Nevin Manimala

Sci Total Environ. 2023 Jul 18:165588. doi: 10.1016/j.scitotenv.2023.165588. Online ahead of print.

ABSTRACT

BACKGROUND: Although emerging studies have illuminated the protective association between greenness and respiratory mortality, efforts to quantify the potentially complex role of air pollution in the causal pathway are still limited. We aimed to examine the potential roles of air pollution in the causal pathway between greenness and respiratory mortality in China.

METHODS: We used data from a community-based prospective cohort of 654,115 participants in southern China (Jan 2009-Dec 2020). We evaluated the greenness exposure as a three-year moving average Normalized Difference Vegetation Index (NDVI) within the 500 m buffer around the residence. Cox proportional hazards model was applied to estimate the association between greenness and respiratory mortality. Causal mediation analysis combined with a four-way dimensional decomposition method was utilized to simultaneously quantify the interaction and mediation role of air pollution including PM_2.5, PM₁₀, or NO₂ on the greenness-respiratory mortality relationship.

FINDINGS: We observed 6954 respiratory deaths during 12 years of follow-up. Increasing NDVI level from the lowest to the highest quartile is associated with a 19 % (95%CI: 13-25 %) reduction in the respiratory mortality risk. For the total protective effect, the proportion attributable to the overall negative interaction between greenness and air pollution (PM_2.5, PM_10, or NO₂) was 2.2 % (1.7-3.2 %), 3.5 % (0.4-3.7 %), or 25.0 % (22.8-27.1 %), respectively. Simultaneously, we estimated 25.5 % (20.1-32.0 %), 49.5 % (32.5-71.9 %), or 1.0 % (0.8-1.2 %) of the total protective association was mediated through a reduction in PM_2.5, PM₁₀, or NO₂, respectively.

INTERPRETATION: Increased greenness exposure mitigated respiratory mortality through both the antagonistic interaction and mediation pathway of air pollution (PM_2.5, PM₁₀, or NO₂).

PMID:37474059 | DOI:10.1016/j.scitotenv.2023.165588

Orthop Traumatol Surg Res. 2023 Jul 18:103661. doi: 10.1016/j.otsr.2023.103661. Online ahead of print.

ABSTRACT

BACKGROUND: Trochanteric fractures are a public health issue due to the aging of the population. Treatment aims to reduce their related morbidity and mortality and to allow an early return to independence. Post-operative anemia is associated with poorer functional recovery and an increased mortality rate. The aim of this study was to assess whether minimally invasive side plate fixation (Minimal Invasive Screw System, MISS™) resulted in reduced perioperative bleeding compared with conventional fixation (Pertrochanteric Hip Screw, PHS™).

HYPOTHESIS: We hypothesized that minimally invasive side plate fixation (MISS) would result in reduced perioperative bleeding compared with conventional fixation (PHS).

PATIENTS AND METHODS: We conducted an open randomized controlled trial with blinded assessment of the primary outcome. Inclusion criteria were patients aged over 65 years with isolated reducible trochanteric fracture. The 2 surgical implants were of the same shape, the only difference between them being the locking mode of the femoral neck screw on the plate of the MISS device, allowing a percutaneous approach. Primary outcome was perioperative bleeding evaluated with Mercuriali’s formula. Secondary outcomes included operating time, scar length, length of hospital stay, radiological criteria such as quality of fracture reduction, implant positioning and bone healing, and complications and functional recovery compared between the 2 groups.

RESULTS: One hundred eight patients met the inclusion criteria and were randomized to receive either PHS (n = 54) or MISS (n = 54). Osteosynthesis with MISS significatively reduced perioperative bleeding (median 243 ml, interquartile range [152-410] vs 334 ml [247-430] with PHS (p = 0.0299)), operating time (65 min [57-73] vs 79 min [66-89] (p = 0.0002)) and scar length after 45 days (7 cm [5-8] vs 14 cm [12-15] (p < 0.0001)). There was no statistically significant difference between groups in postoperative complications, revision surgery or serious adverse events.

CONCLUSION: Compared with PHS, MISS reduced operating time, perioperative bleeding and scar length with no observed functional difference.

LEVEL OF EVIDENCE: I.

PMID:37474020 | DOI:10.1016/j.otsr.2023.103661

Exp Eye Res. 2023 Jul 18:109592. doi: 10.1016/j.exer.2023.109592. Online ahead of print.

ABSTRACT

Understanding the metabolic dysfunctions and underlying complex pathological mechanisms of neurodegeneration in glaucoma could help discover disease pathways, identify novel biomarkers, and rationalize newer therapeutics. Therefore, we aimed to investigate the local metabolomic alterations in the aqueous humor and plasma of primary glaucomatous patients. This study cohort comprised primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and cataract control groups. Aqueous humor and plasma samples were collected from patients undergoing trabeculectomy or cataract surgery and subjected to high-resolution mass spectrometry (HRMS) analysis. Spectral information was processed, and the acquired data were subjected to uni-variate as well as multi-variate statistical analyses using MetaboAnalyst ver5.0. To further understand the localized metabolic abnormalities in glaucoma, metabolites affected in aqueous humor were distinguished from metabolites altered in plasma in this study. Nine and twelve metabolites were found to be significantly altered (p < 0.05, variable importance of projection >1 and log₂ fold change ≥0.58/≤ -0.58) in the aqueous humor of PACG and POAG patients, respectively. The galactose and amino acid metabolic pathways were locally affected in the PACG and POAG groups, respectively. Based on the observation of the previous findings, gene expression profiles of trace amine-associated receptor-1 (TAAR-1) were studied in rat ocular tissues. The pharmacodynamics of TAAR-1 were explored in rabbits using topical administration of its agonist, β-phenyl-ethylamine (β-PEA). TAAR-1 was expressed in the rat’s iris-ciliary body, optic nerve, lens, and cornea. β-PEA elicited a mydriatic response in rabbit eyes without altering intraocular pressure. Targeted analysis of β-PEA levels in the aqueous humor of POAG patients showed an insignificant elevation. This study provides new insights regarding alterations in both localized and systemic metabolites in primary glaucomatous patients. This study also demonstrated the propensity of β-PEA to cause an adrenergic response through the TAAR-1 pathway.

PMID:37474016 | DOI:10.1016/j.exer.2023.109592

Exp Eye Res. 2023 Jul 18:109590. doi: 10.1016/j.exer.2023.109590. Online ahead of print.

ABSTRACT

Animal models of choroidal neovascularization (CNV) are extensively used in translational studies of CNV formation and to evaluate angiostatic treatment strategies. However, the current paucity of large animal models compared with rodent models constitutes a knowledge gap regarding the clinical translation of findings. Ocular anatomical and physiological similarities to humans suggest the pig as a relevant model animal. Thus, a systematic survey of porcine CNV models was performed to identify pertinent model parameters and suggest avenues for model standardization and optimization. A systematic search was performed in PubMed and EMBASE on November 28, 2022 for porcine models of CNV. Following inclusion by two investigators, data from the articles were extracted according to a predefined protocol. A total of 14 articles, representing 19 independent porcine CNV models were included. The included models were almost equally divided between laser-induced (53%) and surgically-induced (47%) models. Different specified breeds of domestic pigs (71%) were most commonly used in the studies. All studies used normal animals. Female pigs were reported used in 43% of the studies, while 43% did not report on sex of the animals. Younger pigs were typically used. The surgical models reported consistent CNV induction following mechanical Bruch’s membrane rupture. The laser models used variants of the infrared diode laser (40%) or the frequency-doubled Nd:YAG laser (50%). Both lasers enabled successful CNV induction with reported induction rates ranging from 60 to 100%. Collateral damage to the neuroretina was reported for the infrared diode laser. CNV evaluation varied across studies with fluorescein angiography (50%) as the most used in vivo method and retinal sections (71%) as the most used ex vivo method. In interventional studies, quantification of lesions was in general performed between 7 and 14 days. The field of porcine CNV models is relatively small and heterogeneous and almost equally divided between surgically-induced and laser-induced models. Both methods have allowed successful modeling of CNV formation with induction rates comparable to those of non-human primates. However, the field would benefit from standardization of model parameters and reporting. This includes laser parameters and validation of CNV formation as well as methods of CNV evaluation and statistical analysis.

PMID:37474015 | DOI:10.1016/j.exer.2023.109590

Mod Pathol. 2023 Jul 18:100285. doi: 10.1016/j.modpat.2023.100285. Online ahead of print.

ABSTRACT

We have developed an artificial intelligence (AI)-based digital pathology model for the evaluation of histologic features related to eosinophilic esophagitis (EoE). In this study, we evaluate the performance of our AI model in a cohort of pediatric and adult patients for histologic features included in the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). We collected a total of 203 esophageal biopsies from patients with mucosal eosinophilia of any degree (91 adults, 112 pediatric patients) and 10 normal controls from a prospectively maintained database. All cases were assessed by a specialized gastrointestinal (GI) pathologist for features in the EoEHSS at the time of original diagnosis and re-scored by a central GI pathologist. We have subsequently analyzed whole-slide image digital slides using a supervised AI model operating in a cloud-based, deep-learning artificial intelligence platform (Aiforia Technologies, Helsinki, Finland) for peak eosinophil count (PEC) and several histopathologic features in the EoEHSS. The correlation and inter-observer agreement between the AI model and pathologists (r_s=0.89 and ICC=0.87 vs. original pathologist [OP]; r_s =0.91 and ICC=0.83 vs. central pathologist [CP]) was similar to the correlation and inter-observer agreement between pathologists for PEC (r_s=0.88 and ICC=0.91) and broadly similar for most other histologic features in the EoEHSS. The AI model PEC also accurately identified >15 eosinophils/HPF by the OP (AUC [area under the curve]=0.98) and CP (AUC=0.98) and had similar AUCs for the presence of EoE-related endoscopic features than pathologists’ assessment. Average eosinophils per epithelial unit area had similar performance compared to AI HPF-based analysis. Our newly developed AI model can accurately identify, quantify, and score several of the main histopathologic features in the EoE spectrum, with agreement regarding EoEHSS scoring, which was similar to that seen among GI pathologists.

PMID:37474003 | DOI:10.1016/j.modpat.2023.100285

J Thorac Cardiovasc Surg. 2023 Jul 18:S0022-5223(23)00612-8. doi: 10.1016/j.jtcvs.2023.07.008. Online ahead of print.

ABSTRACT

OBJECTIVE: We have recently reported the primary results of CALGB 140503 (Alliance), a randomized trial in patients with peripheral cT1aN0 NSCLC (AJCC 7^th) treated with either lobar (LR) or sublobar resection (SLR). Here we report differences in disease-free survival (DFS), overall survival (OS) and lung cancer specific survival (LCSS) between LR, segmental (SR) and wedge resections (WR). We also report differences between WR and SR in surgical margins, rates of locoregional recurrence (LRR) and expiratory flow rates at 6 months postoperatively.

METHODS: Between 6/2007 and 3/2017, 697 patients were randomized to LR (357) or SLR (340) stratified by clinical tumor size, histology and smoking history. Ten patients were converted from SLR to LR and 5 from LR to SLR. Survival end points were estimated by the Kaplan-Meier estimator and tested by the stratified Log rank test. Kruskal-Wallis testing was used to compare margins and FEV1 changes between groups; and a Chi-square test was used to test the association between recurrence and groups.

RESULTS: A total of 362 patients had LR, 131 had SR and 204 had WR. Basic demographic and clinical and pathological characteristics were similar between all three groups. Five-year DFS was 64.7% after LR [95% CI; 59.6-70.1%], 63.8% after SR [ 95% C; 55.6 – 73.2%] and 62.5% after WR [95% CI; 55.8 – 69.9%] (Log rank, p = 0.888). Five-year OS was 78.7% after LR, 81.9% after SR and 79.7% after WR (Log rank, p = 0.873). Five-year LCSS was 86.8% after LR, 89.2% after SR and 89.7% after WR (Log rank, p = 0.903). LRR occurred in 12% after SR and 14% after WR (p=0.295). At 6 months postoperatively, the median reduction in % FEV1 was 5% after WR and 3% after SR (p=0.930) CONCLUSIONS: In this large, randomized trial, LR, SR and WR were associated with similar survival outcomes. Although LRR was numerically higher after WR compared to SR, the difference was not clinically meaningful statistically significant. There was no significant difference in the reduction of FEV1 between the SR and WR groups.

PMID:37473998 | DOI:10.1016/j.jtcvs.2023.07.008

Neuroimage Clin. 2023 Jul 11;39:103471. doi: 10.1016/j.nicl.2023.103471. Online ahead of print.

ABSTRACT

BACKGROUND: Using multi-block methods we combined multimodal neuroimaging metrics of thalamic morphology, thalamic white matter tract diffusion metrics, and cortical thickness to examine changes in behavioural variant frontotemporal dementia. (bvFTD).

METHOD: Twenty-three patients with sporadic bvFTD and 24 healthy controls underwent structural and diffusion MRI scans. Clinical severity was assessed using the Clinical Dementia Rating scale and behavioural severity using the Frontal Behaviour Inventory by patient caregivers. Thalamic volumes were manually segmented. Anterior and posterior thalamic radiation fractional anisotropy and mean diffusivity were extracted using Tract-Based Spatial Statistics. Finally, cortical thickness was assessed using Freesurfer. We used shape analyses, diffusion measures, and cortical thickness as features in sparse multi-block partial least squares (PLS) discriminatory analyses to classify participants within bvFTD or healthy control groups. Sparsity was tuned with five-fold cross-validation repeated 10 times. Final model fit was assessed using permutation testing. Additionally, sparse multi-block PLS was used to examine associations between imaging features and measures of dementia severity.

RESULTS: Bilateral anterior-dorsal thalamic atrophy, reduction in mean diffusivity of thalamic projections, and frontotemporal cortical thinning, were the main features predicting bvFTD group membership. The model had a sensitivity of 96%, specificity of 68%, and was statistically significant using permutation testing (p = 0.012). For measures of dementia severity, we found similar involvement of regional thalamic and cortical areas as in discrimination analyses, although more extensive thalamo-cortical white matter metric changes.

CONCLUSIONS: Using multimodal neuroimaging, we demonstrate combined structural network dysfunction of anterior cortical regions, cortical-thalamic projections, and anterior thalamic regions in sporadic bvFTD.

PMID:37473493 | DOI:10.1016/j.nicl.2023.103471

Psychiatry Res. 2023 Jul 11;326:115343. doi: 10.1016/j.psychres.2023.115343. Online ahead of print.

ABSTRACT

Anxiety disorders are a group of prevalent and heritable neuropsychiatric diseases. We previously conducted a genome-wide association study (GWAS) which identified genomic loci associated with anxiety; however, the biological consequences underlying the genetic associations are largely unknown. Integrating GWAS and functional genomic data may improve our understanding of the genetic effects on intermediate molecular phenotypes such as gene expression. This can provide an opportunity for the discovery of drug targets for anxiety via drug repurposing. We used the GWAS summary statistics to determine putative causal genes for anxiety using MAGMA and colocalization analyses. A transcriptome-wide association study was conducted to identify genes with differential genetically regulated levels of gene expression in human brain tissue. The genes were integrated with a large drug-gene expression database (Connectivity Map), discovering compounds that are predicted to “normalise” anxiety-associated expression changes. The study identified 64 putative causal genes associated with anxiety (35 genes upregulated; 29 genes downregulated). Drug mechanisms adrenergic receptor agonists, sigma receptor agonists, and glutamate receptor agonists gene targets were enriched in anxiety-associated genetic signal and exhibited an opposing effect on the anxiety-associated gene expression signature. The significance of the project demonstrated genetic links for novel drug candidates to potentially advance anxiety therapeutics.

PMID:37473490 | DOI:10.1016/j.psychres.2023.115343

Clin Neurol Neurosurg. 2023 Jul 10;232:107887. doi: 10.1016/j.clineuro.2023.107887. Online ahead of print.

ABSTRACT

OBJECTIVE: To gauge resident knowledge in the socioeconomic aspects of neurosurgery and assess the efficacy of an asynchronous, longitudinal, web-based, socioeconomics educational program tailored for neurosurgery residents.

METHODS: Trainees completed a 20-question pre- and post-intervention knowledge examination including four educational categories: billing/coding, procedure-specific concepts, material costs, and operating room protocols. Structured data from 12 index cranial neurosurgical operations were organized into 5 online, case-based modules sent to residents within a single training program via weekly e-mail. Content from each educational category was integrated into the weekly modules for resident review.

RESULTS: Twenty-seven neurosurgical residents completed the survey. Overall, there was no statistically significant difference between pre- vs post-intervention resident knowledge of billing/coding (79.2 % vs 88.2 %, p = 0.33), procedure-specific concepts (34.3 % vs 39.2 %, p = 0.11), material costs (31.7 % vs 21.6 %, p = 0.75), or operating room protocols (51.7 % vs 35.3 %, p = 0.61). However, respondents’ accuracy increased significantly by 40.8 % on questions containing content presented more than 3 times during the 5-week study period, compared to an increased accuracy of only 2.2 % on questions containing content presented less often during the same time period (p = 0.05).

CONCLUSIONS: Baseline resident knowledge in socioeconomic aspects of neurosurgery is relatively lacking outside of billing/coding. Our socioeconomic educational intervention demonstrates some promise in improving socioeconomic knowledge among neurosurgery trainees, particularly when content is presented frequently. This decentralized, web-based approach to resident education may serve as a future model for self-driven learning initiatives among neurosurgical residents with minimal disruption to existing workflows.

PMID:37473488 | DOI:10.1016/j.clineuro.2023.107887

Clin Neurol Neurosurg. 2023 Jul 16;232:107898. doi: 10.1016/j.clineuro.2023.107898. Online ahead of print.

ABSTRACT

OBJECTIVE: It is unknown whether adjunctive intra-arterial thrombolysis (IAT) during mechanical thrombectomy (MT) improves outcomes in patients with large vessel occlusion (LVO) stroke. This systematic review and meta-analysis aimed to compare the safety and efficacy of MT with and without IAT for the treatment of LVO stroke.

METHODS: A systematic literature search of PubMed, Embase, and the Cochrane Library was conducted to identify studies that compared rates of 3-month functional independence (modified Rankin Scale score 0-2), successful revascularization, symptomatic intracranial hemorrhage, and 3-month mortality for MT+IAT and MT alone. Meta-analyses were performed using random effects models, and effect sizes were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was assessed with Cochran’s Q test and I² statistic.

RESULTS: Twelve studies met eligibility criteria, comprising one randomized controlled trial and 11 observational cohort studies involving 2584 patients. Compared to MT alone, MT+IAT had a 43% higher odds of 3-month functional independence (OR 1.43, 95% CI 1.11-1.83; I² =21%) and a 23% decrease in odds for 3-month mortality (OR 0.77, 95% CI 0.60-0.99; I² =0%). There were no differences in successful revascularization (OR 1.39, 95% CI 0.89-2.17; I² =57%) or symptomatic intracranial hemorrhage (OR 0.87, 95% CI 0.56-1.35; I² =6%) between the two groups.

CONCLUSIONS: The present study has demonstrated that, compared with MT alone, the use of adjunct IAT during MT in patients with LVO stroke resulted in better functional outcomes and lower mortality.

PMID:37473487 | DOI:10.1016/j.clineuro.2023.107898