bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors and a novel predictive model for intravascular immunoglobulin resistance in Kawasaki disease
Authors: Wang Junjie , Huang Xiaohui , Guo Donghao
Published: September 2023

Background

Early identification of intravenous immunoglobulin (IVIG) resistance contributes to better management of Kawasaki disease (KD). This study aims to establish an effective prediction model for IVIG resistance in the Chinese population.

Methods

A total of 658 eligible patients diagnosed with KD were enrolled in this study, with 461 in the training cohort and 197 in the validation cohort. The demographic characteristics and potential risk factors were compared between IVIG-responsive and resistant groups. Predictors were selected by the Akaike information criterion. The nomogram’s performance was evaluated by calibration curve, decision curve analysis, and operating characteristic curve.

Results

White blood cell counts (WBC), neutrophil-lymphocyte ratio (N/L ratio), hematocrit (HCT), albumin (ALB), total bilirubin (TBIL), lactate dehydrogenase (LDH), and creatinine (Cr) were detected as predictors of IVIG resistance. A predictive nomogram incorporating these predictors was constructed using the training cohort. The calibration curve and decision curve analysis showed good discrimination and calibration of the proposed nomogram in both training and validation sets, and the area under the receiver operating characteristic curve (AUROC) in both sets was 75.8% and 74.2%, respectively.

Conclusion

This study identified WBC, N/L ratio, HCT, ALB, TBIL, LDH, and Cr as predictors for IVIG resistance in patients with KD. The proposed novel nomogram with a high level of accuracy and reliability may benefit clinical decision-making upon treatment initiation.
Elucidating disease-associated mechanisms triggered by pollutants via the epigenetic landscape using large-scale ChIP-Seq data
Authors: Zou Zhaonan , Yoshimura Yuka , Yamanishi Yoshihiro , Oki Shinya
Published: September 2023

Background

Despite well-documented effects on human health, the action modes of environmental pollutants are incompletely understood. Although transcriptome-based approaches are widely used to predict associations between chemicals and disorders, the molecular cues regulating pollutant-derived gene expression changes remain unclear. Therefore, we developed a data-mining approach, termed “DAR-ChIPEA,” to identify transcription factors (TFs) playing pivotal roles in the action modes of pollutants.

Methods

Large-scale public ChIP-Seq data (human, n = 15,155; mouse, n = 13,156) were used to predict TFs that are enriched in the pollutant-induced differentially accessible genomic regions (DARs) obtained from epigenome analyses (ATAC-Seq). The resultant pollutant–TF matrices were then cross-referenced to a repository of TF–disorder associations to account for pollutant modes of action. We subsequently evaluated the performance of the proposed method using a chemical perturbation data set to compare the outputs of the DAR-ChIPEA and our previously developed differentially expressed gene (DEG)-ChIPEA methods using pollutant-induced DEGs as input. We then adopted the proposed method to predict disease-associated mechanisms triggered by pollutants.

Results

The proposed approach outperformed other methods using the area under the receiver operating characteristic curve score. The mean score of the proposed DAR-ChIPEA was significantly higher than that of our previously described DEG-ChIPEA (0.7287 vs. 0.7060; Q = 5.278 × 10–42; two-tailed Wilcoxon rank-sum test). The proposed approach further predicted TF-driven modes of action upon pollutant exposure, indicating that (1) TFs regulating Th1/2 cell homeostasis are integral in the pathophysiology of tributyltin-induced allergic disorders; (2) fine particulates (PM2.5) inhibit the binding of C/EBPs, Rela, and Spi1 to the genome, thereby perturbing normal blood cell differentiation and leading to immune dysfunction; and (3) lead induces fatty liver by disrupting the normal regulation of lipid metabolism by altering hepatic circadian rhythms.

Conclusions

Highlighting genome-wide chromatin change upon pollutant exposure to elucidate the epigenetic landscape of pollutant responses outperformed our previously described method that focuses on gene-adjacent domains only. Our approach has the potential to reveal pivotal TFs that mediate deleterious effects of pollutants, thereby facilitating the development of strategies to mitigate damage from environmental pollution.
MyD88 dimerization inhibitor ST2825 targets the aggressiveness of synovial fibroblasts in rheumatoid arthritis patients
Authors: Ramirez-Perez Sergio , Vekariya Rushi , Gautam Surabhi , Reyes-Perez Itzel Viridiana , Drissi Hicham , Bhattaram Pallavi
Published: September 2023

Background

Dimerization of the myeloid differentiation primary response 88 protein (MyD88) plays a pivotal role in the exacerbated response to innate immunity-dependent signaling in rheumatoid arthritis (RA). ST2825 is a highly specific inhibitor of MyD88 dimerization, previously shown to inhibit the pro-inflammatory gene expression in peripheral blood mononuclear cells from RA patients (RA PBMC). In this study, we elucidated the effect of disrupting MyD88 dimerization by ST2825 on the pathological properties of synovial fibroblasts from RA patients (RA SFs).

Methods

RA SFs were treated with varying concentrations of ST2825 in the presence or absence of bacterial lipopolysaccharides (LPS) to activate innate immunity-dependent TLR signaling. The DNA content of the RA SFs was quantified by imaging cytometry to investigate the effect of ST2825 on different phases of the cell cycle and apoptosis. RNA-seq was used to assess the global response of the RA SF toward ST2825. The invasiveness of RA SFs in Matrigel matrices was measured in organoid cultures. SFs from osteoarthritis (OA SFs) patients and healthy dermal fibroblasts were used as controls.

Results

ST2825 reduced the proliferation of SFs by arresting the cells in the G0/G1 phase of the cell cycle. In support of this finding, transcriptomic analysis by RNA-seq showed that ST2825 may have induced cell cycle arrest by primarily inhibiting the expression of critical cell cycle regulators Cyclin E2 and members of the E2F family transcription factors. Concurrently, ST2825 also downregulated the genes encoding for pain, inflammation, and joint catabolism mediators while upregulating the genes required for the translocation of nuclear proteins into the mitochondria and members of the mitochondrial respiratory complex 1. Finally, we demonstrated that ST2825 inhibited the invasiveness of RA SFs, by showing decreased migration of LPS-treated RA SFs in spheroid cultures.

Conclusions

The pathological properties of the RA SFs, in terms of their aberrant proliferation, increased invasiveness, upregulation of pain and inflammation mediators, and disruption of mitochondrial homeostasis, were attenuated by ST2825 treatment. Taken together with the previously reported anti-inflammatory effects of ST2825 in RA PBMC, this study strongly suggests that targeting MyD88 dimerization could mitigate both systemic and synovial pathologies in a variety of inflammatory arthritic diseases.
Plasma aryl hydrocarbon receptor associated with epicardial adipose tissue in men: a cross-sectional study
Authors: Cheng Yu-Cheng , Ma Wei-Chun , Li Yu-Hsuan , Wu Junyi , Liang Kae-Woei , Lee Wen-Jane , Liu Hsiu-Chen , Sheu Wayne Huey-Herng , Lee I-Te
Published: September 2023

Background

Epicardial adipose tissue (EAT) is a type of ectopic fat with endocrine and paracrine functions. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that responds to environmental stimuli. AhR expression is associated with obesity. In this cross-sectional study, we aimed to determine the relationship between circulating AhR concentrations and EAT.

Methods

A total of 30 men with obesity and 23 age-matched men as healthy controls were enrolled. Plasma AhR concentrations were determined at fasting. The EAT thickness was measured on the free wall of the right ventricle from the basal short-axis plane by magnetic resonance imaging.

Results

The participants with obesity had a higher plasma AhR level than the controls (81.0 ± 24.5 vs. 65.1 ± 16.4 pg/mL, P = 0.010). The plasma AhR level was positively correlated with EAT thickness (correlation coefficient = 0.380, P = 0.005). After adjusting for fasting glucose levels, plasma AhR levels were still significantly associated with EAT thickness (95% CI 0.458‒5.357, P = 0.021) but not with body mass index (P = 0.168).

Conclusion

Plasma AhR concentrations were positively correlated with EAT thickness on the free wall of the right ventricle in men. Further investigations are needed to evaluate the causal effects and underlying mechanisms between AhR and EAT.
Utility of contrast enhanced ultrasound (CEUS) in penile trauma
Authors: Gómez-Bermejo Miguel A. , Huang Dean Y. , Bertolotto Michele , Sidhu Paul S.
Published: September 2023

Penile traumatic injuries are rare with potentially severe consequences, with clinical assessment challenging due to pain and swelling. Ultrasound is the primary imaging modality for assessing the penis. It has a high spatial resolution and rapid availability and is portable. Contrast enhanced ultrasound is an advanced ultrasound technique that adds real-time dynamic vascular imaging safely, increasing diagnostic precision and confidence, allowing for better therapeutic management of traumatic penile injuries. Contrast enhanced ultrasound helps to delineate the extent of a haematoma, distinguishing this from the herniated corpus cavernosum, detecting the point of rupture of the tunica albuginea, showing vascular abnormalities, localising a dislocated penis and determining penile viability. The integrity of the urethra may be assessed with intracavitary contrast enhanced ultrasound. Additionally, contrast enhanced ultrasound allows monitoring of the response to endovascular and surgical treatment. This review aims to detail the anatomy and pathogenesis of penile trauma, to give guidance on optimising the contrast enhanced ultrasound technique and to obtain diagnostic examinations. Illustration of the spectrum of aspects of penile trauma will be complemented with a literature review.

Critical relevance statement Contrast enhanced ultrasound is a safe and efficient imaging modality that allows for highly accurate diagnoses, helping achieve more successful and conservative treatments of penile trauma complications.

Key points

• Ultrasound is an accurate and safe imaging test for penile trauma.

• CEUS adds dynamic vascular imaging in real-time increasing diagnostic confidence.

• CEUS can delineate penile haematomas, locate fractures and demonstrate vessel integrity.

• CEUS potentially allows for more conservative treatment of penile trauma complications.

Graphical Abstract
Early chest CT abnormalities to predict the subsequent occurrence of chronic lung allograft dysfunction
Authors: Habert Paul , Chetrit Elsa , Coiffard Benjamin , Bregeon Fabienne , Thomas Pascal , Loundou Anderson , Bermudez Julien , Reynaud-Gaubert Martine , Gaubert Jean-Yves
Published: September 2023

Introduction

Chronic lung allograft dysfunction (CLAD) can take two forms: bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). The aim was to determine if chest-CT abnormalities after lung transplantation (LTx) could predict CLAD before respiratory functional deterioration.

Materials and methods

This monocentric retrospective study analyzed consecutive patients who underwent LTx from January 2015 to December 2018. Initial CT post-LTx (CTi) and a follow-up CT at least 9 months post-LTx (CTf) were reviewed. CLAD was defined as a persistent respiratory functional decline (> 20% of basal FEV1) outside acute episode. A Cox regression was performed in univariate, then in multivariate analysis (including features with p < 0.01 in univariate or of clinical importance) to determine risk factors for CLAD. Subgroup analyses were made for BOS, RAS, and death.

Results

Among 118 LTx patients (median (min–max) 47 (18–68) years), 25 developed CLAD during follow-up (19 BOS). The median time to CLAD since LTx was 570 days [150–1770]. Moderate pulmonary artery stenosis (30–50%) was associated with the occurrence of CLAD on CTi (hazard ratio HR = 4.6, CI [1.6–13.2]) and consolidations and pleural effusion on CTf (HR = 2.6, CI [1.3–4.9] and HR = 4.5, CI [1.5–13.6] respectively). The presence of mosaic attenuation (HR = 4.1, CI [1.4–12.5]), consolidations (HR = 2.6, CI [1.3–5.4]), and pleural effusions (p = 0.01, HR = 5.7, CI [1.4–22.3]) were risk factors for BOS on CTf. The consolidations (p = 0.029) and pleural effusions (p = 0.001) were risk factors for death on CTf.

Conclusions

CTi and CTf in the monitoring of LTx patients could predict CLAD. Moderate pulmonary artery stenosis, mosaic pattern, parenchyma condensations, and pleural effusions were risk factors for CLAD.

Critical relevance statement

There is a potential predictive role of chest CT in the follow-up of LTx patients for chronic lung allograft dysfunction (CLAD). Early chest CT should focus on pulmonary artery stenosis (risk factor for CLAD in this study). During the follow-up (at least 9 months post-LTx), parenchymal consolidations and pleural effusions were shown to be risk factors for CLAD, and death in subgroup analyses.

Key points

• Pulmonary artery stenosis (30–50%) on initial chest-CT following lung transplantation predicts CLAD HR = 4.5; CI [1.6–13.2].

• Pleural effusion and consolidations 1 year after lung transplantation predict CLAD and death.

• Early evaluation of lung transplanted patients should evaluate pulmonary artery anastomosis.

Graphical Abstract
Predictive modeling based on tumor spectral CT parameters and clinical features for postoperative complications in patients undergoing colon resection for cancer
Authors: Tan Xiaoying , Yang Xiao , Hu Shudong , Chen Xingbiao , Sun Zongqiong
Published: September 2023

Background

Colon cancer is a particularly prevalent malignancy that produces postoperative complications (POCs). However, limited imaging modality exists on the accurate diagnosis of POCs. The purpose of this study was therefore to construct a model combining tumor spectral CT parameters and clinical features to predict POCs before surgery in colon cancer.

Methods

This retrospective study included 85 patients who had preoperative abdominal spectral CT scans and underwent radical colon cancer resection at our institution. The patients were divided into two groups based on the absence (no complication/grade I) or presence (grades II–V) of POCs according to the Clavien-Dindo grading system. The visceral fat areas (VFA) of patients were semi-automatically outlined and calculated on L3-level CT images using ImageJ software. Clinical features and tumor spectral CT parameters were statistically compared between the two groups. A combined model of spectral CT parameters and clinical features was established by stepwise regression to predict POCs in colon cancer. The diagnostic performance of the model was evaluated using the receiver operating characteristic (ROC) curve, including area under the curve (AUC), sensitivity, and specificity.

Results

Twenty-seven patients with POCs and 58 patients without POCs were included in this study. MonoE40keV-VP and VFA were independent predictors of POCs. The combined model based on predictors yielded an AUC of 0.84 (95% CI: 0.74–0.91), with a sensitivity of 77.8% and specificity of 87.9%.

Conclusions

The model combining MonoE40keV-VP and VFA can predict POCs before surgery in colon cancer and provide a basis for individualized management plans.

Critical relevance statement

The model combining MonoE40keV-VP and visceral fat area can predict postoperative complications before surgery in colon cancer and provide a basis for individualized management plans.

Key points

• Visceral fat area and MonoE40keV-VP were independent predictors of postoperative complications in colon cancer.

• The combined model yielded a high AUC, sensitivity, and specificity in predicting postoperative complications.

• The combined model was superior to the single visceral fat area or MonoE40keV-VP in predicting postoperative complications.

Graphical Abstract
Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report
Authors: del Giglio Auro , da Costa Aguiar Alves Beatriz , Murad André Márcio , Fonseca Fernando Luiz Affonso
Published: September 2023

Background

TheBRCA2gene is a well-known tumor suppressor gene implicated in breast and ovarian cancers.BRCA1/2mutations can be sensitive to poly ADP-ribose polymerase (PARP) inhibitors such as olaparib. However, some of these patients develop resistance to this treatment and an essential factor contributing to acquired insensitivity is the occurrence of reversion mutations in theBRCA1/2genes.

Case presentation

We report the case of a 65-year-old Brazilian female patient who had previously been diagnosed with metastatic lung carcinoma carrying aBRCA2mutation that had extended to the central nervous system. Following disease progression, olaparib was administered, resulting in a stabilizing effect on her condition for ~ 30 months. During a routine follow-up, a new triple-negative breast tumor was found. Genetic testing revealed the presence of two distinctBRCA2gene mutations in the breast tumor. The original mutation (p.Val220Ilefs4) led to a frameshift, culminating in the production of a truncated and non-functional BRCA2 protein; the second mutation, K437fs22, rectified the reading frame of exon 11. Consequently, Rad51 could properly bind to BRCA2—an essential protein crucial for DNA repair. This restoration resulted in a functional BRCA2 protein, effectively elucidating the clinical resistance observed in the new breast tumor in this case.

Conclusions

This case report highlights the clinical significance of comprehensive next-generation sequencing analyses for lung adenocarcinomas, both at diagnosis and upon progression. Such analyses enable informed decisions regarding targeted therapies and facilitate a deeper comprehension of resistance mechanisms.
Efficacy of fractional CO2 laser in combination with stromal vascular fraction (SVF) compared with fractional CO2 laser alone in the treatment of burn scars: a randomized controlled clinical trial
Authors: Roohaninasab Masoumeh , Khodadad Fariba , Sadeghzadeh-Bazargan Afsaneh , Atefi Najmolsadat , Zare Sona , Jafarzadeh Alireza , Rahimi Seyyedeh Tahereh , Nouri Maryam , Nilforoushzadeh Mohammad Ali , Behrangi Elham , Goodarzi Azadeh
Published: September 2023

Background

The appearance of skin scars is known as one of the main side effects of skin burns. Stromal vascular fraction (SVF), as a rich source of cell populations with tissue regeneration properties, plays an important role in the healing of skin lesions. Fractional CO2 lasers have occupied a special place in treating skin lesions, particularly skin scars, since their introduction. Our study aimed to compare the combination of SVF and fractional CO2 laser with fractional CO2 laser alone in the treatment of burn scars.

Method

This double-blind clinical trial study was conducted on ten patients with burn scars that were treated three times with a fractional CO2 laser at site of burn lesions, and one of the two areas studied was randomly injected with SVF. Two months after completion of the procedure, patients' scars were assessed using the Vancouver scar scale (VSS), biometric criteria, and physician and patient satisfaction ratings.

Results

The results confirmed a significant improvement in VSS, cutometry, R7 criteria, complete density sonography, and skin density sonography in the fractional CO2 laser-treated group. The VSS criteria, epidermal thickness sonography, complete density sonography, and skin density sonography in the group treated with the combination of fractional CO2 laser and SVF also showed significant improvement. The VSS criteria and melanin index of Mexameter in the group treated with SVF in combination with fractional CO2 laser were significantly better than the group treated with fractional CO2 laser alone. Also, physician and patient satisfaction in the group treated with SVF injection in combination with fractional CO2 laser was significantly higher than the other group.

Conclusion

The results confirm the efficacy of SVF injection in combination with fractional CO2 laser in the treatment of burn scars and can be considered as a treatment option for better management of these lesions.

Trial registration: The study protocol was retrospectively registered at Iranian Registry of Clinical Trials with code: IRCT20210515051307N1, Registration date: 2021-11-14, URL: https://www.irct.ir/trial/56337.
Nano-seq analysis reveals different functional tendency between exosomes and microvesicles derived from hUMSC
Authors: Yu Dong , Mei Yue , Wang Ling , Zhao Yunpeng , Fan Xingfei , Liang Dong , Li Li , Zhu Jie , Bi Sisi , Wang Xue , Qi Zhongquan , Zhu Lie , Wang Yue
Published: September 2023

Background

Extracellular vesicles (EVs) from human umbilical cord mesenchymal stem cells (hUMSCs) are widely considered to be the best mediators for cell-free therapy. An understanding of their composition, especially RNA, is particularly important for the safe and precise application of EVs. Up to date, the knowledge of their RNA components is limited to NGS sequencing and cannot provide a comprehensive transcriptomic landscape, especially the long and full-length transcripts. Our study first focused on the transcriptomic profile of hUMSC-EVs based on nanopore sequencing.

Methods

In this study, different EV subtypes (exosomes and microvesicles) derived from hUMSCs were isolated and identified by density gradient centrifugation. Subsequently, the realistic long transcriptomic profile in different subtypes of hUMSC-EVs was systematically compared by nanopore sequencing and bioinformatic analysis.

Results

Abundant transcript variants were identified in EVs by nanopore sequencing, 69.34% of which transcripts were fragmented. A series of full-length and long transcripts was also observed and showed a significantly higher proportion of intact or near-complete transcripts in exosomes than that in microvesicles derived from hUMSCs. Although the composition of RNA biotypes transported by different EV subtypes was similar, the distribution of transcripts and genes revealed the inter-heterogeneity and intra-stability between exosomes and microvesicles. Further, 85 different expressed transcripts (56 genes) and 7 fusion genes were identified. Pathway enrichment analysis showed that upregulated-expressed genes in microvesicles were mainly enriched in multiple neurodegenerative diseases, while upregulated-expressed genes in exosomes were mainly enriched in neutrophil extracellular trap formation, suggesting different functional tendencies of EV subtypes.

Conclusions

This study provides a novel understanding of different types of hUMSC-EVs, which not only suggests different transcriptome sorting mechanisms between exosomes and microvesicles, but also shows that different EV subtypes from the same source have different physiological functions, suggesting distinct clinical application prospects.
Multidisciplinary expert panel report on fluid stewardship: perspectives and practice
Authors: Malbrain Manu L. N. G. , Caironi Pietro , Hahn Robert G. , Llau Juan V. , McDougall Marcia , Patrão Luís , Ridley Emily , Timmins Alan
Published: September 2023

Although effective and appropriate fluid management is a critical aspect of quality care during hospitalization, the widespread adoption of consistent policies that ensure adequate fluid stewardship has been slow and heterogenous. Despite evidence-based guidelines on fluid management being available, clinical opinions continue to diverge on important aspects of care in this setting, and the consistency of guideline implementation is far from ideal. A multidisciplinary panel of leading practitioners and experts convened to discuss best practices for ongoing staff education, intravenous fluid therapy, new training technologies, and strategies to track the success of institutional fluid stewardship efforts. Fluid leads should be identified in every hospital to ensure consistency in fluid administration and monitoring. In this article, strategies to communicate the importance of effective fluid stewardship for the purposes of education, training, institutional support, and improvement of patient outcomes are reviewed and recommendations are summarized.

Graphical Abstract
Focal adhesion kinase: from biological functions to therapeutic strategies
Authors: Tan Ximin , Yan Yuheng , Song Bin , Zhu Shuangli , Mei Qi , Wu Kongming
Published: September 2023

Focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, is a vital participant in primary cellular functions, such as proliferation, survival, migration, and invasion. In addition, FAK regulates cancer stem cell activities and contributes to the formation of the tumor microenvironment (TME). Importantly, increased FAK expression and activity are strongly associated with unfavorable clinical outcomes and metastatic characteristics in numerous tumors. In vitro and in vivo studies have demonstrated that modulating FAK activity by application of FAK inhibitors alone or in combination treatment regimens could be effective for cancer therapy. Based on these findings, several agents targeting FAK have been exploited in diverse preclinical tumor models. This article briefly describes the structure and function of FAK, as well as research progress on FAK inhibitors in combination therapies. We also discuss the challenges and future directions regarding anti-FAK combination therapies.
A case of laparoscopic sigmoidectomy using thermography for colonic blood flow assessment
Authors: Kako Tomohiro , Kimura Masahiro , Nomura Ryo , Uehara Shuhei , Uematsu Hiroshi , Nakaya Seiichi , Maeda Yuzo , Tsuboi Ken , Harata Koshiro , Takiguchi Shuji
Published: September 2023

Background

Indocyanine green (ICG) fluorescence imaging is widely used in gastrointestinal surgery and is considered useful for reducing anastomotic leakage; however, because ICG remains in the tissue for a certain amount of time, we occasionally must re-evaluate colonic blood flow over a short time period during surgery. Herein, we verify the usefulness of thermography (TG) for evaluating colonic blood flow in a patient who underwent a laparoscopic sigmoidectomy for sigmoid colon cancer.

Case presentation

The patient is 43-year-old man who underwent laparoscopic resection of the sigmoid colon for colon cancer. After vascular treatment of the colonic mesentery, ICG/TG identified the boundary between ischemic and non-ischemic colon tissues. An additional 2 cm of colonic mesentery was resected because of the presence of a diverticulum noted at the intended site of oral anastomosis when attaching the anvil head. After additional vascular treatment of the colonic mesentery and administration of ICG, fluorescence was observed in the colon; however, TG identified the zone of the temperature transition on the surface of the colonic mesentery, even after additional colonic mesentery resection in the same region as previously observed. This zone was used as the cut-off line. There were no complications, such as anastomotic leakage, after the surgery.

Conclusion

Although accumulation of similar cases is necessary, TG has the potential for use as an auxiliary diagnostic tool in clinical practice. TG can depict the presence or absence of blood flow based on surface temperature without the use of imaging agents, and is inexpensive and easy to perform.
Vitamin D3 supplementation improves spatial memory, muscle function, pain score, and modulates different functional physiological biomarkers in vitamin D3 deficiency diet (VDD)-induced rats model
Authors: Trivedi Mahendra Kumar , Branton Alice , Trivedi Dahryn , Mondal Sambhu , Jana Snehasis
Published: September 2023

Background

Vitamin D Deficiency is recognized as a pandemic, which is associated with high mortality. An inadequate level of vitamin D is associated with autoimmune diseases, hypertension, and cancer. The study was aimed to assess the pharmacological effects of chronic vitamin D3 supplementation on the manipulation diet regiment of deprived cholecalciferol (vitamin D3 deficient diet, VDD) rats.

Methods

Memory performance (Y-maze task), muscular function (muscle grip strength), and pain score (pressure application measurement meter) were measured. Functional biomarkers were measured using ELISA method in different matrix viz. in serum (parathyroid hormone; PTH, calcitonin, thyroxine, and C-reactive protein; CRP, 25-OH Vit D3), and in CSF (klotho and β-endorphin). 25-OH Vit D3 was also estimated in liver and kidney homogenate using ELISA. Vitamin D receptor (VDR) was measured spectrophotometrically in liver and adipose tissue.

Results

VDD-induced rats showed a decrease in number of entries and time spent in the novel arm and spontaneous alternations in the Y-maze task. Significant improvements of neuromuscular function and pain score after addition of vitamin D3. In comparison to the VDD group, VDR expression (liver) and active metabolites of vitamin D3 (25-OH vit.D3) in serum were significantly higher by 48.23% and 280%, respectively. The PTH and CRP levels were significantly reduced by 32.5% and 35.27%, respectively, whereas calcitonin was increased by 36.67% compared with the VDD group. Klotho and β-endorphin expressions in cerebrospinal fluid were significantly elevated by 19.67% and 133.59%, respectively, compared to VDD group.

Conclusions

Overall, the results indicate that supplementation of cholecalciferol significantly improved spatial memory impairment, VDR expression, and may provide an opportunity to manage vitamin D deficiencies.
Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms
Authors: Wang Zirui , Wang Cong , Fei Xiaohua , Wu Haixing , Niu Peiqin , Shen Changxing
Published: September 2023

Introduction

Thymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy for COVID-19 associated pneumonia is not yet fully researched, another issue, whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to multi-angle evaluate the clinical efficacy of Thymalfasin therapy for COVID-19 pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital.

Methods

The primary index of observation was whether progression to severe pneumonia occurred within a week after admission, and the secondary indexes were the length of hospital stay, time of negative conversion of COVID-19 antigen, the number of peripheral lymphocytes and white blood cells (WBC), and C-reactive protein (CRP) and procalcitonin (PCT) levels,and the control of pneumonia related symptoms, for example, fever, listlessness, inflammatory exudate area shown on lung CT (%).

Results

The length of hospital stay of patients in Thymalfasin group was significantly shorter than that of patients in the control group (p < 0.01). The proportion of relief of pneumonia related symptoms (fever, fatigue) in the Thymalfasin therapy group was significantly higher than that in the control group, and the inflammatory exudate area shown on CT was significantly lower than that in the control group (p < 0.05). Multivariate logistic regression analysis showed that the use of Thymalfasin was an independent protective factor affecting the progression to severe pneumonia. Multifactorial Cox model analysis indicated that negative conversion of COVID-19 antigen was significantly faster in patients using Thymalfasin and younger patients.

Conclusion

Thymalfasin therapy has shown excellent clinical efficacy in the treatment of COVID-19 pneumonia, it can reduce inflammatory reactions, promote the relief of COVID-19 pneumonia related symptoms such as fever and fatigue, facilitate effusion absorption, and accelerate COVID-19 pneumonia recovery. Thymalfasin can prevent progression of common COVID-19 infection to severe pneumonia via multiple immunity-enhancing and anti-inflammatory protective mechanisms.
Prevalence of bronchial asthma and correlation between the chemokine receptor 3 gene polymorphism and clinical asthma phenotypes among Egyptian asthmatic children
Authors: Zedan Magdy Mohamed , Wassefy Mona El , Khashaba Eman Omar , Sallam Hagar , Mabood Suzy Abd El
Published: September 2023

Background

Asthma is a chronic inflammatory airway disease characterized by episodic reversible airway obstruction that variably presents with cough, wheezing, shortness of breath, or chest tightness. It is a multigenetic disease, where both genetic and environmental factors have significant roles in pathogenesis. As regard asthma pathogenesis, the chemokine/chemokine receptor system is considered a key point of the immune response in most allergic diseases. This study was done to estimate the prevalence of bronchial asthma among school age children and explore the association between the underlying gene polymorphisms in chemokine receptor 3 (CCR3) and symptom-based clinical asthma phenotypes among a cohort of Egyptian children.

Results

Prevalence of asthma is increasing (20.6%). There are male asthma predominance. Family history of bronchial asthma and allergic diseases are predominant risk factors for asthma development. Sixty asthmatic cases with different clinical phenotypes were compared to 100 healthy controls, results explored that eosinophilic percent and total serum IgE are significantly higher among asthmatic cases versus controls. There are no significant difference regarding eosinophilic percent, serum IgE, and CCR3 T51C gene polymorphism among different clinical asthma phenotypes. There is no significant difference as regards degree of severity of asthma and level of asthma control between CCR3 T51C gene polymorphism.

Conclusion

We conclude the prevalence of bronchial asthma is increasing. Also, eosinophilic percent and serum IgE are elevated in asthma patients, while CCR3 T51C gene polymorphism frequency seemed to be more prevalent among asthmatic subjects however without statistical significance. We recommend a prospective study on larger sample size to validate our results.
Correlation between severity of pulmonary embolism and obstructive sleep apnea using computed tomography pulmonary artery obstruction index and right ventricular to left ventricular diameter ratio as severity indices
Authors: Makboul Marwa , Magdy Doaa M. , Metwally Ahmed , Farghaly Shimaa
Published: September 2023

Background

Recent studies have shown a bidirectional association between pulmonary embolism (PE) and obstructive sleep apnea (OSA), and due to their morbidity and mortality, this contributes significantly to the global health-care burden, so this study aims to assess the relationship between PE and OSA severity using the obstruction index of the pulmonary artery and the ratio of right ventricular to left ventricular (RV/LV) diameter as severity indices.

Results

The study comprised 138 patients with a high clinical suspicion of PE that was verified by computed tomography pulmonary angiography. In addition to calculating the RV/LV diameter ratio and pulmonary artery obstruction index (PAOI), the pulmonary embolism severity index was also calculated, and the Epworth Sleepiness Scale and polysomnography (PSG) were used to assess all patients for OSA. Finally, three groups of patients (< 15% vs. 15–50% vs. > 50%) were created based on the PAOI. Age, gender, neck, and waist circumference showed no significant difference between the three groups, but there were significant correlations between higher PAOI and increased BMI, provoked PE, increased rate of thrombolysis, increase in the recurrence of venous thrombosis, a longer length of hospital stay, and a higher ratio of RV/LV diameter (p value was < 0.05). Regarding PSG, a significant positive correlation was observed between the apnea–hypopnea index (AHI) and higher PAOI as well as the ratio of RV/LV diameter (r = 0.957, p value < 0.001) and (r = 0.825, p value < 0.001), respectively, with the obstruction index of the pulmonary artery > 40%, and the ratio of RV/LV diameter > 1 being found to be predictors of severe sleep apnea.

Conclusions

We deduced from this study that there is a substantial relationship between the severity of PE and the severity of OSA, as patients with higher obstruction of the pulmonary artery had severe OSA, and both the obstruction index of the pulmonary artery > 40% and the ratio of RV/LV diameter > 1 were considered significant predictors for the severity of OSA among the acute PE patients.
Correlation of placental thickness with gestational age in second and third trimester using ultrasonography
Authors: Vinchurkar Kshitija Narayan , Aiyappan Senthil Kumar , Prem Kumar C. , Shanmugam Vinayagam , Singh Aparajita
Published: September 2023

Background

The accuracy of currently established parameters in estimating gestational age decreases as pregnancy advances. With advancing gestational age, there is an expected linear increase in placental thickness. Placental thickness may thus be used to reliably predict gestational age, especially in later stages.

Aim

Our study aimed to determine the relationship between placental thickness and gestational age and routinely used fetal growth parameters in the second and third trimesters. Additionally, we aimed to see if the placental thickness was lower in small for gestational fetuses.

Methods

This study was performed at a tertiary care center and was a prospective observational study. We recruited consecutive 200 pregnant women fulfilling inclusion and exclusion criteria. Using routine antenatal ultrasonography, we obtained several measurements of placental thickness, BPD, HC, FL, and AC. The placental thickness was measured at the level of umbilical cord insertion. The gestational age was calculated using last menstrual period.

Results

There was a strong correlation between placental thickness and gestational age (p < 0.001), BPD (p < 0. 001), HC (p < 0. 001), FL (p < 0. 001), and AC (p < 0.001) in both trimesters combined. In the second trimester, there was a strong correlation between placental thickness and gestational age (p < 0.001), BPD (p < 0.01), HC (p < 0.001), and AC (p < 0.001). In the third trimester, there was a strong correlation between placental thickness and gestational age (p < 0.001), BPD (p < 0.001), HC (p < 0.001), FL (p < 0.001) and AC (p < 0. 001). Patients delivering Small for gestational age (SGA) babies had significantly thinner placentas as compared to those with normal-weight babies (p < 0.001).

Conclusions

Placental thickness has a strong correlation with gestation age as well as BPD, HC, and AC in the second and third trimesters. Placental thickness is significantly lower in small for gestational age babies. Routine measurement of antenatal placental thickness using ultrasound can help predict gestational age and detect small for gestational age babies.
Estimating Treatment Effect of Adjuvant Chemotherapy in Elderly Patients With Stage III Colon Cancer Using Bayesian Networks
Authors: Sieswerda Melle , van Rossum Ruby , Bermejo Inigo , Geleijnse Gijs , Aben Katja , van Erning Felice , de Hingh Ignace , Lemmens Valery , Dekker André , Verbeek Xander
Published: September 2023

Advanced statistical analysis (with BNs) suggests that oxaliplatin should be avoided in elderly patients.
Distinct Pattern of Membrane Formation With Spinal Cerebrospinal Fluid Leaks in Spontaneous Intracranial Hypotension
Authors: Häni Levin , Fung Christian , El Rahal Amir , Volz Florian , Kraus Luisa Mona , Schnell Oliver , Ferrarese Roberto , Erny Daniel , Schwabenland Marius , Urbach Horst , Lützen Niklas , Beck Jürgen
Published: September 2023

BACKGROUND AND OBJECTIVES:

To systematically describe pertinent, intraoperative anatomic findings encountered when approaching spinal cerebrospinal fluid (CSF) leaks and CSF-venous fistulas in spontaneous intracranial hypotension (SIH).

METHODS:

In a retrospective study, we included surgically treated patients suffering from SIH at our institution from April 2018 to March 2022. Anatomic, intraoperative data were extracted from operative notes and supplemented with data from surgical videos and images. Prominent anatomic features were compared among different types of CSF leaks.

RESULTS:

The study cohort consists of 120 patients with a mean age of 45.2 years. We found four distinct patterns of spinal membranes specifically associated with different types of CSF leaks: (i) thick, dorsal membranes, which were hypervascular and may mimic the dura (pseudodura); (ii) thin, lateral membranes encapsulating a ventral epidural CSF compartment (confining the spinal longitudinal extradural CSF collection); (iii) ventral membranes constituting a transdural funnel–like CSF channel; and (iv) lateral membranes forming spinal cysts/meningeal diverticulae associated with lateral CSF leaks. The latter three types resemble a layer of arachnoid herniated through the dural defect.

CONCLUSION:

We describe four distinct spinal (neo-)membranes in association with spinal CSF leaks. Formation of these membranes, or emergence by herniation of arachnoid through a dural defect, constitutes a specific pathoanatomic feature of patients with SIH and CSF leaks. Recognition of these membranes is of paramount importance for diagnosis and treatment of patients with spinal CSF leaks.
Whole-joint histogram analysis of different models of diffusion weighted imaging in evaluating disease activity of axial spondyloarthritis
Authors: Xie Ruyi , Liang Xiaoqing , Zhang Xiaoli , Morelli John N , Wang Jingyi , Liu Chanyuan , Li Xiaoming
Published: September 2023

Objectives

To assess whole-joint histogram analysis of mono-exponential and bi-exponential diffusion weighted and diffusion kurtosis imaging in evaluating disease activity of axial spondyloarthritis (axSpA).

Methods

A total of 82 patients with axSpA who underwent both DKI and multi b diffusion weighted imaging of the sacroiliac joints were divided into active and inactive disease groups based on clinical activity indices. Another 17 patients with nonspecific low back pain were included as a control group. The SPARCC scoring system was used to assess the level of sacroiliac joint bone marrow edema. Histogram parameters of apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion fraction (f), pseudodiffusion coefficient (D*), mean kurtosis (MK), and mean diffusivity (MD) were calculated. Regions of interest were placed covering the entire sacroiliac joint. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of imaging parameters in distinguishing different groups. Regression analysis was applied to determine the correlation between imaging parameters and clinical activity indices.

Results

All of the histogram parameters distinguished the active from inactive groups with a low area under the curve (AUC) (max AUCs≤0.71), while the SPARCC score failed to differentiate the two groups (p = 0.08). MD, MK, D, D*, and ADC showed good performance in differentiating active and inactive from control groups (max AUC = 0. 81 ~ 0.98). f50 differentiated the active from control groups with an AUC of 0.72, significantly lower than the maximum AUC for MD, MK, D, ADC, and SPARCC score (all p < 0.05). The max AUC of MD in differentiating inactive from control groups was significantly higher than that of D* and the SPARCC score. MD, D, D*, f, and ADC were positively correlated with BASDAI, while MK was negatively correlated with BASDAI. Only MD was positively correlated with hsCRP.

Conclusions

Whole-joint histogram analysis of mono-exponential, bi-exponential diffusion weighted, and diffusion kurtosis imaging showed good diagnostic performance in differentiating active and inactive axSpA from patients with non-specific back pain. All the imaging parameters were correlated with BASDAI except for SPARCC score. Only DKI-derived MD was correlated with an increase in hsCRP, suggesting its potential use as an imaging biomarker for disease activity in axSpA.

Advances in knowledge

1. No significant difference was found between the three models of diffusion weighted imaging in evaluating disease activity of axial spondyloarthritis.

2. Only DKI-derived MD was correlated with an increase in hsCRP, suggesting its potential use as an imaging biomarker for disease activity in axSpA.
Radiotherapy of orbital metastases: a systematic review of management and treatment outcomes on behalf of palliative care study group of Italian association of radiotherapy and clinical oncology (AIRO)
Authors: Pezzulla Donato , Di Franco Rossella , Zamagni Alice , Pastore Francesco , Longo Silvia , Dominici Luca , Lillo Sara , Ciabattoni Antonella , Arcidiacono Fabio , Deodato Francesco , Muto Paolo , Morganti Alessio Giuseppe , Cellini Francesco , Maranzano Ernesto
Published: September 2023

Objectives:

We search the current literature on data regarding the role of RT in OM treatment, focusing on the improvement of symptoms and patient quality of life.

Methods:

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations.

Results:

From 340 citations, 60 papers were finally selected: 45 case reports and 15 case series. The case reports accounted for 47 patients. In 37/39 cases (95%), EBRT was done. Patients were mainly treated with 3DCRT, IMRT, and with SBRT. The most used RT regimens were 30 Gy in 10 fractions (23%) and 20–25 Gy in 5 fx (13%). No sever toxicity was reported. A median LC of 11 months (range 1–54 months) and a median OS of 12 months (range 1–54 months) were registered. Among the case series, a total of 457 patients were examined, 227 of whom underwent RT. The main used techniques were 3DCRT, CK, GK, SBRT, and BRT. RT doses could vary from 30 Gy/10 fractions to 60 Gy/30 fractions, 50 Gy/5 fractions, or 16.5–21 Gy in single fraction. No toxicity above G2 was reported. ORR could vary between 75 and 100%. Only two study provided information on response duration: a mean LC time of 22.8 months and a mean time to local progression of 5 months (range: 3–7). Regarding OS, the data were heterogeneous, ranging between 1 and 54 months.

Conclusions:

RT for OM seems to be a safe and feasible option. More information on the RT ideal techniques and dose are still needed.

Advances in knowledge:

This paper tried to sum up the few and fragmented data on the use of radiotherapy for orbital metastases: the possible option ranged from 3D- and 2D-CRT to SBRT, CK, and GK, with different possible fractionations (30Gy in 10 fractions, 60 Gy/30 fractions, 20-50 Gy/5 fractions, or 16.5-21 Gy in single fraction). Regardless of the chosen approach, almost all treated patients experienced a benefit after RT in terms of OM-related symptom intensity reduction and a good acute and late toxicity profile.