Nevin Manimala

JAMA Oncol. 2025 Jan 2. doi: 10.1001/jamaoncol.2024.5636. Online ahead of print.

ABSTRACT

IMPORTANCE: The current standard-of-care salvage therapy in relapsed/refractory classic Hodgkin lymphoma (cHL) includes consolidation high-dose chemotherapy (HDCT)/autologous stem cell transplant (aSCT).

OBJECTIVE: To investigate whether presalvage risk factors and fludeoxyglucose-18 (FDG) positron emission tomography (PET) response to reinduction chemotherapy can guide escalation or de-escalation between HDCT/aSCT or transplant-free consolidation with radiotherapy to minimize toxic effects while maintaining high cure rates.

DESIGN, SETTING, AND PARTICIPANTS: EuroNet-PHL-R1 was a nonrandomized clinical trial that enrolled patients younger than 18 years with first relapsed/refractory cHL across 68 sites in 13 countries in Europe between January 2007 and January 2013. Data were analyzed between September 2022 and July 2024.

INTERVENTION: Reinduction chemotherapy consisted of alternating IEP (ifosfamide, etoposide, prednisolone) and ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). Patients with low-risk disease (late relapse after 2 cycles of first-line chemotherapy and any relapse with an adequate response after 1 IEP/ABVD defined as complete metabolic response on FDG-PET and at least 50% volume reduction) received a second IEP/ABVD cycle and radiotherapy (RT) to all sites involved at relapse. Patients with high-risk disease (all primary progressions and relapses with inadequate response after 1 IEP/ABVD cycle) received a second IEP/ABVD cycle plus HDCT/aSCT with or without RT.

MAIN OUTCOMES AND MEASURES: The primary end point was 5-year event-free survival. Secondary end points were overall survival (OS) and progression-free survival (PFS). PFS was identical to event-free survival because no secondary cancers were observed. PFS data alone are presented for simplicity.

RESULTS: Of 118 patients analyzed, 58 (49.2%) were female, and the median (IQR) age was 16.3 () years. The median (IQR) follow-up was 67.5 (58.5-77.0) months. The overall 5-year PFS was 71.3% (95% CI, 63.5%-80.1%), and OS was 82.7% (95% CI, 75.8%-90.1%). For patients in the low-risk group (n = 59), 41 received nontransplant salvage with a 5-year PFS of 89.7% (95% CI, 80.7%-99.8%) and OS of 97.4% (95% CI, 92.6%-100%). In contrast, 18 received HDCT/aSCT off protocol, with a 5-year PFS of 88.9% (95% CI, 75.5%-100%) and OS of 100%. All 59 patients with high-risk disease received HDCT/aSCT (and 23 received post-HDCT/aSCT RT) with a 5-year PFS of 53.3% (95% CI, 41.8%-67.9%) and OS of 66.5% (95% CI, 54.9%-80.5%).

CONCLUSION AND RELEVANCE: In this nonrandomized clinical trial, FDG-PET response-guided salvage in relapsed cHL may identify patients in whom transplant-free salvage achieves excellent outcomes. HDCT/aSCT may be reserved for primary progression and relapsed cHL with inadequate response.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00433459.

PMID:39745682 | DOI:10.1001/jamaoncol.2024.5636

Invest Ophthalmol Vis Sci. 2025 Jan 2;66(1):2. doi: 10.1167/iovs.66.1.2.

ABSTRACT

PURPOSE: To investigate the 10-year changes in visual function and incidence of visual impairment (VI) in highly myopic eyes.

METHODS: This longitudinal study enrolled highly myopic individuals who were followed up for 10 years. All participants underwent detailed ophthalmic examinations at baseline and follow-up visits. Best-corrected visual acuity (BCVA) was measured using Early Treatment of Diabetic Retinopathy Study protocol, and visual field (VF) was assessed with standard automatic perimetry.

RESULTS: A total of 568 highly myopic eyes (284 participants) were included, with mean baseline age of 22.49 ± 13.07 years, spherical equivalent refraction (SER) of -9.72 ± 3.02 D, and axial length of 27.39 ± 1.53 mm. Over 10 years, the mean BCVA loss was -0.06 logMAR (95% confidence internal [CI], 0.05-0.07). The mean change rates in mean deviation (MD) and pattern standard deviation over time were -0.07 dB/y (95% CI, -0.08 to -0.06) and 0.036 dB/y (95% CI, 0.028 to 0.044), respectively. The 10-year incidence of monocular moderate and severe VI (MSVI), per World Health Organization (WHO) and US criteria, was 3.52% (95% CI, 2.16%-5.39%) and 6.35% (95% CI, 4.46%-8.72%). Higher MSVI incidence, defined by WHO and US criteria, was associated with more myopic SER and lower baseline MD. Additionally, higher US-defined MSVI incidence was correlated with worse baseline BCVA.

CONCLUSIONS: In a highly myopic population, both BCVA and VF deteriorated over time, with increasing MSVI incidence. Raising public awareness of vision risks linked to high myopia and implementing strategies to reduce the burden in high-risk individuals are essential.

PMID:39745680 | DOI:10.1167/iovs.66.1.2

Health Psychol. 2025 Jan 2. doi: 10.1037/hea0001410. Online ahead of print.

ABSTRACT

OBJECTIVE: Although sexual minority men experience substantial discrimination, in addition to increased risk for several serious mental and somatic health problems, the biological mechanisms underlying these effects are unclear. To address this issue, we examined how experiences of social safety (i.e., community connection) and social threat (i.e., discrimination, in the forms of homophobia and racism) were related to conserved transcriptional response to adversity (CTRA) gene expression profiles across time, and whether these associations differed across HIV status, in a well-characterized, racially diverse sample of sexual minority men (M_age = 22.61, SD = 1.90).

METHOD: Experiences of community connection, homophobia, and racism were assessed via self-report, and blood samples were obtained at three timepoints over approximately 2 years. We then used these blood samples to characterize participants’ CTRA gene expression, which we quantified using an a priori 53-transcript composite score derived from RNA sequencing data from peripheral blood leukocytes.

RESULTS: As hypothesized, greater community connection was significantly related to decreased CTRA gene expression across time. These effects were similar regardless of HIV status and were robust to statistical adjustment for several potential confounding factors. In contrast, neither homophobia nor racism were related to CTRA gene expression.

CONCLUSION: These results suggest that community connection may be a protective factor that reduces biological processes known to negatively impact health. Consequently, interventions and policies aimed at reducing health disparities in marginalized populations may benefit from increasing community connection and inclusion. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:39745665 | DOI:10.1037/hea0001410

Methods Mol Biol. 2025;2886:177-199. doi: 10.1007/978-1-0716-4310-5_9.

ABSTRACT

Measurements of cell phylogeny based on natural or induced mutations, known as lineage barcodes, in conjunction with molecular phenotype have become increasingly feasible for a large number of single cells. In this chapter, we delve into Quantitative Fate Mapping (QFM) and its computational pipeline, which enables the interrogation of the dynamics of progenitor cells and their fate restriction during development. The methods described here include inferring cell phylogeny with the Phylotime model, and reconstructing progenitor state hierarchy, commitment time, population size, and commitment bias with the ICE-FASE algorithm. Evaluation of adequate sampling based on progenitor state coverage statistics is emphasized for interpreting the QFM results. Overall, this chapter describes a general framework for characterizing the dynamics of cell fate changes using lineage barcoding data.

PMID:39745641 | DOI:10.1007/978-1-0716-4310-5_9

Eur J Pediatr. 2025 Jan 2;184(1):114. doi: 10.1007/s00431-024-05923-7.

ABSTRACT

Knowledge about trends and epidemiology of pediatric burns is useful to identify patterns, to advance medical research, and to design prevention programs and resource allocation. The aim of this study is to describe the epidemiology and trends of pediatric burns between 2009 and 2022 in the three Dutch burn centers. A secondary objective of this study is to evaluate the influence of the COVID-19 pandemic on the pattern of pediatric burns. A register-based cohort study was conducted based on data from the Dutch Burn Repository R3. Patients between 0 and 17 years at the time of the burn injury admitted between 2009 and 2022 to one of the three burn centers were included. Descriptive statistics were used to investigate the incidence and patient, burn, and treatment characteristics. The COVID-19 pandemic years (2020-2021) were compared with the pooled results from pre-COVID-19 years (2017-2019). A total of 4017 patients were included in this study, of which 3085 (77%) were overnight admissions. The incidence and absolute number of pediatric burn admissions gradually increased over the years, with a small temporary decrease in 2020-2021. Patient and burn characteristics remained relatively consistent over the years. Three quarters of all patients were between 0 and 3 years old, and the majority were boys (59%). A decreasing ratio of length of stay per % total burned surface area and an increase in day admissions was observed since 2016 onwards, which intensified during the COVID-19 pandemic.

CONCLUSIONS: There was a slight increase in the number of pediatric admissions to the burn centers between 2009 and 2022. Young children (0-3 years) remain the most frequently affected group. A shorter relative length of stay was observed, as well as an increase in day admissions, which was reinforced by the COVID-19 pandemic.

WHAT IS KNOWN: • Burns are a leading cause of death and disability among children globally. The largest group affected are young children (0-3 years) and most are scald burns. • In the Netherlands, since the late nineties there has been a trend towards more admissions to specialized burn centers, especially for young children with less severe burns.

WHAT IS NEW: • There was a slight increase in the number of pediatric admissions to the burn centers between 2009 and 2022, with a temporary decrease during the COVID-19 pandemic (2020-2021). • Admissions now tend to be shorter per percentage total burned surface area (TBSA), with an increase in day admissions, which intensified during the COVID-19 years.

PMID:39745598 | DOI:10.1007/s00431-024-05923-7

AIDS Behav. 2025 Jan 2. doi: 10.1007/s10461-024-04601-x. Online ahead of print.

ABSTRACT

In the US, gay, bisexual, and other sexual minoritized men (GBSMM) remain disproportionately impacted by HIV, and continue to experience unmet needs for pre-exposure prophylaxis (PrEP). A growing body of literature has underscored the need to consider the geographic factors of HIV prevention, particularly beyond administrative boundaries and towards localized spaces that influence the accessibility and utilization of health-promoting resources. Therefore, the purpose of this study is to examine the associations of driving times from activity spaces to PrEP offering facilities and individual PrEP uptake. A total of 218 GBSMM (ages 18-34) from Connecticut and Georgia were sampled from a longitudinal cohort study. We used the getis-ord-gi statistic to examine the spatial clustering of PrEP offering facilities, and generalized estimating equations (GEE) and post-hoc moderation analyses to explore the state interactions on driving time and PrEP uptake. Our main findings suggest that for participants in Connecticut, state of residence was a significant moderator on driving time and ever hearing of PrEP and ever taking PrEP. Whereas for participants in Georgia, state of residence moderated the likelihood of returning to activity spaces of participants in both Connecticut and Georgia on PrEP uptake. These findings provide important direction for geographic inequities on PrEP use, but also a pragmatic method for co-creating and re-imagining place-health research. These results also offer an avenue to leverage the dynamic nuance of activity spaces as indicators to inform structural interventions for PrEP that are more equitable for GBSMM in small cities and towns in the U.S.

PMID:39745597 | DOI:10.1007/s10461-024-04601-x

Am J Physiol Gastrointest Liver Physiol. 2025 Jan 2. doi: 10.1152/ajpgi.00343.2024. Online ahead of print.

ABSTRACT

This study aimed to determine if local injection of CXCL12 reduces sphincter fibrosis, restores sphincter muscle content, vascularization, and innervation, and recruits progenitor cells in a rabbit model of anal sphincter injury and incontinence. Adult female rabbits were assigned to 3 groups: uninjured/no treatment (control), injured/treated (treated), and injured/no treatment (untreated) (n=4 each). Injured groups were anesthetized and a section of external anal sphincter was removed at the 9:00 o’clock position. The treated sphincters were injected with 200ng of human recombinant CXCL12 six weeks after injury and necropsy was performed six weeks post treatment. The external anal sphincter was removed, fixed, embedded in paraffin, sectioned, and mounted to slides for histologic analysis of collagen and muscle content and fiber characteristics; innervation, vascularization and progenitor cell content. Compared to controls untreated had significantly decreased total skeletal muscle, indistinct muscle layers, and disorganized circumferential and inner longitudinal layers at the injury site. Untreated also had significantly increased collagen fiber density at the injury site compared to treated and controls. Cells staining positive for CD34 within the skeletal muscle layer were increased in treated and untreated compared to controls. Staining density for markers of nerves and vascular endothelium, cells staining positive for CD34 within the mucosa/submucosae, and cells staining positive for PAX7 were similar among all groups. Local injection of CXCL12 reduces post-injury fibrosis and results in statistically similar muscle content and organization between treated animals and controls. Further studies are needed for this promising new treatment for post-parturient anal sphincter injury.

PMID:39745592 | DOI:10.1152/ajpgi.00343.2024

Neurol Sci. 2025 Jan 2. doi: 10.1007/s10072-024-07961-3. Online ahead of print.

ABSTRACT

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has shown potential in alleviating hemiplegic shoulder pain (HSP) and improving upper limb function, yet its efficacy remains debated. This study aims to assess the effectiveness of rTMS for HSP through a systematic review and meta-analysis.

METHODS: Four databases were searched with the keywords “rTMS” and “HSP”. Adults aged 18 years and older with post-stroke HSP were included. The primary outcomes were pain scores and upper limb function scores, and the secondary outcomewas the incidence of adverse events. The risk of bias was assessed through the ROB tool in Review Manager 5.4.1, and statistical analysis was primarily conducted through this software.

RESULTS: A total of 52 articles were identified from PubMed, Embase, Cochrane Library, and CNKI. Following literature screening, 11 studies were included in the analysis. The quality of the included studies was moderate.The studies encompassed 584 patients with post-stroke HSP and their average age was 62. The analysis revealed that rTMSwas significantly more effective in relieving pain compared to the control group (SMD = -1.14, p < 0.01), and low-frequency rTMSwas superior to high-frequency rTMS. In terms of improving upper limb function, rTMSwas also significantly more efficacious compared to the control group (SMD = 2.20, p < 0.01), and low-frequency and high-intensity rTMSwere more beneficial.

CONCLUSIONS: This study highlights the potential efficacy of rTMS. However, the heterogeneity among included studies, limited sample sizes, and lack of long-term follow-up data restrict the generalizability of the results.

PMID:39745590 | DOI:10.1007/s10072-024-07961-3

Pediatr Radiol. 2025 Jan 2. doi: 10.1007/s00247-024-06138-6. Online ahead of print.

ABSTRACT

BACKGROUND: Image-defined risk factors (IDRFs) were introduced to provide a consensus approach for pre-treatment risk stratification on computed tomography (CT) and magnetic resonance imaging (MRI) in patients with neuroblastoma.

OBJECTIVE: To assess the intra- and inter-reader agreement of radiologists in identifying IDRFs on CT.

MATERIALS AND METHODS: Approval for this retrospective study was granted by our institutional research ethics board with a waiver of consent. CT studies of pediatric patients with neuroblastoma were assessed by seven radiologists in two rounds. Each CT was accompanied by a standard form to indicate presence or absence of IDRFs for each patient. At least a 4-week period between rounds, randomization, and relabeling of the CT studies was required to minimize recall bias. Finally, three of the seven radiologists conducted a subsequent consensus reading to determine true positive IDRFs in the cohort. Fleiss’ kappa statistic was used to evaluate readers’ agreements and Pearson’s correlation assessed the correlation between years of experiences of radiologists and their performance in accurately (intra-reader agreement) detecting IDRFs.

RESULTS: A total of 31 children with a median age of 2.1 years (interquartile range (IQR) 1.1, 3.0; range 0-18; male=21 (67.7%)) were included and 251 total positive IDRFs were identified on their CT scans. The location of the primary tumor was in the neck in 1 patient (3.2%), within the chest in 2 patients (6.5%), within the abdomen in 27 patients (87.1%), and in the pelvis in 1 patient (3.2%). In determining IDRFs, the inter-reader agreement among radiologists was substantial: 0.65 (95% CI 0.60, 0.69) and the intra-reader agreement for each radiologist was substantial to near perfect, ranging from 0.67 (0.60, 0.70) to 0.86 (0.82, 0.90). The correlation between the number of years of experience of radiologists and their performances in accurately detecting IDRFs (their intra-reader agreements) was respectively low (r=45, P=0.30) for abdomino-pelvic IDRFs and high for organs’ infiltration IDRFs (r=0.74, P=0.05).

CONCLUSION: The determination of IDRFs on CT is reproducible with significant agreement among radiologists. The two IDRF items with the lowest overall inter-reader agreements were “diaphragm infiltration” and “mesenteric infiltration.”

PMID:39745539 | DOI:10.1007/s00247-024-06138-6

Abdom Radiol (NY). 2025 Jan 2. doi: 10.1007/s00261-024-04788-6. Online ahead of print.

ABSTRACT

OBJECTIVE: This study investigates the diagnostic value of Vesical Imaging Reporting and Data System (VI-RADS) in biparametric MRI (bp-MRI) for the detection of muscular infiltration in bladder cancer, and to investigate whether apparent diffusion coefficient (ADC) value can function as a potential indicator of bp-MRI VI-RADS for patient benefit.

MATERIALS AND METHODS: This single-center retrospective study enrolled 81 patients with pathologically confirmed bladder cancer from October 2019 to November 2021. Two readers independently scored the T2-weighted images and diffusion-weighted images of each index lesion based on the VI-RADS criteria, subsequently deriving the bp-MRI VI-RADS scores. Both ADC values and bp-MRI VI-RADS scores were utilized to develop a simple model by logistic regression. Receiver-operating characteristic curve assessed all systems, while decision curve analysis (DCA) and calibration curves evaluated the model’s performance.

RESULTS: The area under the curve (AUC) of bp-MRI VI-RADS was 0.886 (95% confidence interval [CI]: 0.801-0.971), with the diagnostic accuracy, sensitivity, and specificity being 0.753, 0.962, and 0.655 respectively. Regarding the ADC value, its AUC was 0.899 (95% CI: 0.821-0.977), and the diagnostic accuracy, sensitivity, and specificity were 0.877, 0.846, and 0.891. The AUC of the simple combined model achieved 0.942 (95% CI: 0.881-0.999), and the diagnostic accuracy, sensitivity, and specificity were 0.889, 0.885, and 0.891. The DeLong test verified that there was a statistically significant difference in AUC between the model and bp-MRI VI-RADS alone (P < 0.05). The simple model demonstrated excellent clinical applicability via DCA and calibration plots.

CONCLUSIONS: The contrast-free bp-MRI VI-RADS demonstrates commendable diagnostic efficacy for diagnosing muscular infiltration in bladder cancer. Additionally, ADC values can complement bp-MRI VI-RADS, enhancing diagnostic performance.

PMID:39745530 | DOI:10.1007/s00261-024-04788-6