Tag: nevin manimala

Clin Rheumatol. 2025 Jul 4. doi: 10.1007/s10067-025-07483-z. Online ahead of print.

ABSTRACT

BACKGROUNDS: Lupus nephritis (LN) is a major cause of morbidity among patients with systemic lupus erythematosus (SLE). Unfortunately, some patients do not respond adequately to available therapies, and the gene expression changes underlying this refractory state are still poorly understood. Therefore, it is crucial to gain a better understanding of the molecular mechanisms involved in refractory LN.

METHODS: Integrated proteomic and transcriptomic analysis was conducted to characterize the unique gene expression profiles in patients with refractory LN. DEGs/DAPs were identified based on the concordance between transcriptome and proteome data. Subsequently, functional enrichment analyses and protein-protein interaction network analyses were performed. Module analysis was carried out using the Search Tool for the Retrieval of Interacting Genes and Cytoscape software. Additionally, the clinical features of these patients were explored. To identify potential therapeutic agents, the Connectivity Map L1000 platform was employed.

RESULTS: Seventeen patients were included in the study, 12 non-refractory LN and 5 refractory LN. There was no statistically significant difference in demographic data, clinical characteristics and laboratory findings. There were 1019 DAPs in non-refractory LN compared with refractory LN and 47 DEGs totally in glomeruli and tubulointerstitium from GSE200306 dataset between two groups. Finally, we obtained 7 DEGs/DAPs, including CD59, JAK1, VCAM1, C8A, PIGR, TGFBI and VTN. The functions and pathways associated with the DEGs/DAPs mainly associated with complement and coagulation cascades. We also found that T cells CD4 memory (activated) downregulated in refractory LN. In both proteomics and transcriptomics analysis, CD59 was downregulated in refractory LN. And CD59 positively correlated with Alb and negatively correlated with CH50. In addition, we discovered several chemicals as potential treatment options for refractory LN.

CONCLUSIONS: According to our research findings, we have discovered that abnormal activation and functional defects of the complement system play a significant role in refractory lupus nephritis. In particular, the decreased expression of CD59 indicates abnormal complement activation. Therefore, inhibiting complement activation may become a new strategy for treating refractory LN. Key Points • The first explore of specific gene expression changes associated with refractory LN combined transcriptomics and proteomics analysis. • The functions and pathways associated with the DEGs/DAPs mainly associated with complement and coagulation cascades. • CD59 was downregulated in refractory LN. CD59 positively correlated with Alb and negatively correlated with CH50.

PMID:40613967 | DOI:10.1007/s10067-025-07483-z

Int Ophthalmol. 2025 Jul 4;45(1):276. doi: 10.1007/s10792-025-03641-z.

ABSTRACT

OBJECTIVE: To use a literature review methodology to assess the efficacy of three distinct approaches: enucleation, radiotherapy or radiotherapy prior to enucleation, in reducing patient mortality.

METHODS: Computers were used to search databases such as PubMed, Web of Science, Embase, Cochrane Library, and CNKI, as well as the references of pertinent literature. Data were extracted from the included research literature according to the pre-defined data extraction table, encompassing study characteristics, sample size, interventions, outcome measures, etc. The Cochrane risk of bias evaluation instrument was employed to assess the excellence of encompassed researches, and the RevMan software was utilized for conducting the meta-analysis.

RESULTS: 10 final articles were included, with 3 studies among them presenting the overall mortality rate at five-year follow-up. The homogeneity trial (P = 0.02, I² = 75%) showed remarkable heterogeneity, leading to the adoption of a random-effects model. The meta-analysis findings unveiled a distinction in the total mortality rate between the two groups (RR = 0.98, 95%CI was 0.81 ~ 1.18, P < 0.01). Five of the included studies reported mortality due to tumor metastasis during five-year follow-up. The homogeneity test (P = 0.03, I² = 64%) showed the presence of heterogeneity, leading to the utilization of a random effects model. The meta-analysis results revealed a remarkable disparity in mortality due to tumor metastasis between the two groups (RR = 0.88, 95%CI was 0.70 ~ 1.10, P < 0.01). Five of the included studies reported total mortality during a ten-year follow-up period. The homogeneity test (P = 0.99, I ² = 0%) demonstrated no heterogeneity, necessitating the adoption of a fixed model. The meta-analysis revealed no statistically significant difference in total mortality between the two groups (RR = 1.04, 95%CI = 0.92-1.17, P = 0.55). Four of the included studies reported mortality due to tumor metastasis at ten-year follow-up. The homogeneity trial (P = 0.41, I² = 0%) showed the absence of heterogeneity, prompting the application of a fixed effects model. The meta-analysis demonstrated no statistically significant difference in mortality due to tumor metastasis between the two groups (RR = 0.84, 95%CI = 0.67-1.05, P = 0.12).

CONCLUSION: There are disparities in the five-year overall mortality and mortality caused by tumor metastasis between enucleation and radiotherapy for CM. When selecting clinical treatment options, the patient’s condition, age, physical condition and personal preferences should be comprehensively taken into consideration, along with other factors, to determine the most appropriate treatment strategy.

PMID:40613960 | DOI:10.1007/s10792-025-03641-z

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 4. doi: 10.1007/s00210-025-04408-0. Online ahead of print.

ABSTRACT

Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, is an aggressive subtype with limited treatment options, underscoring the need for novel therapeutic strategies. This study presents the development of chondroitin sulfate-conjugated, octadecylamine-modified PLGA lipid-polymer hybrid nanoparticles (CS-SAL-LPNPs) for targeted delivery of salinomycin (SAL), a Wnt/β-catenin pathway inhibitor, to sensitize TNBC cells to apoptosis induced by TRAIL through targeted CD44 receptor-mediated uptake. Successful nanoparticle conjugation was confirmed using FTIR and NMR spectroscopy, yielding nanoparticles of 172.36 ± 5.24 nm with a zeta potential of – 26.84 ± 0.25 mV, optimal for cellular uptake and stability. The cellular uptake of CS-SAL-LPNPs was significantly enhanced, as confirmed by confocal microscopy and flow cytometry, showing a statistically significant (p < 0.05; n ≥ 3) 1.45-fold higher fluorescence intensity compared to non-targeted systems. CS-SAL-LPNPs exhibited potent cytotoxicity, with a IC₅₀ of 3.5 µM, and effectively modulated apoptosis-related protein expression by downregulating anti-apoptotic proteins such as Bcl-2 and survivin while upregulating the pro-apoptotic protein caspase-3. These changes indicate disruption of the Wnt/β-catenin signaling pathway, enhancing TRAIL-mediated apoptosis in TNBC cells. These findings demonstrate promising in vitro therapeutic efficacy of CS-SAL-LPNPs, warranting further preclinical in vivo studies for comprehensive validation.

PMID:40613939 | DOI:10.1007/s00210-025-04408-0

Langenbecks Arch Surg. 2025 Jul 4;410(1):214. doi: 10.1007/s00423-025-03756-y.

ABSTRACT

BACKGROUND: Hepaticojejunostomy (HJ) is a crucial reconstructive step in upper gastrointestinal (UGI), pancreaticoduodenectomy (PD), and Hepaticobiliarypancreatic (HBP) surgeries. The optimal suturing technique remains debated, with conflicting evidence regarding operative efficiency, costs, and complications. This meta-analysis compares continuous and interrupted suturing to provide evidence-based recommendations.

METHODS: A systematic review and meta-analysis were conducted using PubMed, Embase, and Cochrane Library. Primary outcomes were anastomotic time and costs, while secondary outcomes included bile leakage, anastomotic stricture, morbidity, cholangitis, hospital stay, and re-exploration rates. A random or fixed-effects model was applied based on heterogeneity. We included randomized controlled trials and non-randomized cohort studies. The risk of bias was assessed using the Cochrane ROB 2 tool, Newcastle-Ottawa Scale (NOS), and MINORS instrument as appropriate. Additionally, the quality of evidence for each outcome was evaluated using the GRADE approach. Sensitivity analyses were performed using the leave-one-out method.

RESULTS: Seven studies (1,159 patients) were included (continuous: 388, interrupted: 771). Continuous suturing significantly reduced anastomotic time (MD = -13.06 min, 95% CI: -17.37 to -8.75, P < 0.001) and costs (SMD = -4.89, 95% CI: -6.10 to -3.67, P < 0.001). However, no significant differences were observed in bile leakage, anastomotic stricture, morbidity, cholangitis, hospital stay, or re-exploration rates (P > 0.05). Sensitivity analyses confirmed these findings.

CONCLUSION: Continuous suturing reduces anastomotic time by ~ 13 min and costs by ~ $90 without increasing complications. While these differences may be statistically significant, their clinical relevance can vary depending on the surgical context. Surgical choice should consider surgeon expertise, institutional protocols, and patient factors. Further randomized controlled trials are necessary to validate these findings.

PMID:40613910 | DOI:10.1007/s00423-025-03756-y

Skeletal Radiol. 2025 Jul 4. doi: 10.1007/s00256-025-04961-y. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of a dynamic ultrasound-based diagnostic protocol designed to improve the diagnosis of slipping rib syndrome in the largest cohort of pediatric patients to date.

MATERIALS AND METHODS: A retrospective chart review was conducted for patients who presented to Phoenix Children’s Hospital with suspected slipping rib syndrome who underwent dynamic ultrasound-based evaluation from March of 2017 to May of 2022. A focused history and detailed imaging were performed, and dynamic ultrasound exam was conducted and compared with surgical and physical exam findings from pediatric surgeons specializing in slipping rib syndrome. Statistical analyses were performed.

RESULTS: Two hundred twenty-seven patients were evaluated for slipping rib syndrome during the study period, resulting in 301 ultrasound evaluations, with 78% of patients undergoing a single evaluation and 22% undergoing multiple assessments. There were 159 (70%) female and 68 (30%) male subjects. Average age and BMI were 17.4 years and 22.4 kg/m², respectively. Dynamic ultrasound accurately detected slipping rib in 97.4% (220/226; 94.3%, 99.0%) and correctly found no evidence in 88.7% (63/71; 79.0%, 95.0%) of studies, respectively. The combined right and left-sided sensitivity and specificity for morphology was 55.1% (50.2%, 60.0%) and 88.0% (83.0%, 92.9%); for the crunch maneuver, was 54.1% (49.2%, 59.0%) and 92.6% (88.6%, 96.6%); and, for the push maneuver, was 54.8% (50.0%, 59.7%) and 90.7% (86.2%, 95.2%).

CONCLUSION: Dynamic ultrasound imaging of the ribs is an effective and reproducible tool for the diagnosis of slipping rib syndrome, demonstrating high sensitivity and specificity in pediatric patients.

PMID:40613897 | DOI:10.1007/s00256-025-04961-y

Eur Radiol. 2025 Jul 4. doi: 10.1007/s00330-025-11797-6. Online ahead of print.

NO ABSTRACT

PMID:40613896 | DOI:10.1007/s00330-025-11797-6

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