Category: Nevin Manimala

Clin Cancer Res. 2024 Jun 7. doi: 10.1158/1078-0432.CCR-24-0150. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage, leveraging advanced imaging techniques to explore the relationship between tumor characteristics, glymphatic function, and aquaporin 4 (AQP4) expression.

EXPERIMENTAL DESIGN: In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index and Multiparametric MRI (MTP) for quantitative brain mapping. Tumor and peri-tumor tissues were analyzed for AQP4 expression via immunofluorescence. Correlations between imaging parameters, glymphatic function (DTI-ALPS index), and AQP4 expression were statistically assessed.

RESULTS: Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), brain tumor patients exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; p = 0.001) and increased cerebrospinal fluid (CSF) volume (201.376 cm³ vs. 115.957 cm³; p = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: -0.715, p < 0.001), while AQP4 expression correlated positively with peritumoral brain edema (PTBE) volume (r: 0.989; p < 0.001) and negatively with PD in PTBE areas (ρ: -0.506; p < 0.001).

CONCLUSIONS: Our findings highlight the interplay between tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, showing the utility of DTI-ALPS and MTP in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system.

PMID:38848042 | DOI:10.1158/1078-0432.CCR-24-0150

Drugs Aging. 2024 Jun 7. doi: 10.1007/s40266-024-01120-1. Online ahead of print.

ABSTRACT

BACKGROUND: Listing tools have been developed to improve medications in older patients, including the Fit fOR The Aged (FORTA) list, a clinically validated, positive-negative list of medication appropriateness. Here, we aim to validate MyFORTA, an automated tool for individualized application of the FORTA list.

METHODS: 331 participants of a multi-center cohort study (AgeCoDe) for whom the FORTA score (sum of overtreatment and undertreatment errors) had been determined manually (gold standard [GS]) were reassessed using the automated MyFORTA (MF) tool. This tool determines the score from ATC and ICD codes combined with clinical parameters.

RESULTS: The FORTA scores were 9.01 ± 2.91 (mean ± SD, MF) versus 6.02 ± 2.52 (GS) (p < 0.00001). Removing undertreatment errors for calcium/vitamin D (controversial guidelines) and influenza/pneumococcal vaccinations (no robust information in the database), the difference decreased: 7.5 ± 2.7 (MF) versus 5.98 ± 2.55 (GS) (p < 0.00001). The remaining difference was driven by, for example, missing nitro spray in coronary heart disease/acute coronary syndrome as the related information was rarely found in the database, but notoriously detected by MF. Three hundred and forty errors from those 100 patients with the largest score deviation accounted for 68% of excess errors by MF.

CONCLUSION: MF was more sensitive to detect medication errors than GS, all frequent errors only detected by MF were plausible, and almost no adaptations of the MF algorithm seem indicated. This automated tool to check medication appropriateness according to the FORTA list is now validated and represents the first clinically directed algorithm in this context. It should ease the application of FORTA and help to implement the proven beneficial effects of FORTA on clinical endpoints.

PMID:38848020 | DOI:10.1007/s40266-024-01120-1

J Autism Dev Disord. 2024 Jun 7. doi: 10.1007/s10803-024-06405-3. Online ahead of print.

ABSTRACT

The purpose of this study was to test the use of Pivotal Response Treatment (PRT) in the secondary school setting. There were two main goals: (a) to evaluate secondary education providers’ ability to implement PRT with fidelity following a PRT training program; and (b) to evaluate the effects of school-implemented PRT on the social communication skills of adolescents and young adults with ASD, specifically, question-asking behavior. This concurrent multiple baseline design study across dyads investigated the use of PRT in the secondary school setting with adolescents with ASD. Specifically, it examined the impact of PRT on question-asking behavior. Education providers (n = 3) were trained to implement PRT with a secondary student with ASD. All education providers improved in their ability to use PRT strategies, though struggled with fidelity. Two students exhibited clear effects with noteworthy improvement in their use of targeted question initiations. For targeted question initiations, the weighted value for the Tau-U phase contrast between aggregated baseline and intervention phases was 0.80 and statistically significant (p < .0001). PRT is a promising approach to increasing question-asking behavior in secondary students with ASD when implemented by a trained education provider. Continued research should be a matter of priority in order to expand social skills instruction for adolescents with ASD with the hope of ultimately making a positive difference in adult outcomes.

PMID:38848010 | DOI:10.1007/s10803-024-06405-3

J Interv Card Electrophysiol. 2024 Jun 7. doi: 10.1007/s10840-024-01831-w. Online ahead of print.

ABSTRACT

BACKGROUND: Catheter ablation is recognized as an effective treatment for atrial fibrillation (AF). Despite its effectiveness, significant sex-specific differences have been observed, which influence the outcomes of the procedure. This study explores these differences in a cohort of patients with persistent AF. We aim to assess sex differences in baseline characteristics, symptoms, quality of life, imaging findings, and response to catheter ablation in patients with persistent AF.

METHODS: This post hoc analysis of the DECAAF II trial evaluated 815 patients (161 females, 646 males). Between July 2016 and January 2020, participants were enrolled and randomly assigned to receive either personalized ablation targeting left atrial (LA) fibrosis using DE-MRI in conjunction with pulmonary vein isolation (PVI) or PVI alone. In this analysis, we aimed to compare female and male patients in the full cohort in terms of demographics, risk factors, medications, and outcomes such as AF recurrence, AF burden, LA volume reduction assessed by LGE-MRI before and 3 months after ablation, quality of life assessed by the SF-36 score, and safety outcomes. Statistical methods included t-tests, chi-square, and multivariable Cox regression.

RESULTS: Females were generally older with more comorbidities and experienced higher rates of arrhythmia recurrence post-ablation (53.3% vs. 40.2%, p < 0.01). Females also showed a higher AF burden (21% vs. 16%, p < 0.01) and a smaller reduction in left atrial volume indexed to body surface area post-ablation compared to male patients (8.36 (9.94) vs 11.35 (13.12), p-value 0.019). Quality of life scores were significantly worse in females both pre- and post-ablation (54 vs. 66 pre-ablation; 69 vs. 81 post-ablation, both p < 0.01), despite similar improvements across sexes. Safety outcomes and procedural parameters were similar between male and female patients.

CONCLUSION: The study highlights significant differences in the outcomes of catheter ablation of persistent AF between sexes, with female patients showing worse quality of life, higher recurrence of AF and AF burden after ablation, and worse LA remodeling.

PMID:38848006 | DOI:10.1007/s10840-024-01831-w

Musculoskelet Surg. 2024 Jun 7. doi: 10.1007/s12306-024-00840-2. Online ahead of print.

ABSTRACT

BACKGROUND: Major musculoskeletal oncology procedures often result in perioperative bleeding. This exposes patients to allogeneic red blood cell transfusion and its potential complications, thus increasing the risk of surgical wound infection and prolonged hospital stay. This study aimed to investigate the efficacy of oxidised cellulose, a topical haemostatic agent, in reducing postoperative blood loss and its subsequent risks.

METHODS: In this randomised controlled trial, 40 patients undergoing major musculoskeletal oncology procedures were assigned to control and intervention groups. Oxidised cellulose was inserted into the surgical wound after the resection’s conclusion before the wound’s closure to reduce postoperative bleeding for patients in the intervention group. Postoperative closed suction drain system (Redivac TM) volume, drop in haemoglobin level, allogeneic red blood cell transfusion rate, duration of surgery, and length of hospital stay were compared between the two groups.

RESULTS: The postoperative Redivac volume (Control: 432 MLS vs. Intervention: 431.75 MLS), drop in haemoglobin level (Control: 3.12 g/dL vs. Intervention: 3.06 g/dL), duration of surgery (Control: 134 vs. Intervention: 156 min), and allogeneic red blood cell transfusion were lower in the intervention group (Control: 204 MLS vs. Intervention: 170 MLS), but they were not statistically significant (p > 0.05) (Control: 134 vs. Intervention: 156 min). Mean hospital stay was similar in both groups (Control: 5.45 days vs. Intervention: 5.85 days).

CONCLUSION: Oxidised cellulose use does not significantly affect postoperative blood loss, the rate of allogeneic blood transfusion, and hospital stay. However, we believe its use contributes positively but not considerably towards lower postoperative blood loss in musculoskeletal oncology surgeries.

PMID:38848000 | DOI:10.1007/s12306-024-00840-2

Matern Child Health J. 2024 Jun 7. doi: 10.1007/s10995-024-03941-3. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the association between air pollution exposure and housing context during pregnancy and adverse birth outcomes.

METHODS: We linked air pollution data from the Environmental Protection Agency and housing data from the American Community Survey with birth records from Wisconsin counties over a 9-year period. We calculated average daily pregnancy exposure to fine particulate matter and ozone and modeled its relationship to preterm birth, low birthweight and NICU admission, adjusting for individual characteristics and housing context.

RESULTS: Ozone exposure and housing cost-burden had substantive and statistically significant negative associations with birthweight and gestational age, and positive associations with NICU admission, while a poor-quality housing environment had a significant negative effect on weeks of gestation. Fine particulate matter exposure had a negligible correlation with these outcomes.

CONCLUSIONS FOR PRACTICE: An additional tenth of one part-per-million daily average exposure to ozone is associated with a 33 g decrease in birthweight. This decrease in birthweight is about the same size as the association of gestational diabetes (32 g), larger than the association of chronic hypertension (22 g), and about 40% the size of the effect of smoking during pregnancy on birthweight (84 g). Given the magnitudes of the associations with atmospheric ozone and adverse birth outcomes, reducing atmospheric ozone should be a public health priority. Inclusion of controls for housing cost-burden and poor-quality housing reduces the magnitude of the association with mothers who identify as Black, suggesting the importance of these structural factors in understanding adverse birth outcomes by race.

PMID:38847990 | DOI:10.1007/s10995-024-03941-3

Mycopathologia. 2024 Jun 7;189(3):48. doi: 10.1007/s11046-024-00862-1.

ABSTRACT

The impact of invasive pulmonary aspergillosis (IPA) on non-neutropenic critically ill patients in intensive care units (ICU) has been demonstrated in recent decades. Furthermore, after the start of the COVID-19 pandemic, COVID-19 associated with pulmonary aspergillosis (CAPA) has become a major concern in ICUs. However, epidemiological data from different regions are scarce. We evaluated the prevalence and clinical-epidemiological data of IPA in patients with COVID-19 requiring mechanical ventilation (MV) in the ICU (“severe COVID-19”) and non-COVID ICU patients in MV of a tertiary hospital in the southern region of Brazil. Eighty-seven patients admitted between June 2020 and August 2022 were included; 31 with severe COVID-19. For the diagnosis of IPA or CAPA, algorithms including host factors and mycological criteria (positive culture for Aspergillus spp., immunoassay for galactomannan detection, and/or qPCR) were utilized. The overall incidence of IPA and CAPA in our ICU was 73 cases/1000 ICU hospitalizations. Aspergillosis occurred in 13% (4/31) of the COVID-19 patients, and in 16% (9/56) of the critically ill patients without COVID-19, with mortality rates of 75% (3/4) and 67% (6/9), respectively. Our results highlight the need for physicians enrolled in ICU care to be aware of aspergillosis and for more access of the patients to sensitive and robust diagnostic tests by biomarkers detection.

PMID:38847987 | DOI:10.1007/s11046-024-00862-1

Ann Surg Oncol. 2024 Jun 7. doi: 10.1245/s10434-024-15510-7. Online ahead of print.

ABSTRACT

BACKGROUND: The objective of this meta-analysis was to assess the association of sarcopenia defined on computed tomography (CT) head and neck with survival in head and neck cancer patients.

METHODS: Following a PROSPERO-registered protocol, two blinded reviewers extracted data and evaluated the quality of the included studies using the Quality In Prognostic Studies (QUIPS) tool, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. A meta-analysis was conducted using maximally adjusted hazard ratios (HRs) with the random-effects model. Heterogeneity was measured using the I² statistic and was investigated using meta-regression and subgroup analyses where appropriate.

RESULTS: From 37 studies (11,181 participants), sarcopenia was associated with poorer overall survival (HR 2.11, 95% confidence interval [CI] 1.81-2.45; p < 0.01), disease-free survival (HR 1.76, 95% CI 1.38-2.24; p < 0.01), disease-specific survival (HR 2.65, 95% CI 1.80-3.90; p < 0.01), progression-free survival (HR 2.24, 95% CI 1.21-4.13; p < 0.01) and increased chemotherapy or radiotherapy toxicity (risk ratio 2.28, 95% CI 1.31-3.95; p < 0.01). The observed association between sarcopenia and overall survival remained significant across different locations of cancer, treatment modality, tumor stages and geographical region, and did not differ between univariate and multivariate HRs. Statistically significant correlations were observed between the C3 and L3 cross-sectional area, skeletal muscle mass, and skeletal muscle index.

CONCLUSIONS: Among patients with head and neck cancers, CT-defined sarcopenia was consistently associated with poorer survival and greater toxicity.

PMID:38847986 | DOI:10.1245/s10434-024-15510-7

Ann Surg Oncol. 2024 Jun 7. doi: 10.1245/s10434-024-15500-9. Online ahead of print.

ABSTRACT

BACKGROUND: Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is an aggressive histopathologic subtype of papillary thyroid carcinoma. Correlation between genotype and phenotype has not been comprehensively described. This study aimed to describe the genomic landscape of DSPTC comprehensively using next-generation sequencing (NGS), analyze the prognostic implications of different mutations, and identify potential molecular treatment targets.

METHODS: Tumor tissue was available for 41 DSPTC patients treated at Memorial Sloan Kettering Cancer Center between 2004 and 2021. After DNA extraction, NGS was performed using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets platform, which sequences 505 critical cancer genes. Clinicopathologic characteristics were compared using the chi-square test. The Kaplan-Meier method and log-rank statistics were used to compare outcomes.

RESULTS: The most common mutation was RET fusion, occurring in 32% (13/41) of the patients. Other oncologic drivers occurred in 68% (28/41) of the patients, including 8 BRAF^V600E mutations (20%) and 4 USP8 mutations (10%), which have not been described in thyroid malignancy previously. Patients experienced RET fusion-positive tumors at a younger age than other drivers, with more aggressive histopathologic features and more advanced T stage (p = 0.019). Patients who were RET fusion-positive had a significantly poorer 5-year recurrence-free survival probability than those with other drivers (46% vs 84%; p = 0.003; median follow-up period, 45 months). In multivariable analysis, RET fusion was the only independent risk factor for recurrence (hazard ratio [HR], 7.69; p = 0.017).

CONCLUSION: Gene-sequencing should be strongly considered for recurrent DSPTC due to significant prognostic and treatment implications of RET fusion identification. The novel finding of USP8 mutation in DSPTC requires further investigation into its potential as a driver mutation.

PMID:38847983 | DOI:10.1245/s10434-024-15500-9

Arch Dermatol Res. 2024 Jun 7;316(7):340. doi: 10.1007/s00403-024-03075-0.

ABSTRACT

Psoriasis (PsO) is a chronic inflammatory skin condition, often accompanied by psoriatic arthritis (PsA) and linked to various comorbidities and increased mortality rates. This study aimed to explore the relationship between PsO and accelerated biological aging, specifically focusing on epigenetic DNA methylation clocks. Using a matched case-control design, 20 PsO cases were selected along with age, race, and sex-matched 20 controls without PsO from the Skin Disease Biorepository at Brown Dermatology, Inc, Providence, Rhode Island. Blood samples retrieved from both groups were analyzed for DNA methylation, and epigenetic ages were calculated using DNA methylation clocks, including Horvath, Hannum, Pheno, SkinBlood, and Grim ages. Generalized estimation equations were employed to test the differences in epigenetic and chronological ages between PsO cases and controls, as well as within various subgroups in comparison to their respective controls. There were no statistically significant differences in epigenetic ages between PsO cases and controls. However, notably, PsO cases with PsA demonstrated an accelerated PhenoAge, compared to their matched controls. This study represents a pioneering investigation into the potential link between PsO and epigenetic aging, shedding light on the possibility of accelerated epigenetic aging in PsA, possibly associated with heightened inflammatory burden. These findings emphasize the systemic impact of PsA on the aging process, prompting the need for deeper exploration into autoimmune pathways, inflammation, and epigenetic modifications underlying PsO pathogenesis and aging mechanisms. Larger-scale studies with diverse populations are imperative to discern PsO subgroups experiencing accelerated biological aging and decipher the intricate interplay between PsO, inflammation, and aging pathways.

PMID:38847964 | DOI:10.1007/s00403-024-03075-0