Category: Nevin Manimala

J Ultrasound Med. 2022 Jun 8. doi: 10.1002/jum.16032. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate ultrasound appearance and the survival outcomes for patients with primary thyroid lymphoma (PTL).

METHODS: Ultrasonic images and clinical characteristics from pathologically confirmed 69 PTL patients (2008-2019) were retrospectively analyzed. The clinical characteristics, ultrasonic characters, and prognostic factors were analyzed. Survival curves were plotted using the Kaplan-Meier method. Univariate and multivariate analyses were performed.

RESULTS: Of the 69 study patients, 23 were indolent PTL and 46 were aggressive PTL. Age (>70 years old) and elevated lactate dehydrogenase levels were statistically different clinical features between aggressive and indolent PTL. From ultrasonic images, 34 cases were nodular, 11 diffuse, and 24 mixed pattern. Mixed types displayed high invasiveness (45.7%) while diffuse types displayed higher inertness (39.1%), with statistically significant differences (P = .000). Invaded thyroid capsule and increased chaotic vascularity also showed significant differences between aggressive and indolent PTL. We also observed statistical difference in overall survival rates between aggressive and indolent PTL (P = .032). Single factor K-M analyses showed that age >70 years, aggressive pathology, and Ki67 >30% were positively correlated with the risk of poor PTL survival (P < .05).

CONCLUSIONS: Multimodal ultrasound provides accurate ultrasonographic information and facilitates PTL invasiveness diagnostics for improved clinical treatment. In addition, PTL patients aged >70 years, with aggressive pathology, and Ki67 >30% were more likely to have a poor survival outcome.

PMID:35673932 | DOI:10.1002/jum.16032

Clin Pediatr (Phila). 2022 Jun 8:99228221102827. doi: 10.1177/00099228221102827. Online ahead of print.

ABSTRACT

We aimed to investigate the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescription in children with community-acquired pneumonia (CAP). Antibiotic purchasing data were collected for children aged 3 months to 18 years diagnosed with CAP from November 2016 to April 2017 (pre-intervention period) and from November 2017 to April 2018 (post-intervention period). The intervention was a 1-day seminar for primary care pediatricians on the diagnosis and treatment of CAP in children according to national guidelines. There was a substantial decrease in the use of azithromycin after the intervention. In younger children, there was a 42% decrease, alongside an increased use of amoxicillin (P < .001). In older children, there was a smaller, non-statistically significant decrease in the use of azithromycin (P = .45). Our data demonstrate that the implementation of an ASP was associated with a reduction in the use of broad-spectrum antibiotics and macrolides and increased guideline adherence for the safe treatment of CAP.

PMID:35673872 | DOI:10.1177/00099228221102827

J Am Chem Soc. 2022 Jun 8. doi: 10.1021/jacs.2c04459. Online ahead of print.

ABSTRACT

Sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) is a membrane protein on the endoplasmic reticulum (ER) that transports Ca²⁺ from the cytosol into the ER. As its function is associated with various biological phenomena, SERCA has been recognized as a promising druggable target. Here, we report the second-strongest SERCA-inhibitory compound known to date, which we isolated from the marine cyanobacterium Leptochromothrix valpauliae and named iezoside (1). The structure of iezoside (1) is fundamentally different from that of any other SERCA inhibitor, and its potency is the strongest among marine natural products (K_i 7.1 nM). In this article, we report our comprehensive analysis of iezoside (1), which covers its isolation, structural characterization supported by density functional theory (DFT) calculations and statistical analysis, total synthesis, and clarification of the mode of action of its potent antiproliferative activity (IC₅₀ 6.7 ± 0.4 nM against HeLa cells).

PMID:35673891 | DOI:10.1021/jacs.2c04459

J R Soc Interface. 2022 Jun;19(191):20220094. doi: 10.1098/rsif.2022.0094. Epub 2022 Jun 8.

ABSTRACT

Gaussian processes (GPs), implemented through multivariate Gaussian distributions for a finite collection of data, are the most popular approach in small-area spatial statistical modelling. In this context, they are used to encode correlation structures over space and can generalize well in interpolation tasks. Despite their flexibility, off-the-shelf GPs present serious computational challenges which limit their scalability and practical usefulness in applied settings. Here, we propose a novel, deep generative modelling approach to tackle this challenge, termed PriorVAE: for a particular spatial setting, we approximate a class of GP priors through prior sampling and subsequent fitting of a variational autoencoder (VAE). Given a trained VAE, the resultant decoder allows spatial inference to become incredibly efficient due to the low dimensional, independently distributed latent Gaussian space representation of the VAE. Once trained, inference using the VAE decoder replaces the GP within a Bayesian sampling framework. This approach provides tractable and easy-to-implement means of approximately encoding spatial priors and facilitates efficient statistical inference. We demonstrate the utility of our VAE two-stage approach on Bayesian, small-area estimation tasks.

PMID:35673858 | DOI:10.1098/rsif.2022.0094

Open Biol. 2022 Jun;12(6):210337. doi: 10.1098/rsob.210337. Epub 2022 Jun 8.

ABSTRACT

The circulating low-density lipoprotein concentration in blood can be reduced by the administration of statins. Frequently simvastatin (SV) is prescribed. Due to the reported pleiotropic effects of SV the aim of this study was to evaluate mineralization effects on human adipose tissue-derived stromal cells upon administration of SV. After informed consent human adipose tissue-derived stromal cells were obtained from tissue surplus of regular treatments of 14 individuals. According to established protocols after adding various SV concentrations (0.01 µM, 0.1 µM, 1.0 µM, 2.0 µM), alkaline phosphate (osteoblastic marker), mineralization capability and viability were determined at day 18, 21 and 28. The Kruskal-Wallis test was performed for statistical analysis. After adding SV a dose-dependent significant decreased viability and levels of alkaline phosphatase (p < 0.01) and a significantly increased mineralization (p < 0.01) of the primary cultures was recognized during the late mineralization stage. Mineralization of the human adipose tissue-derived stromal cells was induced by SV, possibly originated from alternative pathways than the alkaline phosphatase pathway. Further investigations should be performed regarding switching into the osteoblastic differentiation and as a possible source of cells that can be used as the basis for a potential bone graft substitute, which may allow an extension of the field of application.

PMID:35673853 | DOI:10.1098/rsob.210337

Stat Med. 2022 Jun 8. doi: 10.1002/sim.9427. Online ahead of print.

ABSTRACT

Routinely-collected health data can be employed to emulate a target trial when randomized trial data are not available. Patients within provider-based clusters likely exert and share influence on each other’s treatment preferences and subsequent health outcomes and this is known as dissemination or spillover. Extending a framework to replicate an idealized two-stage randomized trial using routinely-collected health data, an evaluation of disseminated effects within provider-based clusters is possible. In this article, we propose a novel application of causal inference methods for dissemination to retrospective cohort studies in administrative claims data and evaluate the impact of the normality of the random effects distribution for the cluster-level propensity score on estimation of the causal parameters. An extensive simulation study was conducted to study the robustness of the methods under different distributions of the random effects. We applied these methods to evaluate baseline prescription for medications for opioid use disorder among a cohort of patients diagnosed with opioid use disorder and adjust for baseline confounders using information obtained from an administrative claims database. We discuss future research directions in this setting to better address unmeasured confounding in the presence of disseminated effects.

PMID:35673849 | DOI:10.1002/sim.9427

Rom J Morphol Embryol. 2021 Oct-Dec;62(4):1069-1075. doi: 10.47162/RJME.62.4.21.

ABSTRACT

The World Health Organization (WHO) estimates that one of five persons develops a cancer form during their lives. Out of the total of malignant cancer forms known up to the present, the statistics currently place breast cancer on the first rank at European level, as a type of neoplasm registered and treated with a standard protocol through the medical programs approved within public policies. The cost for the treatment of this type of oncological disease is enormous; for this reason, the state should manifest a direct interest for the prevention, early diagnose and investments in the research of mammary neoplasm. The coherence of national and European policies is achieved on a regular basis, subject to changes in Community legislation and the approval of European Commission (EC) documents that design unified approaches. This year, the emergence of the Europe’s Beating Cancer Plan, launched in 2021, has taken on the objective of investing in research and innovation, with a focus on the development of digital technologies that will increase expertise in genomics, onco-radiology, and digital health. The article analyzes the secondary data and empirical research collected at national and European level with the aim of highlighting the significant differences between public policies in Romania and France and identifying the pillars on which a national strategy similar to a functional European model can be built.

PMID:35673828 | DOI:10.47162/RJME.62.4.21

Rom J Morphol Embryol. 2021 Oct-Dec;62(4):991-1000. doi: 10.47162/RJME.62.4.11.

ABSTRACT

PURPOSE: Our retrospective study on 27 patients with a large mean macular hole diameter (MH-D) of 480.08±78.62 μm evaluates the usefulness of combining the current internal limiting membrane (ILM) inverted-flap surgical technique with silicone oil tamponade, which has been associated with the classical technique of ILM peeling.

RESULTS: Functional results: mean visual acuity (VA) improved to 0.89±0.11 logMar (logarithm of the minimum angle of resolution, at one month), 0.67±0.03 logMar (at three months), 0.52±0.04 logMar (at six months), 0.42±0.15 logMar (at one year) postoperative (final VA), with statistical linkage between preoperative VA and final VA (two-sample t-test, p=0.007), mean MH-D and final VA (regression analysis, p=0.003). We compared the results by MH size (Group A ≤400 μm – eight eyes and Group B >400 μm – 19 eyes), finding statistical variance (Bonett & Levene methods). Group A presented a final VA of 0.21±0.12 logMar, while Group B had 0.51±0.17 logMar. Successful closure was noted in 25 (92.59%) cases, with Group A having complete closure and external limiting membrane (ELM) restoration with ellipsoid zone (EZ) regeneration in six cases. Group B had successful closure in 17 (89.47%) cases with ELM restoration in 16 cases and EZ regeneration in seven (38.88%) cases, with reintervention in two cases. Restoration of the ELM was correlated [Pearson’s correlation coefficient (PCC) of 0.999, p=0.022] with successful closure, with overall restoration obtained in 24 (88.88%) cases and EZ regeneration in 13 (48.14%) cases.

CONCLUSIONS: ILM inverted-flap technique with silicone oil tamponade had favorable functional and anatomical outcomes. ELM restoration was associated with successful MH closure.

PMID:35673818 | DOI:10.47162/RJME.62.4.11

Rom J Morphol Embryol. 2021 Oct-Dec;62(4):1045-1050. doi: 10.47162/RJME.62.4.17.

ABSTRACT

Agenesis of permanent maxillary and mandibular canines is very rare; one to all four can be missing, isolated or in association with other missing teeth or with dental morphology abnormalities. Such cases can present functional, esthetic, and psychological problems, since the canine’s role in functional occlusion and in obtaining an aesthetic smile is crucial. Frequently, the canine’s absence from the arch is caused by impaction; its congenital absence is extremely rare in patients with no associated syndrome. The aim of this paper was to present a very rare case of a non-syndromic Romanian adult female patient with a unilateral permanent maxillary missing canine, in association with peg-shaped maxillary lateral permanent incisors, which can have a genetic cause, since the same morphological abnormality was present in her father and her younger sister, who also presented a rare situation of bilateral upper transposition between the canines and lateral incisors. The association of a permanent maxillary canine hypodontia with bilateral “peg laterals” and transposition between the maxillary canine and the peg-shaped lateral incisors is also rare as a family character in healthy patients. Future statistical studies are necessary to establish the incidence of permanent maxillary canine agenesis in Romanian population. Also, the article includes a detailed literature review of reported cases of agenesis of permanent maxillary canines.

PMID:35673824 | DOI:10.47162/RJME.62.4.17

Rom J Morphol Embryol. 2021 Oct-Dec;62(4):971-979. doi: 10.47162/RJME.62.4.09.

ABSTRACT

BACKGROUND AND AIM: Colonic serrated lesions are premalignant lesions, using an alternative malignization pathway, including multiple genetic and epigenetic alterations, as: mismatch repair deficiency due to MutL homolog 1 (MLH1) promoter methylation, tumor protein p53 (TP53) mutations, activating mutations of v-Raf murine sarcoma viral oncogene homolog B (BRAF) and Kirsten rat sarcoma viral oncogene homolog (KRAS). Our study aims to evaluate MLH1, BRAF and p53 immunohistochemical (IHC) status in sessile serrated lesions (SSLs), with and without dysplasia.

MATERIALS AND METHODS: This is a retrospective case-control study including 20 SSLs with dysplasia and 20 SSLs without dysplasia (matching sex and age). IHC expression of MLH1, BRAF and p53 was evaluated as the percent of nuclear loss of MLH1, cytoplasmic positivity of BRAF and nuclear positivity of p53. Data concerning age, sex, localization of the lesion, dysplasia and IHC results were statistically processed using Microsoft Excel.

RESULTS: We had very polymorphous patterns of IHC expression for BRAF, MLH1 and p53, especially in the dysplastic group. Thus, two patients were BRAF+∕MLH1-∕p53+, three were BRAF+∕MLH1-∕p53-, one was BRAF+∕MLH1+∕p53- and six were BRAF+∕MLH1+∕p53+. Dysplastic lesions without BRAF mutation exhibited the following phenotype: one case BRAF-∕MLH1-∕p53+, four BRAF-∕MLH1-∕p53- and three BRAF-∕MLH1+∕p53+. In the control group (SSLs without dysplasia), there was a more homogenous distribution of cases: eight cases BRAF+∕MLH1+∕p53-, seven BRAF-∕MLH1+∕p53-, one BRAF-∕MLH1-∕p53+, two BRAF-∕MLH1-∕p53- and two BRAF-∕MLH1+∕p53+.

CONCLUSIONS: There are more routes on the serrated pathway, with different mutations and time of acquisition of each genetic or epigenetic lesion with the same morphological result. These lesions should be stratified according to their risk to poor outcome and their need to further surveillance.

PMID:35673816 | DOI:10.47162/RJME.62.4.09