Nevin Manimala

Adv Ther. 2025 Jul 4. doi: 10.1007/s12325-025-03278-5. Online ahead of print.

ABSTRACT

INTRODUCTION: The phase 3 CARTITUDE-4 trial demonstrated superiority of ciltacabtagene autoleucel (cilta-cel) over daratumumab, pomalidomide and dexamethasone, or pomalidomide, bortezomib and dexamethasone, in lenalidomide-refractory patients with relapsed/refractory multiple myeloma (RRMM) who received 1-3 prior lines of therapy. The comparative efficacy of cilta-cel was previously evaluated against other common regimens. Here, we present an updated comparative efficacy assessment, including OS, between cilta-cel (CARTITUDE-4 34-month median follow-up) and common regimens.

METHODS: Individual patient data were available from CARTITUDE-4 (cilta-cel), CASTOR (daratumumab, bortezomib and dexamethasone [DVd]), CANDOR (daratumumab, carfilzomib and dexamethasone [DKd] and carfilzomib and dexamethasone [Kd]) and APOLLO (pomalidomide and dexamethasone [Pd]). Inverse probability of treatment weighting (IPTW) was used to adjust for key baseline patient characteristic imbalances. Relative efficacies were estimated with response rate ratios and 95% confidence intervals (CIs) for response rates, with hazard ratios (HRs) and 95% CIs for PFS and OS. Sensitivity analyses using alternative statistical approaches were explored.

RESULTS: After excluding 53 patients with prior anti-CD38 therapy exposure, cilta-cel (n = 155) was compared with DVd (n = 44), DKd (n = 98), Kd (n = 46) and Pd (n = 92). Baseline covariates were generally well balanced across cohorts after IPTW. Cilta-cel showed significant improvements in PFS (HR 0.21-0.58; p ≤ 0.01) and OS (HR 0.31-0.55; p < 0.05) vs all regimens. With longer follow-up, the relative benefit of cilta-cel versus other regimens further increased on deeper levels of response. Although all results, except ORR, significantly favored cilta-cel, the DKd comparison provided the most conservative estimates.

CONCLUSION: This updated analysis confirms previously observed significant superiority of PFS and response outcomes of cilta-cel while showing significant OS benefit compared with common regimens for this population. These findings support cilta-cel as an effective treatment for lenalidomide-refractory RRMM patients as early as second line.

TRIAL REGISTRATION: CARTITUDE-4 ClinicalTrials.gov ID: NCT04181827.

PMID:40613875 | DOI:10.1007/s12325-025-03278-5

Ear Nose Throat J. 2025 Jul 4:1455613251356359. doi: 10.1177/01455613251356359. Online ahead of print.

ABSTRACT

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with polyps, and sensitivity to aspirin (ASA). Optimal treatment requires coordinated medical and surgical management, with prior studies showing that a single-center approach to AERD management yields improved sinonasal patient outcomes. Here, we sought to evaluate whether institutional experience enhances pulmonary and sinonasal outcomes in patients with AERD undergoing functional endoscopic sinus surgery (FESS) followed by ASA desensitization (AD).

METHODS: Single-center, retrospective cohort study evaluating patients undergoing FESS and AD from 2016 to 2024. Cohorts were defined as “early” (2016-2019) and “late” (2020-2024). Demographics, clinical history, and quality of life metrics [eg, 22-Item SinoNasal Outcome Test (SNOT-22) score] were assessed. Cohorts were compared with statistical significance defined as P < .05.

RESULTS: Two hundred sixty-two patients (n = 145 early, 117 late) met inclusion criteria. The late cohort was younger (mean 49.6 vs 56.4 years, P = .042) with fewer prior surgeries (1.33 vs 2.64, P ≤ .001) at the time of referral. Results showed a reduced need for inhaled corticosteroids and beta-agonists in the late cohort and improved SNOT-22 rhinologic sub-scores in the early post-treatment period (post-FESS, pre-AD; 2-3 months post-treatment; 4-6 months post-treatment), with a reduced need for revision surgery (0% vs 6.9%, P = .010).

CONCLUSIONS: Greater institutional experience in AERD management yields significantly improved pulmonary outcomes and more rapid improvement in sinonasal outcomes. This was felt to be due to enhanced communication and coordination of care between the allergist and rhinologist, with implications for healthcare expenditures.

PMID:40613262 | DOI:10.1177/01455613251356359

Am J Hematol. 2025 Jul 4. doi: 10.1002/ajh.27762. Online ahead of print.

ABSTRACT

Nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) may be an antigen-driven malignancy. Recent studies demonstrated that in NLPHL patients, lymphoma B-cell receptor can bind proteins derived from Moraxella catarrhalis (MC) and Rothia mucilaginosa (RM). We examined whether MC and RM can be detected in NLPHL lymph nodes. The presence of MC DNA and RNA was tested by polymerase chain reaction (PCR) and RNAScope in situ hybridization (ISH), respectively. The presence of RM DNA was tested by PCR. We demonstrated the presence of MC DNA in 29 of 49 (59.2%) NLPHL patient tumor samples and RNA in 14 of 39 biopsies (35.9%), with good concordance between the assays, considering lower RNA stability in older biopsies and lower sensitivity of ISH compared to PCR. In comparison, 36 lymph nodes with follicular hyperplasia and a specimen with tubular adenoma were negative for MC by PCR, and only 6 of 37 non-NLPHL lymphoma tissues (16.2%) were positive for detection of MC by PCR, demonstrating a statistically higher detection rate of MC in patients with NLPHL (p = 0.00006). MC was detected in NLPHL samples at diagnosis and relapses, and there was no statistical difference in the detection rate for MC between IgD positive and negative samples. In contrast, RM was detected by PCR in 9 of 49 (18.4%) NLPHL patient tumor samples, always concomitantly with MC without statistical difference in comparison to other lymphomas. The high prevalence of MC in NLPHL tumor tissues provides direct evidence for its association with NLPHL.

PMID:40613259 | DOI:10.1002/ajh.27762

Oral Health Prev Dent. 2025 Jul 4;23:355-364. doi: 10.3290/j.ohpd.c_2117.

ABSTRACT

PURPOSE: To evaluate surface roughness and volumetric change of enamel after using different resin remnant removal (RRR) techniques, following orthodontic bracket debonding.

MATERIALS AND METHODS: Metal orthodontic brackets (Mini Twin Brackets, RMO) were bonded to 60 human (central or lateral) labial mid-third surfaces, and debonded 24 h after by a single orthodontist. The remaining composites were completely removed with the fluorescence light guidance by the D-Light-Pro led curing unit (GC/detection mode). The removal procedures were performed without magnification (n = 30) or with 20× magnification/5500 K illumination by a dental microscope (OMS2000, Zumax) (n = 30). Three RRR techniques were used: 12-bladed carbide bur (Horico), red-banded diamond bur (Horico), SofLex Disc (medium/40 μm, fine/24 μm, and superfine/8 µm; 3M). Surface changes were evaluated visually through microscope photographs by enamel surface index (ESI) and volumetrically by overlapping the three-dimensional images of a laser scanner device (LAS-20, SD-Mechatronik) in the Geomagic Design X (3D Systems) software. The deemed significance was set at 0.050 for the statistical analyses.

RESULTS: A positive, strong correlation was found between visual and volumetric change scores (P 0.001). Lesser volumetric loss (P 0.001) and roughness (P = 0.009) were observed for all RRR techniques when the magnification was used. Volumetric loss (mm3) by diamond bur was significantly the highest [1.85(1-3)a], followed by SofLex Disc [1.1(1-1)c] and carbide bur [0.59(0-1)b](P 0.001). Visual surface roughness scores (Ra) were significantly higher for diamond bur [4.5(4-5)b](P 0.001), followed by carbide bur 2(1-3)a and SofLex Disc 1(1-2)a.

CONCLUSION: Surface roughness should always be assessed together with the volumetric enamel loss for the selection of RRR technique. Red-banded diamond bur should not be used for RRR. Even though the least surface roughness can be provided by SofLex Disc system, it can provide more intact enamel surface loss than the carbide bur. Magnification was considered useful for the RRR to provide a smoother surface while better preserving the intact enamel tissue.

PMID:40613251 | DOI:10.3290/j.ohpd.c_2117

Clin Trials. 2025 Jul 4:17407745251344524. doi: 10.1177/17407745251344524. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Existing regulatory and ethical guidance does not address real-life complexities in how clinical trial participants’ level of participation may change. If these complexities are inappropriately managed, there may be negative consequences for trial participants and the integrity of trials they participate in. These concerns have been highlighted over many years, but there remains no single, comprehensive guidance for managing participation changes in ways that address real-life complexities while maximally promoting participant interests and trial integrity. Motivated by the lack of agreed standards, and observed variability in practice, representatives from academic clinical trials units and linked organisations in the United Kingdom initiated the PeRSEVERE project (PRincipleS for handling end-of-participation EVEnts in clinical trials REsearch) to agree on guiding principles and explore how these principles should be implemented.

METHODS: We developed the PeRSEVERE principles through discussion and debate within a large, multidisciplinary collaboration, including research professionals and public contributors. We took an inclusive approach to drafting the principles, incorporating new ideas if they were within project scope. Our draft principles were scrutinised through an international consultation survey which focussed on the principles’ clarity, feasibility, novelty and acceptability. Survey responses were analysed descriptively (for category questions) and using a combination of deductive and inductive analysis (for open questions). We used predefined rules to guide feedback handling. After finalising the principles, we developed accompanying implementation guidance from several sources.

RESULTS: In total, 280 people from 9 countries took part in the consultation survey. Feedback showed strong support for the principles with 96% of respondents agreeing with the principles’ key messages. Based on our predefined rules, it was not necessary to amend our draft principles, but comments were nonetheless used to enhance the final project outputs. Our 17 finalised principles comprise 7 fundamental, ‘overarching’ principles, 6 about trial design and setup, 2 covering data collection and monitoring, and 2 on trial analysis and reporting.

CONCLUSION: We devised a comprehensive set of guiding principles, with detailed practical recommendations, to aid the management of clinical trial participation changes, building on existing ethical and regulatory texts. Our outputs reflect the contributions of a substantial number of individuals, including public contributors and research professionals with various specialisms. This lends weight to our recommendations, which have implications for everyone who designs, funds, conducts, oversees or participates in trials. We suggest our principles could lead to improved standards in clinical trials and better experiences for participants. We encourage others to build on our work to explore the application of these ideas in other settings and to generate empirical evidence to support best practice in this area.

PMID:40613224 | DOI:10.1177/17407745251344524

Front Biosci (Schol Ed). 2025 Jun 25;17(2):38388. doi: 10.31083/FBS38388.

ABSTRACT

BACKGROUND: While an increase in fetal hemoglobin (HbF) has no consequences in healthy adults, clinical benefits can be promoted in sickle cell disease (SCD) and β-thalassemia patients. Single-nucleotide polymorphisms (SNPs) in three genomic regions: the HBB gene cluster, the BCL11A gene, and the HBS1L-MYB (HMIP) intergenic region, have been associated with HbF regulation. Therefore, the present study aimed to examine the potential association of SNPs in BCL11A (rs11886868 and rs1427407), HMIP (rs66650371 and rs4895441), HBG2 (rs7482144), and BGLT3 (rs7924684) with HbF levels in an adult population sample from São Tomé e Príncipe (Central Africa).

METHODS: A total of 145 women aged 18 to 49 years were involved in this study, comprising 98 women with the normal hemoglobin (Hb) genotype (HbAA) and 47 with sickle cell trait (HbAS). From the HbAA individuals, we selected a control group of 60 subjects with normal HbF levels, ranging from 0.2% to 1.4% (mean: 0.75%), and a case group of 38 subjects with elevated HbF levels, ranging from 1.8% to 3.7% (mean: 2.35%). In the group of HbAS individuals, the HbF levels ranged from 0.4% to 3.7% (mean: 1.56%). SNP genotyping was conducted using standard molecular methods.

RESULTS: Logistic regression, in the additive model, revealed significant associations with increased levels of HbF for the minor alleles of the two BCL11A SNPs, rs11886868 [C] and rs1427407 [T], in HbAA women (p = 0.00018 and p = 0.00076, respectively). When comparisons of HbF levels were conducted among genotypes in the HbAA women, significant differences were observed for BCL11A SNPs rs11886868 and rs1427407, as well as for the HBG2 rs7482144 and BGLT3 rs7924684 variants. We found no association between HbF levels and the two HMIP variants rs66650371 and rs4895441 in the HbAA women. Among the HbAS women, no statistically significant associations were observed between the six analyzed polymorphisms and HbF levels (p > 0.05).

CONCLUSIONS: We successfully replicated the association between the two well-known BCL11A SNPs, rs11886868 and rs1427407, with HbF levels in women with the normal HbAA genotype from São Tomé e Príncipe. Other signals of association with HbF levels were identified for the SNPs HBG2 (rs7482144) and BGLT3 (rs7924684).

PMID:40613211 | DOI:10.31083/FBS38388

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):881-885. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.039.

ABSTRACT

OBJECTIVE: To analyze the laboratory detection results of hemolytic disease of the fetus and newborn(HDFN).

METHODS: Related test results of 283 newborns and their mothers’ blood samples from Kunming Maternal and Child Health Hospital from August 2023 to May 2024 were collected, including mother and child ABO blood group, RhD blood group, as well as 3 tests of HDFN, total bilirubin (TBil) and indirect bilirubin (IBil).

RESULTS: 283 were ABO incompatibility, among which 187 were HDFN positive, with a positive rate of 66.08%; the positive rate of HDFN in neonates with antigen-A incompatibility was 74.12%(126/170), the positive rate of HDFN in neonates with antigen-B incompatibility was 53.57%(60/112), which was the highest in neonates with O/A incompatibility ［75.45%(126/167)］, followed by O/B incompatibility［54.55%(60/110)］. Group by age, the positive rates of HDFN in the ≤1 d group, 2 d group, 3 d group, 4 d group, 5 d group and ≥6 d group were 76.03%(111/146), 67.86%(38/56), 57.14%(24/42), 38.46%(5/13), 46.15%(6/13) and 23.08%(3/13), respectively. With the increase of age, the positive rates of HDFN gradually decreased, there was a statistically significant difference between the ≤3 day age group and >3 day age group ( P <0.05). There was no statistically significant difference in TBil and IBil levels between the “direct antibody+indirect antibody+release+” group and the HDFN negative group in newborns. HDFN infants exhibited a rapid increase in bilirubin levels within the first day after birth, with significantly higher TBil and IBil values compared to Non ABO-HDFN infants in the ≤1 day group ( P <0.01). However, the difference of bilirubin levels between the two groups gradually narrowed from 2-6 days after birth, and the difference was not statistically significant (P >0.05). The peak value of TBil and IBil occurred on the 4th day after birth in HDFN infants.

CONCLUSION: ABO-HDFN is most commonly seen in newborns whose mothers are type-O, and the positive rate was the highest in newborns with O/A incompatibility. The detection rate of HDFN is affected by the age of the newborns, and the two were correlated inversely. ABO-HDFN group developed more rapidly with a higher peak. Therefore, HDFN tests should be carried out as soon as possible for mothers and newborns with incompatible blood types, and appropriate treatment should be provided to prevent complications.

PMID:40613186 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.039

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):875-880. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.038.

ABSTRACT

OBJECTIVE: To investigate the pattern of hepatitis B virus (HBV) infection and the prevalence of hepatitis D virus (HDV) infection among voluntary blood donors who tested reactive for HBV in Wuhan, and to provide data support for the prevention and treatment of HBV and HDV infections.

METHODS: Electrochemiluminescence (ECL) method was used to detect hepatitis B serological markers in the samples with HBsAg and/or HBV DNA reactivity, and the HBV infection in different groups was statistically analyzed. The HDV IgM and IgG antibodies were screened by ELISA, and the prevalence of HDV infection in the retained samples was analyzed.

RESULTS: In 351 ELISA and/or nucleic acid test (NAT) reactive samples, the serological tests for hepatitis B revealed that 4 cases (1.1%) were positive for HBsAg, HBeAg, and anti-HBc, 182 cases (51.9%) were positive for HBsAg, anti-HBe, and anti-HBc, and 55 cases (15.7%) were negative for HBsAg but positive for anti-HBc. Among them, the HBsAg ELISA dual reagent reactive group (HBsAg R&R group) and the HBsAg ELISA single reagent reactive/HBV DNA reactive group (HBsAg R&NR/HBV DNA R group) had the highest rates of HBsAg(+), anti-HBe(+), and anti-HBc(+), accounting for more than 90% and 65%, respectively, followed by low activity of HBV acute infection or chronic carriers, accounting for about 5% and 20%, respectively. In the HBsAg R&NR/HBV DNA NR group, the combined proportion of individuals with anti-HBs single positive and all hepatitis B serological markers negative accounted for 78%, and those who were HBsAg negative but anti-HBc positive accounted for approximately 20%. In the HBsAg NR&NR/HBV DNA R group, there was nearly 9% of HBsAg(+), anti-HBe(+), and anti-HBc(+), the remaining were all HBsAg negative but anti-HBc positive, with a 100% anti-HBc positivity rate in this group. No HDV IgM or IgG antibodies were detected in the retained samples.

CONCLUSION: Blood donors with HBV-reactive results in blood screening exhibit multiple patterns of infection indicators. The prevalence rate of HDV infection among blood donors in Wuhan is extremely low. However, the risk of asymptomatic occult hepatitis B infection (OBI) blood donors being co-infected with HDV should not be overlooked in areas with high prevalence of HBV.

PMID:40613185 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.038

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):848-852. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.033.

ABSTRACT

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia.

METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups.

RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups.

CONCLUSION: The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.

PMID:40613180 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.033

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):841-847. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.032.

ABSTRACT

OBJECTIVE: To investigate the relationship between peripheral blood T-cell immunoglobulin mucin-3 (TIM-3) and iron overload in patients with myelodysplastic syndrome (MDS) undergoing red blood cell transfusion.

METHODS: 120 MDS patients who received treatment at Wuhan Third Hospital from June 2020 to May 2022 were included and analyzed as research subjects, all of whom met the indications for red blood cell transfusion. Blood routine and biochemical indicators were tested before transfusion, and general clinical data of the patients were statistically analyzed. The iron metabolism status of the patients were evaluated. The clinical characteristics of patients with iron overload and the factors affecting iron overload were analyzed. And a correlation analysis was conducted between TIM-3 and other factors affecting iron overload.

RESULTS: Among the 120 MDS patients included in this study, 82 cases (68.33%) were detected to have iron overload after red blood cell transfusion. The occurrence time of iron overload was 20-42 weeks, with an average time of 32.35±5.26 weeks, calculated from the first transfusion of red blood cells. The proportion of patients with high-risk and extremely high-risk according to the revised International Prognostic Scoring System (IPSS-R) and WHO classification-based Prognostic Scoring System (WPSS), the volume of blood transfusions, the proportion of transfusion-dependent patients, and the levels of serum hepcidin (Hepc), erythropoietin (EPO), and TIM-3 in patients with iron overload were higher than those in patients with normal iron metabolism, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that high-risk and extremely high-risk according to WPSS, blood transfusion volume, transfusion dependence, and upregulation of serum Hepc, EPO, and TIM-3 expression were factors affecting iron overload in MDS patients undergoing red blood cell transfusion (P < 0.05). Pearson correlation analysis showed that serum TIM-3 level in MDS patients were positively correlated with the other factors affecting iron overload (P < 0.05).

CONCLUSION: Serum TIM-3 is associated with iron overload in MDS patients undergoing red blood cell transfusion, and upregulation of serum TIM-3 expression increases the risk of iron overload after red blood cell transfusion.

PMID:40613179 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.032