Category: Nevin Manimala

Blood Adv. 2025 Jul 2:bloodadvances.2024015659. doi: 10.1182/bloodadvances.2024015659. Online ahead of print.

ABSTRACT

Measurement of patient-reported outcomes (PROs) and health-related quality of life (HrQOL) are crucial for comprehensive, patient-centered cancer care. Both PROs and HrQOL have been under-studied in patients with Erdheim-Chester disease (ECD), a rare cancer with protean manifestations, dense symptomatology, and frequent diagnostic delay. We sought to evaluate the longitudinal evolution of symptom burden and unmet supportive care needs in patients with ECD, and to identify associations between these PROs and HrQOL. A registry-based cohort of patients with ECD completed a PRO battery including the Functional Assessment of Cancer Therapy-General (FACT-G) and other validated PRO measures. Descriptive statistics were used to characterize the distribution of PROs and FACT-G scores; PROs were modeled by univariable linear regression with FACT-G total score as the dependent variable at (1) registry enrollment and (2) 12-month time points. Changes in FACT-G total score (the difference between the 12-month and enrollment scores) were correlated with changes in PROs using univariable linear regression analysis. In 158 patients, mean total FACT-G was 70.8, lower than observed across multiple cancer cohorts. Higher levels of pain and fatigue, presence of neurologic symptoms, and greater number of unmet needs were all associated with worse HrQOL. Improvement in pain, fatigue, and unmet needs over 12 months was significantly associated with improvement in HrQOL. In patients with ECD, HrQOL is substantially diminished, even when considering other patients with cancer. Mitigation of symptoms and addressing unmet supportive care needs represent opportunities for intervention to improve HrQOL in ECD.

PMID:40601910 | DOI:10.1182/bloodadvances.2024015659

J Clin Oncol. 2025 Jul 2:JCO2501041. doi: 10.1200/JCO-25-01041. Online ahead of print.

NO ABSTRACT

PMID:40601891 | DOI:10.1200/JCO-25-01041

JCO Oncol Pract. 2025 Jul 2:OP2500462. doi: 10.1200/OP-25-00462. Online ahead of print.

ABSTRACT

PURPOSE: Advances in breast cancer treatment have reduced mortality and toxicity, but it remains unclear which patients receive updated care and when. We aimed to identify factors associated with receiving updated breast cancer care.

METHODS: We analyzed patients age 65-85 years with local or regional breast cancer, diagnosed between 2010 and 2018, using the SEER-Medicare database. We included patients who were continuously enrolled in Medicare for 1 year after diagnosis and were eligible for one of four updated treatments: (1) adjuvant paclitaxel-trastuzumab (APT) for human epidermal growth factor receptor 2 (HER2)-positive local disease, (2) pertuzumab for HER2-positive regional disease, (3) neoadjuvant chemotherapy for triple-negative or HER2-positive regional disease, and (4) omission of chemotherapy for hormone receptor-positive, HER2-negative regional disease. We examined the association between treating oncologist specialization (percent of SEER-Medicare patients with breast cancer) and receipt of updated care using multivariable analysis.

RESULTS: Of the 21,575 patients eligible for one of these four updated care approaches, use of the APT regimen increased from 30% (95% CI, 23% to 37%) to 72% (95% CI, 67% to 77%), pertuzumab from 0% to 71% (95% CI, 66% to 76%), neoadjuvant chemotherapy from 23% (95% CI, 18% to 28%) to 60% (95% CI, 56% to 65%), and omission of chemotherapy from 54% (95% CI, 52% to 57%) to 61% (95% CI, 59% to 64%) from 2010 to 2018. In multivariable analyses, higher median income of residence county and greater specialization of treating oncologist were statistically significantly associated with receipt of updated care for all four treatment scenarios. Patients from lower-income areas who received care from more specialized oncologists were as likely to receive updated care as those from higher-income areas.

CONCLUSION: Patients from lower-income areas were less likely to receive updated care, but specialized oncologists helped mitigate this disparity. Care models that expand consultative access to specialized oncologists should be prioritized for evaluation.

PMID:40601879 | DOI:10.1200/OP-25-00462

Ocul Immunol Inflamm. 2025 Jul 2:1-9. doi: 10.1080/09273948.2025.2519851. Online ahead of print.

ABSTRACT

OBJECTIVE: We conducted this present meta-analysis to examine the difference in efficacy and safety of intravitreal dexamethasone implant (DEXI) in vitrectomized and non-vitrectomized eyes.

METHODS: All types of comparative studies published on PubMed, CENTRAL, Scopus, and Embase databases till March 10, 2025 were included. We conducted a random-effects meta-analysis for change in central macular thickness (CMT), best corrected visual acuity (BCVA) (as logMar), and rise in intraocular pressure (IOP).

RESULTS: Thirteen studies were included comparing 365 vitrectomized eyes with 778 non-vitrectomized eyes. Studies included mixed etiologies of macular edema. Meta-analysis showed that change in CMT was not significantly different between the two groups at 1 month (MD: -11.34 95% CI: -47.51, 24.82 I² = 2%), 3 months (MD: -0.43 95% CI: -33.36, 32.5 I² = 44%), 6 months (MD: -0.69 95% CI: -33.57, 34.95 I² = 18%) or 12 months ((MD: 37.46 95% CI: -4.86, 79.77 I² = 86%). The pooled analysis found no statistically significant difference between the two groups for change in BCVA at 1 month (MD: 0.04 95% CI: -0.01, 0.09 I² = 32%), 3 months (MD: 0.04 95% CI: -0.02, 0.09 I² = 0%) and 6 months (MD: 0.06 95% CI: 0.00, 0.11 I² = 0%). However, change in BCVA was significantly higher in the vitrectomized group at 12 months (MD: 0.17 95% CI: 0.13, 0.22 I² = 54%). The meta-analysis found no statistically significant difference in the risk of a rise in IOP between the two groups (OR: 1.26 95% CI: 0.81, 1.95 I² = 0%). Subgroup analysis based on etiology did not change the results.

CONCLUSIONS: DEXI may be equally efficacious and safe in vitrectomized and non-vitrectomized eyes.

PMID:40601878 | DOI:10.1080/09273948.2025.2519851

J Am Chem Soc. 2025 Jul 2. doi: 10.1021/jacs.5c08517. Online ahead of print.

ABSTRACT

Chirality-induced spin selectivity (CISS), which refers to the ability of chiral molecules to preferentially select spins during electron transfer, has attracted great attention during the past two decades. However, the theoretical and experimental understanding of the CISS effect remains preliminary. In this study, we demonstrate that there is no distinguishable CISS effect in the case of coherent electron transport through single chiral molecular junctions for a set of four molecule studied here. Our conclusion is based on statistical evaluations of thousands of single-molecule junctions across four different molecules with different origins of chirality measured by the scanning tunneling microscope-based break-junction technique. The experimental results for all molecules show no dependence on external magnetic field or chirality in both conductance and current-voltage measurements. In addition, ab initio Hartree-Fork calculations combined with the nonequilibrium Green’s function method reveal that the spin-orbit coupling within chiral junctions bound to a few gold atoms is generally too weak to induce detectable spin polarizations from spin flipping or spin filtering during the ultrafast electron-transport time scale. The absence of an observable CISS effect in the coherent electron-transport regime suggests that the effect may only be found in other electron-transfer regimes and requires further experimental and theoretical efforts to achieve a comprehensive understanding.

PMID:40601876 | DOI:10.1021/jacs.5c08517

Bioconjug Chem. 2025 Jul 2. doi: 10.1021/acs.bioconjchem.5c00168. Online ahead of print.

ABSTRACT

Glioblastoma Multiforme (GBM) represents a significant clinical challenge among central nervous system tumors, with a dismal mean survival rate of less than 8 months, a statistic that has remained largely unchanged for decades (National Brain Society, 2022). The specialized intricate anatomical features of the brain, notably the blood-brain barrier (BBB), pose significant challenges to effective therapeutic interventions, limiting the potential reach of modern advancements in immunotherapy to impact these types of tumors. This study introduces an innovative, actively targeted immunotherapeutic nanoconjugate (P-12/AP-2/NCs) designed to serve as an immunotherapeutic agent capable of traversing the BBB via LRP-1 receptor-mediated transcytosis. P-12/AP-2/NCs exert their immune-modulating effects by inhibiting the PD-1/PD-L1 axis through a small-sized PD-L1/PD-L2 antagonist peptide, Aurigene NP-12 (P-12). P-12/AP-2/NCs are synthesized from completely biodegradable, functionalized high molecular weight β-poly(l-malic acid) (PMLA) polymer conjugated with P-12 and Angiopep-2 (AP-2) to yield P-12/AP-2/NCs. Evaluating nanoconjugates for BBB permeability and 3D tumor model efficacy using an in vitro BBB-Transwell spheroid-based model demonstrated successful crossing of the BBB and internalization in brain 3D tumor environments. In addition, the nanoconjugate mediated T cells’ cytotoxicity on 3D tumor region death in a U87 GBM 3D spheroid model. AP-2/P-12/NCs are selectively inhibited in PD1/PDL1 interaction on T cells and the tumor site, increasing inflammatory cytokine secretion and T cell proliferation. In an in vivo murine brain environment, rhodamine fluorophore-labeled AP-2/P-12/NCs displayed significantly increased accumulation in the brain during 2-6 h time intervals postinjection with a prolonged bioavailability over unconjugated peptides. AP-2/P-12/NCs demonstrated a safety profile at both low and high doses based on major organ histopathology evaluations. Our findings introduce a novel, programmable nanoconjugate platform capable of penetrating the BBB for directed delivery of small peptides and significant immune environment modulation without utilizing antibodies, offering promise for treating challenging brain diseases such as glioblastoma multiforme and beyond.

PMID:40601862 | DOI:10.1021/acs.bioconjchem.5c00168

Age Ageing. 2025 Jul 1;54(7):afaf180. doi: 10.1093/ageing/afaf180.

ABSTRACT

BACKGROUND: Despite the well-documented health benefits of Physical Activity (PA), older adults often struggle to engage in PA. The present review examines the relationship between PA, motivation and basic psychological needs among older adults aged 65 and over, through the lens of Self-Determination Theory (SDT).

METHODS: Relevant studies that used qualitative methodologies and applied SDT framework were systematically searched in five electronic databases (i.e. Scopus, Web of Science, PubMed, PsycINFO and CINAHL). Methodological rigour was assessed using the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative Research).

RESULTS: 21 studies met inclusion criteria (N = 412; ages 65-97). Four themes and nine subthemes were identified. Peer relationships emerged as a pivotal element in supporting most autonomous forms of motivation and satisfying psychological needs (i.e. autonomy, competence and relatedness). A peer coach was preferred during several health programs, enhancing competence and relatedness. Outdoor activities in natural settings promoted intrinsic motivation, while indoor activities were driven more by extrinsic motivation. Barriers included ageist stereotypes and perceptions of inevitable physical decline, which negatively impacted competence and autonomy, ultimately reducing motivation for PA.

CONCLUSIONS: This qualitative synthesis highlights a complex interplay of SDT components and social factors in influencing PA behaviours among older adults. Tailored interventions that integrate social interaction, provide feedback from coaches and offer choices among several exercises with graduate intensity levels are likely to enhance adherence in PA. Future interventions should address both psychological and social barriers to create inclusive PA strategies that meet older adults’ needs and motivation.

PMID:40601367 | DOI:10.1093/ageing/afaf180

J Vet Med Educ. 2025 Jun 30:e20240165. doi: 10.3138/jvme-2024-0165. Online ahead of print.

ABSTRACT

Lameness in horses resulting from foot pathology is very common. When investigating the cause of a lameness localised to the foot, the first step is most frequently radiographic imaging. Therefore, being able to identify normal anatomy and recognise pathology on radiographs is important for a veterinary medicine student to learn. Computer-aided learning (CAL) is becoming increasingly utilised in the teaching of students on medicine-related courses, especially post-COVID where online learning has been continued in hybridisation with in-person teaching.In this study, a low-cost CAL module was created focusing on anatomy and pathology of the equine foot on radiographic images and testing was carried out to evaluate how beneficial students found this resource for their learning. There were two research questions: 1. Can a useful CAL module be produced at low cost? 2. Will this CAL module function to increase student confidence? The CAL module was produced at no cost; similar CAL modules could be easily re-created using a similar module at a low-to-no cost. Three skills were reviewed: recognition of normal anatomy, identification of pathology, and selection of appropriate radiographic views for investigation of specific pathologies. A statistically significant increase in confidence of students’ ability to recognise pathology and to select radiographic views for investigating specific pathologies when comparing pre- and post-resource confidence. Anecdotally there was a positive response to the resource: users found it useful for the intended purpose. Therefore, a useful CAL module was produced at low cost, and did indeed increase students’ confidence in some areas investigated.

PMID:40601339 | DOI:10.3138/jvme-2024-0165

Am Surg. 2025 Jul 2:31348251358439. doi: 10.1177/00031348251358439. Online ahead of print.

ABSTRACT

IntroductionTransanal minimally invasive surgery (TAMIS) is a technique used for the management of low rectal neoplasms in properly selected patients. Transanal minimally invasive surgery may be performed using either laparoscopic or robotic platforms. Little data exists in the literature comparing the two. We hypothesize that the use of the robotic platform will facilitate superior outcomes due the advantages of the robotic platform in terms of its superior maneuverability, ease of suturing, and 3-dimensional visualization.MethodsThis retrospective study included adults who underwent a TAMIS via a robotic or laparoscopic approach in a rural tertiary care hospital between January 2016 and December 2023. Following IRB approval, patients who underwent TAMIS were identified using CPT codes 45171, 45172, 0184T, and S2900. Chart review was performed comparing approaches. Variables included patient demographics, operative time, blood loss, need for reoperation, presence of positive margins, and cost. Outcomes were compared using Fisher’s Exact and Mann-Whitney U-tests (SPSS version 22.0, IBM, Armonk NY).ResultsTwenty-seven patients met inclusion criteria (19 laparoscopic and 8 robotic). Both groups did not differ significantly in age (65.47 ± 12.16 vs 54.75 ± 19.09, P = 0.26) and sex (male, 73.7% vs 75.0%, P = 1.00). Outcomes did not differ statistically across the two groups with respect to operative time (1.54 ± 0.58 vs 1.35 ± 0.22 hours, P = 0.33), blood loss (89.5% minimal vs 100.0% minimal, P = 1.00), and incidence of positive margins (10.5% vs 12.5%, P = 1.00). The cost of the laparoscopic TAMIS was significantly lower ($2271/case vs $15,948/case, P < 0.001) compared to the robotic TAMIS approach.ConclusionsLaparoscopic and robotic TAMIS yield comparable results, but the laparoscopic approach is much less costly. Prospective studies comparing surgical outcomes and procedural costs are therefore warranted.

PMID:40601337 | DOI:10.1177/00031348251358439

JAMA Dermatol. 2025 Jul 2. doi: 10.1001/jamadermatol.2025.1976. Online ahead of print.

ABSTRACT

IMPORTANCE: There is limited comparative information on regulatory approved and pipeline treatments in hidradenitis suppurativa (HS).

OBJECTIVE: To compare efficacy, safety, and tolerability of treatments for moderate to severe HS.

DATA SOURCES: MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from inception to June 28, 2024.

STUDY SELECTION: Phase 2 and 3 randomized clinical trials of medical interventions (cytokine inhibitors, small molecule inhibitors, cell inhibitors, and other novel immune or inflammatory modifiers) for adults with moderate to severe HS having primary efficacy assessments between 12 and 16 weeks.

DATA EXTRACTION AND SYNTHESIS: Data extraction and risk of bias assessments were performed independently by 2 reviewers. Efficacy outcomes were analyzed using random-effects network meta-analysis. Safety and tolerability outcomes were analyzed using pairwise fixed-effect meta-analyses vs placebo. Data analysis was performed between August 22, 2024, and April 7, 2025.

MAIN OUTCOMES AND MEASURES: Primary efficacy, safety, and tolerability outcomes were Hidradenitis Suppurativa Clinical Response (HiSCR)-50, occurrence of serious adverse events (SAEs), and treatment discontinuation due to adverse events, respectively. HiSCR-75 was a secondary efficacy outcome.

RESULTS: Of 26 eligible trials, 25 had available HiSCR-50 data, including 5767 total patients and 39 unique treatments. Compared with placebo, the following treatments were associated with significantly higher HiSCR-50 response rates: sonelokimab, 120 mg, every 4 weeks; lutikizumab, 300 mg, every 2 weeks; adalimumab, 40 mg, once per week; sonelokimab, 240 mg, every 2 weeks; bimekizumab, 320 mg, every 2 weeks; povorcitinib, 15 mg, once per day; bimekizumab, 320 mg, every 4 weeks; secukinumab, 300 mg, every 4 weeks; and secukinumab, 300 mg, every 2 weeks. Most differences between adalimumab, 40 mg, once per week, and other targeted treatments were not statistically significant. The percentage of patients experiencing SAEs ranged from 0% to 10% in the placebo groups, 0% to 8% in the adalimumab (40 mg, once per week) groups, and 0% to 6% in the other active treatment groups. The percentage of patients discontinuing treatment due to adverse events ranged from 0% to 10% in the placebo groups, 0% to 4% in the adalimumab (40 mg, once per week) groups, and 0% to 15% (ropsacitinib) in the other active treatment groups.

CONCLUSIONS AND RELEVANCE: This network meta-analysis provides evidence for the comparative efficacy and safety of currently approved and pipeline medications for moderate to severe HS in the absence of head-to-head trials.

PMID:40601333 | DOI:10.1001/jamadermatol.2025.1976