Category: Nevin Manimala

J Pediatr Endocrinol Metab. 2021 Dec 23. doi: 10.1515/jpem-2021-0587. Online ahead of print.

ABSTRACT

OBJECTIVES: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited connective tissue disorders, characterised by skeletal fragility. Patients with OI may also exhibit extra-skeletal features like blue or grey scleral colour, fragile skin, easy bruising, joint laxity, short stature, deafness, cardiac valve abnormalities and abnormal pulmonary function. The objective of this study is to describe genetic mutations, prevalence of hearing issues, cardiac complications and impaired pulmonary function in children with OI.

METHODS: This is a cross-sectional study of 23 Saudi children aged 6 months to 18 years who were diagnosed with OI. The revised Sillence classification (2,105) was used to classify the OI type. Whole exome sequencing was performed for genetic mutations. The hearing was assessed by either pure-tone audiometry and/or otoacoustic emission testing. Cardiac defects were screened by echocardiograms. Spirometry was performed to assess pulmonary function. Data were analysed with descriptive statistics.

RESULTS: Based on the Sillence classification, 16 patients had OI type III, 6 had type IV and 1 had type I. Of the18 patients who had genetic sequencing, 66.6% had autosomal dominant and 33.3% had autosomal recessive mutations. Among children who had screening, hearing loss was diagnosed in 53% (9/17), congenital cardiac malformations in 26% (5/19) and restrictive lung disease in 70% (7/10).

CONCLUSIONS: We found significant extra-skeletal features and a high yield of genetic mutations associated with OI. We suggest further studies to develop a screening protocol for extra-skeletal features in children with OI.

PMID:34954934 | DOI:10.1515/jpem-2021-0587

Isr Med Assoc J. 2021 Dec;23(12):794-800.

ABSTRACT

BACKGROUND: New direct acting antiviral agent (DAA) therapies are associated with a high sustained virological response rate (SVR) in hepatitis C virus (HCV) patients. The understanding of the impact of SVR on fibrosis stage is limited.

OBJECTIVES: To determine the effect of treatment with the DAAs on long-term liver fibrosis stages, as determined by shear-wave elastography (SWE) or FibroTest.

METHODS: Fibrosis stage was determined at baseline and at 6-month intervals after end of treatment (EOT), using two-dimensional SWE or FibroTest©; APRI and FIB-4 scores.

RESULTS: The study comprised 133 SVR12 patients. After a median follow-up of 15 months (range 6-33), liver fibrosis stage decreased by at least 1 stage in 75/133 patients (56%). Cirrhosis reversal was observed in 24/82 (29%). Repeated median liver stiffness SWE values in cirrhotic patients were 15.1 kPa at baseline (range 10.5-100), 13.4 kPa (range 5.5-51) at 6 months, and 11.4 kPa (range 6.1-35.8) at 12 months after EOT, P = 0.01. During the second year after EOT, no statistically significant differences in liver fibrosis stage in 12, 18, and 24 months were found. Splenomegaly was the only significant negative predictor of liver fibrosis regression during all time points of repetitive noninvasive assessment.

CONCLUSIONS: Following successful DAA treatment, the majority of our HCV patients with advanced fibrosis demonstrated significant improvement, as assessed by non-invasive methods. Advanced fibrosis stage was a negative predictor of fibrosis regression. Longer follow-up periods are required to further establish the impact of DAAs treatment in HCV patients with advanced fibrosis.

PMID:34954919

Isr Med Assoc J. 2021 Dec;23(12):805-810.

ABSTRACT

BACKGROUND: For locally advanced rectal cancer patients a watch-and-wait strategy is an acceptable treatment option in cases of complete tumor response. Clinicians need robust methods of patient selection after neoadjuvant chemoradiation.

OBJECTIVES: To predict pathologic complete response (pCR) using computer vision. To analyze radiomic wavelet transform to predict pCR.

METHODS: Neoadjuvant chemoradiation for patients with locally advanced rectal adenocarcinoma who passed computed tomography (CT)-based simulation procedures were examined. Gross tumor volume was examind on the set of CT simulation images. The volume has been analyzed using radiomics software package with wavelets feature extraction module. Statistical analysis using descriptive statistics and logistic regression was performed was used. For prediction evaluation a multilayer perceptron algorithm and Random Forest model were used.

RESULTS: In the study 140 patients with II-III stage cancer were included. After a long course of chemoradiation and further surgery the pathology examination showed pCR in 38 (27.1%) of the patients. CT-simulation images of tumor volume were extracted with 850 parameters (119,000 total features). Logistic regression showed high value of wavelet contribution to model. A multilayer perceptron model showed high predictive importance of wavelet. We applied random forest analysis for classifying the texture and predominant features of wavelet parameters. Importance was assigned to wavelets.

CONCLUSIONS: We evaluated the feasibility of using non-diagnostic CT images as a data source for texture analysis combined with wavelets feature analysis for predicting pCR in locally advanced rectal cancer patients. The model performance showed the importance of including wavelets features in radiomics analysis.

PMID:34954921

Isr Med Assoc J. 2021 Dec;23(12):788-793.

ABSTRACT

BACKGROUND: Up to 60% of inflammatory bowel disease (IBD) patients treated with infliximab develop antibodies to infliximab (ATI), which are associated with low drug levels and loss of response (LOR). Hence, mapping out predictors of immunogenicity toward infliximab is essential for tailoring patient-specific therapy. Jewish Sephardi ethnicity, in addition to monotherapy, has been previously identified as a potential risk factor for ATI formation and infliximab failure.

OBJECTIVES: To explore the association between Jewish sub-group ethnicity among patients with IBD and the risk of infliximab immunogenicity and therapy failure. To confirm findings of a previous cohort that addressed the same question.

METHODS: This retrospective cohort study included all infliximab-treated patients of Jewish ethnicity with regular prospective measurements of infliximab trough levels and ATI. Drug and ATI levels were prospectively measured, clinical data was retrieved from medical charts.

RESULTS: The study comprised 109 Jewish patients (54 Ashkenazi, 55 Sephardi) treated with infliximab. There was no statistically significant difference in proportion of ATI between Sephardi and Ashkenazi patients with IBD (32% Ashkenazi and 33% Sephardi patients developed ATI, odds ratio [OR] 0.944, P = 0.9). Of all variables explored, monotherapy and older age were the only factors associated with ATI formation (OR 0.336, 95% confidence interval 0.145-0.778, P = 0.01, median 34 vs. 28, interquartile range 28-48, 23-35 years, P = 0.02, respectively).

CONCLUSIONS: Contrary to previous findings, Sephardi Jewish ethnicity was not identified as a risk factor for ATI formation compared with Ashkenazi Jewish ethnicity. Other risk factors remained unchanged.

PMID:34954918

J Integr Bioinform. 2021 Dec 21. doi: 10.1515/jib-2020-0036. Online ahead of print.

ABSTRACT

The development of high-throughput genomic sequencing coupled with chromatin immunoprecipitation technologies allows studying the binding sites of the protein transcription factors (TF) in the genome scale. The growth of data volume on the experimentally determined binding sites raises qualitatively new problems for the analysis of gene expression regulation, prediction of transcription factors target genes, and regulatory gene networks reconstruction. Genome regulation remains an insufficiently studied though plants have complex molecular regulatory mechanisms of gene expression and response to environmental stresses. It is important to develop new software tools for the analysis of the TF binding sites location and their clustering in the plant genomes, visualization, and the following statistical estimates. This study presents application of the analysis of multiple TF binding profiles in three evolutionarily distant model plant organisms. The construction and analysis of non-random ChIP-seq binding clusters of the different TFs in mammalian embryonic stem cells were discussed earlier using similar bioinformatics approaches. Such clusters of TF binding sites may indicate the gene regulatory regions, enhancers and gene transcription regulatory hubs. It can be used for analysis of the gene promoters as well as a background for transcription networks reconstruction. We discuss the statistical estimates of the TF binding sites clusters in the model plant genomes. The distributions of the number of different TFs per binding cluster follow same power law distribution for all the genomes studied. The binding clusters in Arabidopsis thaliana genome were discussed here in detail.

PMID:34953471 | DOI:10.1515/jib-2020-0036

J Mech Behav Biomed Mater. 2021 Dec 18;126:105056. doi: 10.1016/j.jmbbm.2021.105056. Online ahead of print.

ABSTRACT

BACKGROUND: The objective of this study was to characterize and compare the mechanical properties of porcine pericranium and spinal dura mater, to evaluate the mechanical suitability of pericranium as a dural graft.

METHOD: Eighty-eight spinal dura (cervical, thoracic, and lumbar regions, in ventral longitudinal, dorsal longitudinal and circumferential orientations) and eighteen pericranium samples (ventral-dorsal, and lateral orientations) from four pigs, were harvested and subjected to uniaxial loading while hydrated. The stiffness, strain at toe-linear regions transition, strain at linear-yield regions transition and other structural and mechanical properties were measured. Stress-strain curves were fitted to a one-term Ogden model and Ogden parameters were calculated. Linear regression models with cluster-robust standard errors were used to assess the effect of region and orientation on material and structural properties.

RESULTS: Both spinal dura and pericranium exhibited distinct anisotropy and were stiffer in the longitudinal direction. The tissues exhibited structural and mechanical similarities especially in terms of stiffness and strains in the linear region. Stiffness ranged from 1.28 to 5.32 N/mm for spinal dura and 2.42-3.90 N/mm for pericranium. In the circumferential and longitudinal directions, the stiffness of spinal dura specimens was statistically similar to that of pericranium in the same orientation. The strain at the upper bound of the linear region of longitudinal pericranium (28.0%) was statistically similar to that of any spinal dura specimens (24.4-32.9%).

CONCLUSIONS: Autologous pericranium has advantageous physical properties for spinal duraplasty. The present study demonstrated that longitudinally oriented pericranium is mechanically compatible with spinal duraplasty procedures. Autologous pericranium grafts will likely support the mechanical loads transmitted from the spinal dura, but further biomechanical analyses are required to study the effect of the lower yield strain of circumferential pericranium compared to spinal dura. Finally, the Ogden parameters calculated for pericranium, and the spinal dura at each spinal level, will be useful for computational models incorporating these soft tissues.

PMID:34953436 | DOI:10.1016/j.jmbbm.2021.105056

Int Emerg Nurs. 2021 Dec 22;60:101125. doi: 10.1016/j.ienj.2021.101125. Online ahead of print.

ABSTRACT

BACKGROUND: Unplanned return visits to the emergency department (ED) have been associated with adverse outcomes and may reflect the quality of care delivered. Several studies speculate the reasons for return and suggest clinician behaviour as potentially influencing a patient’s decision to return to the ED. There is little research about this issue from the clinician’s perspective, which is necessary to inform future practice improvement.

METHODS: A descriptive cross sectional design was employed to ascertain perspectives on identification and management of return visits occurring within 48 hours of discharge. An electronic survey was distributed to all medical, nursing, and clerical staff at one ED. Descriptive statistics were used for quantitative data and content analysis was performed on textual data. Results were categorised as barriers or facilitators, then mapped to the Theoretical Domains Framework.

RESULTS: A response rate of 59.7% (n=86/144) was achieved. Staff reported increased levels of concern for this patient group but not all staff were aware of the policy for managing return patients (40.7%). Five barriers and three facilitators were identified that mapped to eight influencers of behaviour including knowledge, memory and environmental factors.

CONCLUSION: Overall, staff were aware of return patients but lacked familiarity with policy and processes to identify and commence relevant protocols. Further review of current practice as well as the patient perspective is required before any intervention to improve practice is developed.

PMID:34953437 | DOI:10.1016/j.ienj.2021.101125

Int J Surg Case Rep. 2021 Dec 20;90:106699. doi: 10.1016/j.ijscr.2021.106699. Online ahead of print.

ABSTRACT

INTRODUCTION: We describe the demographic, preoperative, surgical, anesthetic, and postoperative characteristics of patients who required a rapid response team (RRT) activation after major hip surgery. We determined the characteristics and outcomes of patients that require RRTs after major hip surgery, and their associations with mortality.

PRESENTATION OF CASES: We retrospectively reviewed adult patients undergoing major hip surgery in a university teaching hospital. We included patients who had an RRT or “code blue” activation post-surgery and within the index hospital admission. We extracted patient, surgical, anesthetic, and postoperative variables. We explored differences between patients who survived their index hospital stay and those who died.

DISCUSSION: 187 (9%) patients had a postoperative RRT activation. The median age was 84.0 (78-90) years; 125 (67%) were female, and most patients had significant comorbidities. The median Charlson Comorbidity Index (CCI) was 5.0 (4.0-7.0). Patients were frail (68%), ASA physical status ≥Class 3 (91%) and underwent emergency surgery (88%). Death after RRT activation occurred in 1 in 7 patients. Compared to patients who survived RRT activation, those who died had a higher mean CCI (6.5 [1.8] vs. 5.5 [2.1], P = 0.02), were more frail (80.1% vs. 56.5%, OR = 3.2, 95% CI: 1.2,8.1; P = 0.03), and received less intraoperative opioids (intravenous morphine equi-analgesia: median = 5.8 (0.1-8.20 vs. 11.7 (3.7-19.0) mg, P = 0.03).

CONCLUSION: Mortality after RRT activation is associated with non-modifiable patients factors rather than surgical or anesthesia factors. Our findings provide opportunities for the implementation of strategies aimed at improving postoperative outcomes.

PMID:34953425 | DOI:10.1016/j.ijscr.2021.106699

J Mech Behav Biomed Mater. 2021 Dec 11;126:105041. doi: 10.1016/j.jmbbm.2021.105041. Online ahead of print.

ABSTRACT

PURPOSE: The deformation of lamina cribrosa (LC) under the elevated intraocular pressure (IOP) might squeeze the retinal ganglion cell (RGC) axons and impair the visual function. Mechanical behaviors of LC and RGC axons are supposed to be related to the optic nerve damage of glaucoma patients. However, they cannot be independently studied with the existing methods because the LC and RGC axons intertwine in the LC area. This study proposed a feasible method to evaluate the respective mechanical properties of glial LC and RGC axons of rats.

METHODS: The atomic force microscope (AFM) nano-indentation experiment was performed on unfixed cryosection samples acquired from the glial LC tissues of eight eyes from four rats. For each sample, three regions of interests (ROIs) with sizes of 20 × 20 μm² were selected from the ventral, central and dorsal regions of the sample, respectively, and the nano-indentation was performed on 128 × 128 points within each ROI to obtain a Young’s modulus image. The glial LC and RGC axons were segmented on each modulus images using Otsu thresholding segmentation method, and their respective Young’s modulus was further extracted for statistical analysis.

RESULTS: Young’s modulus of glial LC and RGC axons are 297 ± 98 kPa and 76 ± 36 kPa in ventral regions, 342 ± 84 kPa and 84 ± 32 kPa in central regions, 280 ± 104 kPa and 75 ± 30 kPa in dorsal regions, respectively. No significant differences are found among the Young’s modulus of different regions, both for glial LC and RGC axons.

CONCLUSIONS: This study takes the nature property of the LC area as a composite material into consideration, and proposes a feasible method to distinguish between the glial LC and RGC axons and measure their respective Young’s modulus. These findings may provide useful information for establishing finite element models of the optic nerve head and promote the study on the deformation of the optic nerve under high intraocular pressure, and finally contribute to the early diagnosis of glaucoma.

PMID:34953434 | DOI:10.1016/j.jmbbm.2021.105041

J Trace Elem Med Biol. 2021 Dec 16;70:126914. doi: 10.1016/j.jtemb.2021.126914. Online ahead of print.

ABSTRACT

BACKGROUND: Today, although gadolinium based contrast agents have been frequently used in the field of medicine, there is limited data available whether gadolinium based agents affect the genome.

AIM: The present study aimed to investigate the genotoxic and cytotoxic potentials of gadoteric acid and gadoversetamide used as gadolinium-based contrast agents for magnetic resonance (MR) imaging.

MATERIAL AND METHODS: The cytokinesis-block micronucleus assay was applied to human peripheral blood lymphocytes to assess the genotoxicity measured as micronucleus (MN), nucleoplasmic bridge (NPBs) and nuclear bud (NBUDs) frequencies. Furthermore, cytokinesis-block proliferation index (CBPI) was calculated to determine cytostasis. Lymphocytes were treated with gadoteric acid at concentrations of 1.0, 2.5, 5.0, and 25 mM and with gadoversetamide at concentrations of 0.25, 1.0, 2.5, and 5.0 mM for 48 h.

RESULTS: Gadoteric acid did not cause significant increase in MN, NBPs and NBUDs frequencies and CBPI values at any concentration. Gadoversetamide induced significantly increase MN formation at concentration of 2.5 mM, NBP formation at concentrations of 1.0 and 2.5 mM, and NBUD formation at concentrations of 0.25, 1.0 and 2.5 mM. Additionally, gadoversetamide exposure resulted in statistically significant decrease in CBPI values compared to the control at concentrations of 2.5 and 5.0 mM. In addition, CBPI levels in response to concentrations of gadoversetamide was negatively and significantly associated with concentration.

CONCLUSION: These findings show that gadoteric acid does not have genotoxic or cytotoxic potential, while gadoversetamide might have both genotoxic and cytotoxic potential on human peripheral blood lymphocytes. As a comparison, gadoversetamide was found more genotoxic and cytotoxic.

PMID:34953388 | DOI:10.1016/j.jtemb.2021.126914