UGT2B7 genotypes did not differ significantly between responders and non-responders, though TT carriers showed lower MPA AUC₀-₈. Multivariate analysis identified biopsy class (III vs. IV), induction therapy with MMF, and higher MPA AUC₀-₈ as independent predictors of response. MMF exposure, biopsy class, and induction regimen significantly influence therapeutic response in LN. Pharmacokinetic monitoring of MPA may help optimize MMF therapy, while common UGT2B7 and SLCO1B1 variants showed limited predictive value in this cohort.

Tongue coating, severity of Ama, and disease activity in patients with Rheumatoid Arthritis: A pilot study.