Tag: nevin manimala

Transplant Cell Ther. 2024 Mar 21:S2666-6367(24)00292-6. doi: 10.1016/j.jtct.2024.03.019. Online ahead of print.

ABSTRACT

INTRODUCTION: Transplant-associated thrombotic microangiopathy (TA-TMA) is associated with high morbidity and mortality. Although with the introduction of eculizumab the survival has significantly improved, there is still a need for improvement, especially in high-risk patients.

OBJECTIVES: This study aims to describe the results obtained with eculizumab in a pediatric cohort with the attempt to define which risk factors could determine the response to treatment.

METHODS: We designed a national multicentre retrospective study, where children treated with eculizumab for high-risk TA-TMA were included.

RESULTS: Twenty-nine patients were included after a first (n=28) or a second allogeneic hematopoietic stem cell transplantation (HSCT) (n=1) for malignant (n=17) or non-malignant diseases (n=12). Median time from HSCT to TA-TMA diagnosis was 154 days (IQR 103-263). Eleven patients (38%) were initially diagnosed of low – intermediate risk TA-TMA and progressed to high-risk TA-TMA (hrTA-TMA), with a median time of 4 days (IQR 1 – 33). SC5b-9 was increased in 90% of 20 patients where measured. Renal (n=12), pulmonary (n=1) and intestinal (n=1) biopsy confirmed the diagnosis in 12/14 patients (85%). Seventeen patients (58%) presented extrarenal involvement with serositis (n=13, 44,8%), pulmonary (n=12, 41,4%), gastrointestinal (n=8, 27,6%), cardiovascular (n=7, 24,1%) or central nervous system (CNS) (n=2, 6,9%) involvement. Median time from hrTA-TMA diagnosis to the initiation of eculizumab was 7 days (IQR 1-18). Overall, 19 patients (65.5%) responded to eculizumab of whom 17 (58,6%) presented complete response and 2 (6.9%) achieved partial response. The remaining 10 patients (34.5%) did not present any type of response. The TA-TMA ORR was 27.59 % (95% CI 14.87 – 47.66), 55.17% (95% CI 38.43 – 73.48) and 62.07% (95% CI 45.10 – 79.13%) at 1, 3 and 6 months post eculizumab initiation, respectively. In the multivariate analysis the pulmonary involvement decreased the probability of response (HR 0.18, p-value 0.0298). The 1-year OS was 55.2% (95% CI: 35.6-71.0) for the whole cohort and 83.3% (95% CI: 56.7-94.3) for patients who responded to eculizumab. The presence of pulmonary (HR 14.93, p-value 0.0043) and CNS involvement (HR 8.63, p-value 0.0497) presented a statistically significant decrease in survival.

CONCLUSION: We found that patients diagnosed of hrTA-TMA with pulmonary involvement presented a poor response to eculizumab and patients with pulmonary and CNS involvement a significant decreased in survival. With these results, we hypothesize that using eculizumab at an early stage of the disease and before organ damage is established, the response and therefore the survival might significantly improve.

PMID:38521410 | DOI:10.1016/j.jtct.2024.03.019

J Cardiovasc Magn Reson. 2024 Mar 21:101039. doi: 10.1016/j.jocmr.2024.101039. Online ahead of print.

ABSTRACT

BACKGROUND: MRI is an important imaging modality for the assessment and management of adult patients with congenital heart disease (CHD). However, conventional techniques for 3D whole-heart acquisition involve long and unpredictable scan times and methods that accelerate scans via k-space undersampling often rely on long iterative reconstructions. Deep-learning-based reconstruction methods have recently attracted much interest due to their capacity to provide fast reconstructions whilst often outperforming existing state-of-the-art methods. In this study, we sought to adapt and validate a non-rigid motion-corrected model-based deep-learning (MoCo-MoDL) reconstruction framework for 3D whole-heart MRI in a CHD patient cohort.

METHODS: The previously proposed deep-learning reconstruction framework MoCo-MoDL, which incorporates a non-rigid motion-estimation network and a denoising regularisation network within an unrolled iterative reconstruction, was trained in an end-to-end manner using 39 CHD patient datasets. Once trained, the framework was evaluated in 8 CHD patient datasets acquired with seven-fold prospective undersampling. Reconstruction quality was compared with the state-of-the-art non-rigid motion-corrected patch-based low-rank reconstruction method (NR-PROST) and against reference images (acquired with three-or-four-fold undersampling and reconstructed with NR-PROST).

RESULTS: Seven-fold undersampled scan times were 2.1 ± 0.3 minutes and reconstruction times were ~ 30 seconds, approximately 240 times faster than an NR-PROST reconstruction. Image quality comparable to the reference images was achieved using the proposed MoCo-MoDL framework, with no statistically significant differences found in any of the assessed quantitative or qualitative image quality measures. Additionally, expert image quality scores indicated the MoCo-MoDL reconstructions were consistently of a higher quality than the NR-PROST reconstructions of the same data, with the differences in 12 of the 22 scores measured for individual vascular structures found to be statistically significant.

CONCLUSION: The MoCo-MoDL framework was applied to an adult CHD patient cohort, achieving good quality 3D whole-heart images from ~ 2-minute scans with reconstruction times of ~ 30 seconds.

PMID:38521391 | DOI:10.1016/j.jocmr.2024.101039

Asia Pac J Ophthalmol (Phila). 2024 Mar 21:100052. doi: 10.1016/j.apjo.2024.100052. Online ahead of print.

ABSTRACT

IMPORTANCE: Ocular surface squamous neoplasia (OSSN) is a spectrum of malignancies that generally includes conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). OSSN can be treated with topical therapies including interferon α-2b (IFN), mitomycin C (MMC), or 5-fluorouracil 1% (5FU). Recently, due to unavailability of IFN and toxicity associated with MMC, therapy has shifted towards 5FU.

OBJECTIVE: Herein, we compare the use of 5FU 1% as a primary versus (vs) secondary treatment regimen in eyes with moderate to extensive OSSN.

DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study of 73 consecutive patients with unilateral moderate to extensive OSSN treated at a single tertiary ocular oncology center from 2016 to 2023. Mean follow up time was 478.2 days overall, with 283.0 days for primary 5FU group and 860.3 days for secondary 5FU group.

INTERVENTION: Topical 5FU 1% 4 times daily for 2 weeks with option for 2-weekly extension until tumor control, either as primary treatment or as secondary treatment to surgical resection, topical IFN or topical MMC, or cryotherapy.

MAIN OUTCOMES: Outcome measures included tumor response, need for additional surgery, complications, and visual outcomes.

RESULTS: A comparison (primary vs secondary treatment) revealed no difference in mean tumor basal dimension (19.6 vs 17.2mm, P = 0.46), thickness (3.7 vs 3.4mm, P = 0.64), or tumor extent (4.4 vs 4.5 clock hours, P = 0.92). The primary treatment group showed greater complete tumor control (77% vs 38%, P = 0.04). Multivariable analysis comparison (primary vs secondary treatment) showed primary treatment more likely to achieve complete tumor control (P = 0.01). There was no difference in the complication rate from 5FU treatment between the groups. There was no difference in visual outcome, and no tumor-related metastasis (0%) or death (0%).

CONCLUSION AND RELEVANCE: Topical 5FU 1% is efficacious and safe as a primary or secondary treatment for moderate to extensive OSSN. Tumors treated with primary 5FU 1% demonstrated more complete resolution. In patients with moderate to extensive OSSN, primary treatment with topical 5FU 1% may be warranted.

PMID:38521390 | DOI:10.1016/j.apjo.2024.100052

Anim Biotechnol. 2024 Nov;35(1):2331179. doi: 10.1080/10495398.2024.2331179. Epub 2024 Mar 22.

ABSTRACT

Despite the significant threat of heat stress to livestock animals, only a few studies have considered the potential relationship between broiler chickens and their microbiota. Therefore, this study examined microbial modifications, transcriptional changes and host-microbiome interactions using a predicted metabolome data-based approach to understand the impact of heat stress on poultry. After the analysis, the host functional enrichment analysis revealed that pathways related to lipid and protein metabolism were elevated under heat stress conditions. In contrast, pathways related to the cell cycle were suppressed under normal environmental temperatures. In line with the transcriptome analysis, the microbial analysis results indicate that taxonomic changes affect lipid degradation. Heat stress engendered statistically significant difference in the abundance of 11 microorganisms, including Bacteroides and Peptostreptococcacea. Together, integrative approach analysis suggests that microbiota-induced metabolites affect host fatty acid peroxidation metabolism, which is correlated with the gene families of Acyl-CoA dehydrogenase long chain (ACADL), Acyl-CoA Oxidase (ACOX) and Acetyl-CoA Acyltransferase (ACAA). This integrated approach provides novel insights into heat stress problems and identifies potential biomarkers associated with heat stress.

PMID:38519440 | DOI:10.1080/10495398.2024.2331179

Am J Surg. 2024 Mar 18:S0002-9610(24)00175-2. doi: 10.1016/j.amjsurg.2024.03.014. Online ahead of print.

ABSTRACT

BACKGROUND: As the first comprehensive investigation into hospital readmissions following robotic hepatectomy for neoplastic disease, this study aims to fill a critical knowledge gap by evaluating risk factors associated with readmission and their impact on survival and the financial burden.

METHODS: The study analyzed a database of robotic hepatectomy patients, comparing readmitted and non-readmitted individuals post-operatively using 1:1 propensity score matching. Statistical methods included Chi-square, Mann-Whitney U, T-test, binomial logistic regression, and Kaplan-Meier analysis.

RESULTS: Among 244 patients, 44 were readmitted within 90 days. Risk factors included hypertension (p ​= ​0.01), increased Child-Pugh score (p ​< ​0.01), and R1 margin status (p ​= ​0.05). Neoadjuvant chemotherapy correlated with lower readmission risk (p ​= ​0.045). Readmissions didn’t significantly impact five-year survival (p ​= ​0.42) but increased fixed indirect hospital costs (p ​< ​0.01).

CONCLUSIONS: Readmission post-robotic hepatectomy correlates with hypertension, higher Child-Pugh scores, and R1 margins. The use of neoadjuvant chemotherapy was associated with a lower admission rate due to less diffuse liver disease in these patients. While not affecting survival, readmissions elevate healthcare costs.

PMID:38519401 | DOI:10.1016/j.amjsurg.2024.03.014

Sci Bull (Beijing). 2024 Mar 6:S2095-9273(24)00150-6. doi: 10.1016/j.scib.2024.03.006. Online ahead of print.

ABSTRACT

Recent advances in open neuroimaging data are enhancing our comprehension of neuropsychiatric disorders. By pooling images from various cohorts, statistical power has increased, enabling the detection of subtle abnormalities and robust associations, and fostering new research methods. Global collaborations in imaging have furthered our knowledge of the neurobiological foundations of brain disorders and aided in imaging-based prediction for more targeted treatment. Large-scale magnetic resonance imaging initiatives are driving innovation in analytics and supporting generalizable psychiatric studies. We also emphasize the significant role of big data in understanding neural mechanisms and in the early identification and precise treatment of neuropsychiatric disorders. However, challenges such as data harmonization across different sites, privacy protection, and effective data sharing must be addressed. With proper governance and open science practices, we conclude with a projection of how large-scale imaging resources and collaborations could revolutionize diagnosis, treatment selection, and outcome prediction, contributing to optimal brain health.

PMID:38519398 | DOI:10.1016/j.scib.2024.03.006

J Pediatr Surg. 2024 Mar 1:S0022-3468(24)00097-6. doi: 10.1016/j.jpedsurg.2024.02.015. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: As survival rates in childhood cancer progress significantly, health outcomes in adulthood are pivotal to quality of life (QoL). Female patients undergoing chemotherapy and radiation for childhood cancer may experience adverse effects such as gonadotoxicity-related ovarian insufficiency. Ovarian tissue cryopreservation (OTC) is well studied in adults, but has only recently started to be explored in an effort to preserve fertility in young patients with childhood cancer. This systematic review aims to critically highlight contemporary outcomes of cryopreservation in female pediatric cancer patients.

METHODS: A systematic search was conducted in PubMed, Embase, and Web of Science databases to identify English-language full text articles and abstracts published between 2004 and 2022 describing cryopreservation among female children (0-21 years old) with cancer. Abstracts and full-text articles were screened for inclusion. Subsequently, data from eligible studies was extracted and analyzed. Descriptive statistics were utilized to estimate overall outcomes of cryopreservation.

RESULTS: Of 104 abstracts and 34 full-text articles, 12 studies were included. Data was collected from 7 world countries and involved some 612 pediatric and adolescent patients with malignant disease. Most common cancers included hematological malignant disease (81%), CNS nervous system malignant tumors (56%), and sarcomas (39%). Of the 6 studies with full reporting, OTC was undertaken in 501 patients, and 5.9% (30/501) of these patients underwent ovarian tissue transplantation (OTT). After OTT, 27 patients desired pregnancy and 33% (9/27) became pregnant. Six of these 9 patients (67%) had live births.

CONCLUSIONS: Preliminary analysis showed that OTC has been successfully performed but not yet studied thoroughly in pediatric cancer patients in a longitudinal manner. This study has further shown that cryopreservation outcomes are mainly reported among adult patients living in high income countries, demonstrating a crucial need for long-term outcome studies focused on pediatric and prepuberal OTC, subsequent OTT, and potential pregnancy. This work is considered critical to aid standardize recommendations of fertility preservation in childhood cancer patients and to better inform the efficacy of these procedures to benefit patients in world nations of all fiscal income levels.

LEVEL OF EVIDENCE: Level III.

PMID:38519388 | DOI:10.1016/j.jpedsurg.2024.02.015

J Pediatr Surg. 2024 Feb 29:S0022-3468(24)00075-7. doi: 10.1016/j.jpedsurg.2024.01.043. Online ahead of print.

ABSTRACT

PURPOSE: Given the paucity of data on pediatric spontaneous pneumomediastinum (SPM), management is largely informed by extrapolation from adult studies or personal clinical experience, resulting in significant heterogeneity. The purpose of this study was to describe how pediatric patients with SPM are clinically managed at our institution and propose a treatment algorithm.

METHODS: Retrospective chart review of pediatric patients with SPM from April 2002 to December 2021 at a single Canadian tertiary care center. Data on medical history, presentation characteristics, clinical management, and complications were gathered. Descriptive and inferential statistics were used to analyze data.

RESULTS: We identified 63 patients for inclusion, median age was 15 years. Twenty-nine patients were transferred from another facility. Most common presenting symptoms were chest pain (72.3%), shortness of breath (44.6%), and subcutaneous emphysema (21.5%). Initial workup included chest x-ray (93.6%), CT scan (20.6%), and upper GI series (7.9%). There was no difference in the number of initial tests between admitted and discharged patients (p = 0.10). Of admitted patients (n = 35), 31.4% had primary SPM (no underlying comorbidity/inciting event) and 68.8% were secondary SPM (underlying comorbidity/inciting event). No patients with primary SPM developed complications or recurrences. In contrast, 16.7% of those with secondary SPM developed complications and 54.2% had at least one additional intervention after admission.

DISCUSSION: There is significant variability in diagnostic investigation and treatment of pediatric SPM at our center. Amongst primary SPM, additional tests did not change complication rate or recurrence, including those transferred from another facility. An expeditious treatment algorithm is warranted.

TYPE OF STUDY: Retrospective Cohort Study.

LEVEL OF EVIDENCE: III.

PMID:38519387 | DOI:10.1016/j.jpedsurg.2024.01.043

Ultrasound Med Biol. 2024 Mar 21:S0301-5629(24)00113-3. doi: 10.1016/j.ultrasmedbio.2024.02.015. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the diagnostic accuracy of ultrasound secondary signs of fractures in pediatric patients aged 5-15 y presenting to the emergency department with a clinically non-deformed distal forearm injury.

METHODS: This diagnostic study was conducted in South East Queensland, Australia. Emergency clinicians performed point-of-care ultrasound on eligible patients and recorded secondary signs of fractures (pronator quadratus hematoma [PQH] sign, periosteal hematoma, visible angulation) or physeal fractures (fracture-to-physis distance [FPD], physis alteration). The reference standard was the final fracture diagnosis determined by expert panel. The primary outcome was the diagnostic accuracy of secondary signs for cortical breach and physeal fractures. Diagnostic statistics were reported for each relevant secondary sign.

RESULTS: A total of 135 participants were enrolled. The expert panel diagnosed 48 “no” fracture, 52 “buckle” fracture and 35 “other” fracture. All “other” fractures were cortical breach fractures and included 15 Salter-Harris II fractures. The PQH sign demonstrated high sensitivity and moderate specificity to diagnose cortical breach fractures (91%, 95% Confidence Interval [CI] 78%-97% and 82%, 73%-88%). Poor sensitivity but high specificity was observed for the visible angulation and periosteal hematoma secondary signs. FPD <1cm showed perfect sensitivity and moderate specificity (100%, 80%-100% and 85%, 78%-90%) for diagnosis of Salter-Harris II fracture. Conversely, physis alteration showed poor sensitivity but excellent specificity (40%, 20%-64% and 99%, 95%-100%) for the diagnosis of Salter-Harris II fractures.

CONCLUSION: Ultrasound secondary signs showed good diagnostic accuracy for both cortical breach fractures and Salter-Harris II fractures. Future research should consider optimal use of secondary signs to improve diagnostic accuracy.

PMID:38519361 | DOI:10.1016/j.ultrasmedbio.2024.02.015

Vaccine. 2024 Mar 21:S0264-410X(24)00331-1. doi: 10.1016/j.vaccine.2024.03.044. Online ahead of print.

ABSTRACT

BACKGROUND: Despite some progress in pneumococcal immunization, the global burden of pneumococcal infection remains high, and pneumococcal disease remains a public health concern. Studies in China and abroad have found that 23-valent pneumococcal polysaccharide vaccine (PPV23) vaccination can effectively prevent invasive pneumococcal disease. This phase Ⅰ clinical study assessed the safety and immunogenicity of a PPV23 vaccine candidate.

METHODS: All subjects were randomly assigned to receive one dose intramuscular injection of experimental vaccine or control vaccine at a ratio of 1:1. The incidence of any adverse events was observed within 30 min, 0-7 days and 8-28 days post vaccination and the incidence of abnormal blood biochemical and blood routine indicators were tested on the 4th day post vaccination, the incidence of serious adverse events (SAEs) at 6 months post vaccination was recorded. Blood samples were collected prior to vaccination and on the 28th day post vaccination, and serum antibodies were detected by enzyme linked immunosorbent assay (ELISA).

RESULTS: The most common adverse reaction was pain at the injection site, followed by erythema. There was no significant difference of the incidence of systemic adverse reactions between the two vaccine groups. The adverse reactions observed in the trial were all common vaccination-related reactions, and no serious adverse reactions were observed. Compared to pre-vaccination, the (geometric mean concentrations) GMCs of IgG (immunoglobulin G) specific antibody against each serotype were all increased in the experimental group and the control group, there were statistical differences in seroconversion rates of serotypes 4 and 20 between the two vaccine groups.

CONCLUSION: This clinical study showed good safety of the PPV23 vaccine candidate produced by Ab&b Biotechnology Co., Ltd.JS had good safety after vaccination in people aged 2 years and older. At the same time, good immunogenicity was also demonstrated.

PMID:38519344 | DOI:10.1016/j.vaccine.2024.03.044