Category: Nevin Manimala

Radiother Oncol. 2024 Apr 6:110271. doi: 10.1016/j.radonc.2024.110271. Online ahead of print.

ABSTRACT

PURPOSE: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities.

MATERIALS AND METHODS: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/β = 2 for brain tissue and α/β = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis.

RESULTS: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively).

CONCLUSIONS: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice.

PMID:38588920 | DOI:10.1016/j.radonc.2024.110271

Free Radic Biol Med. 2024 Apr 6:S0891-5849(24)00382-4. doi: 10.1016/j.freeradbiomed.2024.04.211. Online ahead of print.

ABSTRACT

DNA repair is essential to maintain genomic integrity and may affect colorectal cancer (CRC) patients’ risk of secondary cancers, treatment efficiency, and susceptibility to various comorbidities. Bioactive compounds identified in plant food have the potential to modulate DNA repair mechanisms, but there is limited evidence of how dietary factors may affect DNA repair activity in CRC patients in remission after surgery. The aim of this study was to investigate the effect of a 6 months personalized intensive dietary intervention on DNA repair activity in post-surgery CRC patients (stage I-III). The present study included patients from the randomized controlled trial CRC-NORDIET, enrolled 2-9 months after surgery. The intervention group received an intensive dietary intervention emphasizing a prudent diet with specific plant-based foods suggested to dampen inflammation and oxidative stress, while the control group received only standard care advice. The comet-based in vitro repair assay was applied to assess DNA repair activity, specifically base excision repair (BER), in peripheral blood mononuclear cells (PBMCs). Statistical analyses were conducted using gamma generalized linear mixed models (Gamma GLMM). A total of 138 CRC patients were included, 72 from the intervention group and 66 from the control group. The BER activity in the intervention group did not change significantly compared to the control group. Our findings revealed a substantial range in both inter- and intra-individual levels of BER. In conclusion, the results do not support an effect of dietary intervention on BER activity in post-surgery CRC patients during a 6-month intervention period.

PMID:38588903 | DOI:10.1016/j.freeradbiomed.2024.04.211

Mol Biochem Parasitol. 2024 Apr 6:111618. doi: 10.1016/j.molbiopara.2024.111618. Online ahead of print.

ABSTRACT

Trypanosoma cruzi is a parasite with a high capacity to adapt to the host. Animal models have already demonstrated that the tropism of this parasite occurs not only in cardiac/digestive tissues but also in adipose tissue (AT). That said, the consequences ofT. cruziinfection for AT and the implications of treatment with Benzonidazole in this tissue are under discussion. Here, we tested the hypothesis that T. cruzi infection in adipose tissue upon treatment with Benzonidazole (Bz) and the interaction of mononuclear immune cells (PBMC) influences the relative expression of ACAT1, FASN, and PNPLA2 genes. Thus, stem cells derived from adipose tissue (ADSC) after adipogenic differentiation were indirectly cultivated with PBMC after infection with the T. cruzi Y strain and treatment with Bz. We use the TcSAT-IAM system and RT-qPCR to evaluate the parasite load and the relative quantification (ΔCt) of the ACAT1, FASN, and PNPLA2 genes. Our results demonstrate that treatment with Bz did not reduce adipocyte infection in the presence (p-value: 0.5796) or absence (p-value: 0.1854) of cultivation with PBMC. In addition, even though there is no statistical difference when compared to the control group (AT), T. cruzi induces the FASN expression (Rq: 14.00). However, treatment with Bz in AT suggests the increases of PNPLA2 expression levels (Rq: 12.58), even in the absence of T. cruzi infection. During indirect cultivation with PBMC, T. cruzi smooths the expression of PNPLA2 (Rq: 0.824) and instigates the expression of ACAT1 (Rq: 1.632) and FASN (Rq: 1.394). Furthermore, the treatment with Bz during infection induces PNPLA2 expression (Rq: 1.871), maintaining FASN expression levels (Rq: 1.334). Given this, our results indicate that treatment with Benzonidazole did not decrease T. cruzi infection in adipose tissue. However, treating the adipocyte cells with Bz during the interaction with PBMC cells influences the lipid pathways scenario, inducing lipolytic metabolism through the expression of PNPLA2.

PMID:38588892 | DOI:10.1016/j.molbiopara.2024.111618

J Foot Ankle Surg. 2024 Apr 6:S1067-2516(24)00068-1. doi: 10.1053/j.jfas.2024.03.003. Online ahead of print.

ABSTRACT

Residual osteomyelitis is a frequent problem following surgical intervention for diabetic foot infection. The current Infectious Disease Society of America guidelines recommend 4-6 weeks of initial intravenous antibiotics for treatment of residual osteomyelitis. However, recent literature suggests oral antibiotic therapy is not inferior to intravenous therapy. The primary aim of this study was to evaluate treatment success in 128 patients receiving oral versus intravenous antibiotics for residual osteomyelitis in the diabetic foot after amputation at a Level 1 academic medical trauma center. Treatment success was defined as completion of at least 4 weeks antibiotic therapy, complete surgical wound healing, and no residual infection requiring further debridement or amputation within one year of the initial surgery. Patients with peripheral arterial disease were excluded. A retrospective chart review was performed, and we found no statistically significant difference in treatment success between these two groups (p=0.2766). Median time to healing for oral antibiotic treatment was 3.17 months compared to 4.06 months for intravenous treatment (p=0.1045). Furthermore, there was no significant difference in group demographics or comorbidities, aside from more patients in the intravenous group having coronary artery disease (p=0.0416). Type of closure and type of microbial infection was also not associated with a difference in outcomes between the two treatment arms. The results of the present study suggest oral antibiotics for treatment of residual osteomyelitis are not inferior to intravenous therapy and may be more efficacious for certain patients regarding cost and ease of administration. LEVEL OF CLINICAL EVIDENCE: : 3.

PMID:38588891 | DOI:10.1053/j.jfas.2024.03.003

Mod Pathol. 2024 Apr 6:100485. doi: 10.1016/j.modpat.2024.100485. Online ahead of print.

ABSTRACT

Several studies have developed various artificial intelligence (AI) models for immunohistochemical analysis of programmed death ligand 1 (PD-L1) in patients with non-small cell lung carcinoma; however, none have focused on specific ways by which AI-assisted systems could help pathologists determine the tumor proportion score (TPS). Herein, we developed an AI model to calculate the TPS of the PD-L1 22C3 assay and evaluated whether and how this AI-assisted system could help pathologists determine the TPS and analyze how AI-assisted systems could affect pathologists’ assessment accuracy. We assessed the four methods of the AI-assisted system: 1) and 2) pathologists first assessed and then referred to automated AI scoring results (1, positive tumor cell percentage; 2, positive tumor cell percentage and visualized overlay image) for a final confirmation, and 3) and 4) pathologists referred to the automated AI scoring results (3, positive tumor cell percentage; 4, positive tumor cell percentage and visualized overlay image) while determining TPS. Mixed model analysis was used to calculate the odds ratios (ORs) with 95% confidence intervals for AI-assisted TPS 1) to 4) compared with pathologists’ scoring. For all 584 samples of tissue microarray, the OR for AI-assisted TPS 1) to 4) was 0.94-1.07 and not statistically significant. Of them, we found 332 cases of discordant cases, on which the pathologists’ judgments were inconsistent; the ORs for AI-assisted TPS 1), 2), 3), and 4) were 1.28 (1.06-1.54, p = 0.012), 1.29 (1.06-1.55, p = 0.010), 1.28 (1.06-1.54, p = 0.012), and 1.29 (1.06-1.55, p = 0.010), respectively, which were statistically significant. For discordant cases, the OR for each AI-assisted TPS compared with the others was 0.99-1.01 and not statistically significant. This study emphasized the usefulness of the AI-assisted system for cases wherein pathologists had difficulty determining the PD-L1 TPS.

PMID:38588885 | DOI:10.1016/j.modpat.2024.100485

Mod Pathol. 2024 Apr 6:100486. doi: 10.1016/j.modpat.2024.100486. Online ahead of print.

ABSTRACT

The role of Artificial intelligence (AI) in pathology is one that offers many exciting new possibilities for improving patient care. This study contributes to this development by identifying the viability of AICyte Assistive System for cervical screening, and to investigate the utility of the system in assisting with workflow and diagnostic capability. In this study, a novel scanner was developed using a Ruiqian WSI-2400, trademarked AICyte Assistive system, to create AI-generated gallery of the most diagnostically relevant images, objects of interest (OOI), and provide categorical assessment, according to Bethesda category, for cervical ThinPrep Pap slides. For validation purposes, two pathologists reviewed OOIs from 32,451 cases of ThinPrep Paps independently, and their interpretations were correlated with the original ThinPrep interpretations (OTPI). The analysis was focused on the comparison of reporting rates, correlation between cytological results and histological follow-up findings, and the assessment of independent AICyte screening utility. Pathologists using the AICyte system had a mean reading time of 55.14 seconds for the first 3,000 cases trending down to 12.90 seconds in the last 6,000 cases. Overall average reading time was 22.23 seconds per case as compared to a manual reading time approximation of 180 seconds. Usage of AICyte compared to OTPI had similar sensitivity (97.89% vs 97.89%) and a statistically significant increase in specificity (16.19% vs 6.77%). When AICyte was run alone at a 50% negative cut-off value, it was able to read slides with a sensitivity of 99.30% and specificity of 9.87%. When AICyte was run independently at this cut-off value, no sole case of HSIL/SCC squamous lesion was missed. AICyte can provide a potential tool to help pathologists in both diagnostic capability and efficiency, which remained reliable as compared to baseline standard. Also unique for AICyte is the development of a negative cutoff value for which AICyte can categorize cases as “not needed for review” to triage cases and lower pathologist workload. This is the largest case number study that pathologists reviewed OOI with AI assistive system. The study demonstrates that AI assistive system can be broadly applied for cervical cancer screening.

PMID:38588882 | DOI:10.1016/j.modpat.2024.100486

J Ethn Subst Abuse. 2024 Apr 8:1-13. doi: 10.1080/15332640.2024.2336495. Online ahead of print.

ABSTRACT

Drug addiction remains one of the most complex social problems worldwide that has yet to be resolved. In Malaysia, abuse of various types of drugs has been reported which warrants the government to take immediate strategies in managing drug addicts. Despite implementing various strategies to treat drug addiction, statistics show the number of relapses continues to skyrocket over the years. This calls for urgent attention to improve the effectiveness of substance abuse treatment services in Malaysia. Moreover, emerging evidence shows a change in trend in the type of drug being abused. This factor could potentially contribute to the ineffectiveness of the strategies employed in the treatment of substance abuse. Therefore, this review provides an overview of the major types of drugs commonly abused in Malaysia. Additionally, in an effort to search for ways to improve the effectiveness of substance abuse treatment services, we identified the public institutions responsible for managing drug addicts in Malaysia and discussed the therapeutic programs offered at the institutions. Review findings support the need for future research on the effectiveness of these therapeutic programs and recommend the implementation of evidence-based programs to improve the effectiveness of substance abuse treatments in Malaysia.

PMID:38588590 | DOI:10.1080/15332640.2024.2336495

Interdiscip Cardiovasc Thorac Surg. 2024 Apr 8:ivae056. doi: 10.1093/icvts/ivae056. Online ahead of print.

ABSTRACT

OBJECTIVE: The premise of this retrospective study was to evaluate the intraoperative use of closed incision negative pressure therapy (ciNPT) to help reduce the incidence of postoperative sternal wound infections (SWI) in multimorbid patients with an elevated risk of developing an SWI post cardiac surgery versus a cohort that received standard of care dressings.

METHODS: Data of all adult patients were collected from each cardiothoracic surgery units across three hospitals in the United Kingdom. High-risk patients had two or more recognised risk factors. Fisher’s exact test (two-tailed) and unpaired t-test helped analyse categorical and continuous data. Propensity matching was performed to compare the two groups.

RESULTS: A total of 5,288 patients who had cardiac surgery were included. Propensity matching led to 766 matched cases. There were significantly fewer sternal wound infections in the ciNPT group (43 [5.6%] versus 119 [15.5%] cases; p = 0.0001), as well as fewer deep sternal wound infections (14 [1.8%] versus 31 [4.0%] cases; p = 0.0149) and superficial sternal wound infections (29 [3.8%] versus 88 [11.4%] cases; p = 0.0001). A higher mean length of stay in the ciNPT group was statistically significant (11.23±13 versus 9.66±10 days; p = 0.0083) as well as a significantly higher mean logistic EuroSCORE (11.143±13 versus 8.094±11; p = 0.0001). A statistically significant higher readmission to intensive care due to sternal wound infection was noted for the Control (16 [2.08%] versus 3 [0.39%] readmissions; p = 0.0042).

CONCLUSION: ciNPT appears to be an effective intervention to help reduce the incidence of sternal wound infection in high-risk individuals undergoing cardiac surgery.

PMID:38588571 | DOI:10.1093/icvts/ivae056

Rheumatology (Oxford). 2024 Apr 8:keae217. doi: 10.1093/rheumatology/keae217. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the clinical features of Chinese patients with hydroxychloroquine (HCQ)-induced pigmentation and analyze the potential risk factors associated with HCQ-induced pigmentation.

METHODS: A cross-sectional study was conducted over a duration of 7 months, during which patients who had received HCQ treatment for >6 months were included. Data was collected through a structured questionnaire that encompassed demographic and geographic characteristics, information on HCQ and concomitant medication usage, sun exposure characteristics, and hyperpigmentation-related characteristics. Univariate and multivariate analyses were employed to calculate the statistical association between HCQ-induced pigmentation and multiple variables.

RESULTS: Out of 316 patients, 83 (26.3%) patients presented hyperpigmentation during HCQ treatment. Hyperpigmentation presented after a median duration of HCQ treatment of 12 months (interquartile range, 6.0 months-30.0 months) with a median cumulative dose of 108 g of HCQ (interquartile range, 36-288 g). The most frequently affected sites of pigmentation were the face (60.2%), lower limbs (36.1%), and hands (20.5%). There was a linear decrease in the incidence of pigmentation with increasing daily sun exposure time (p= 0.030). In the multivariate analysis, variables (cumulative HCQ dose and daily sun exposure time) were included in the final models. The results revealed an independent correlation between HCQ-induced pigmentation and daily sun exposure exceeding 1 h (OR: 0.431; 95%CI: 0.208-0.892; p= 0.023).

CONCLUSIONS: The occurrence of HCQ-induced pigmentation is not uncommon, with an incidence rate of 26.3%. Daily sun exposure time exhibited a protective effect against HCQ-induced pigmentation.

PMID:38588566 | DOI:10.1093/rheumatology/keae217