bluuebunny/crossref_metadata_2025 huggingface dataset:
Polypharmacy in Older Adults Undergoing Major Surgery: Prevalence, Association With Postoperative Cognitive Dysfunction and Potential Associated Anesthetic Agents
Authors: Lertkovit Saranya , Siriussawakul Arunotai , Suraarunsumrit Patumporn , Lertpipopmetha Wanicha , Manomaiwong Natapong , Wivatdechakul Wittachi , Srinonprasert Varalak
Published: February 2022

Background

Polypharmacy, which is defined as the use of 5 or more medications, can exert significant adverse impact on older adult patients. The objective of this study was to determine the prevalence of polypharmacy, and to investigate its association with postoperative cognitive dysfunction (POCD) in older adult patients who underwent elective major surgery at Siriraj Hospital—Thailand's largest national tertiary referral center.

Methods

This prospective study included older adult patients aged ≥65 years who were scheduled for elective major surgery during December, 2017 to December, 2019 study period. Patient demographic, sociodemographic, anthropometric, clinical, comorbidity, anesthetic, surgical, and medication data were collected and compared between the polypharmacy and non-polypharmacy groups. Postoperative cognitive dysfunction (POCD) was diagnosed in patients with at least a 2-point decrease in their Montreal Cognitive Assessment score after surgery. Multivariate logistic regression analysis was used to identify independent predictors of POCD.

Results

A total of 250 patients (141 males, 109 females) with an average age of 72.88 ± 6.93 years were included. The prevalence of polypharmacy was 74%. Preoperative data showed the polypharmacy group to be more likely to be receiving potentially inappropriate medications, to be scheduled for cardiovascular thoracic surgery, and to have more comorbidities. There was a non-significant trend in the association of polypharmacy and POCD (crude odds ratio (OR): 2.11, 95% confidence interval [CI]: 0.90–4.94; p = 0.08). Benzodiazepine, desflurane, or isoflurane administration during surgery were all significantly associated with POCD in univariate analysis. Multivariate analysis revealed intraoperative benzodiazepine (adjusted OR [aOR]: 2.24, 95% CI: 1.10–4.68; p = 0.026) and isoflurane (aOR: 2.80, 95% CI: 1.35–5.81; p = 0.006) as two independent variables associated with the development of POCD. Desflurane was found to be a protective factor for POCD with a crude OR of 0.17 (95% CI: 0.03–0.74, p = 0.019); however, independent association was not found in multivariate analysis.

Conclusion

There was a high prevalence of polypharmacy in this study; however, although close (p = 0.08), significant association was not found between polypharmacy and POCD. Benzodiazepine and isoflurane were both identified as independent predictors of the development of POCD among older adult patients undergoing elective major surgery, especially among those classified as polypharmacy.
Early and Regular Bronchoscopy Examination on Effect of Diagnosis and Prognosis for Patients With Tracheobronchial Tuberculosis
Authors: Hu Tingting , Li Yishi , Wang Xiaohui , Chen Yan , Nie Xiao , Zhuang Rongjuan , Li Ying , Guo Shuliang
Published: February 2022

Background

Bronchoscopy is the main method for the diagnosis of tracheobronchial tuberculosis (TBTB). However, it is not well-used in patients with pulmonary tuberculosis (PTB), leading to misdiagnosis. The aim of this study is to verify the value and feasibility of bronchoscopy for an early diagnosis and treatment of TBTB.

Materials and Methods

A prospective observational study was performed in patients with active PTB. The ratios of TBTB and tracheobronchial stenosis were analyzed with propensity score matching (PSM) for baseline characteristics, and a Cox regression model was further employed to adjust for residual confounding factors.

Results

A total of 656 patients with active PTB were enrolled in the study that included 307 patients in the active group and 349 patients in the non-active group. The ratio of TBTB was significantly higher in the active group than that in the non-active group [hazard ratio (HR), 2.31; 95% CI, 1.70–3.14; p < 0.001]. With PSM, the proportion of tracheobronchial stenosis in the non-active group was significantly higher than that in the active group (HR, 1.84; 95% CI, 1.15–2.95; p = 0.011). Moreover, the number of patients with moderate to severe stenosis were significantly higher than that in the active group (HR, 4.13; 95% CI, 2.25–7.63; p < 0.001). Similar results were obtained with multivariate analysis. With 12 months of treatment, both therapeutic effective rate (84.7 vs. 68.2%; p = 0.009) and improvement rate of non-fibrotic tracheobronchial stenosis (79.1 vs. 47.4%; p = 0.022) were higher in the active group than that in the non-active group.

Conclusion

Active and regular bronchoscopy is conducive to early diagnosis of TBTB, combined with prompt anti-tuberculosis therapy, greatly reducing the occurrence of tracheobronchial stenosis and improving prognosis.
Comparative Analysis of Intestinal Microflora Between Two Developmental Stages of Rimicaris kairei, a Hydrothermal Shrimp From the Central Indian Ridge
Authors: Qi Li , Lian Chun-Ang , Zhu Fang-Chao , Shi Mengke , He Li-Sheng
Published: February 2022

Despite extreme physical and chemical characteristics, deep-sea hydrothermal vents provide a place for fauna survival and reproduction. The symbiotic relationship of chemotrophic microorganisms has been investigated in the gill of Rimicaris exoculata, which are endemic to the hydrothermal vents of the Mid-Atlantic Ridge. However, only a few studies have examined intestinal symbiosis. Here, we studied the intestinal fauna in juvenile and adult Rimicaris kairei, another species in the Rimicaris genus that was originally discovered at the Kairei and Edmond hydrothermal vent fields in the Central Indian Ridge. The results showed that there were significant differences between juvenile and adult gut microbiota in terms of species richness, diversity, and evenness. The values of Chao1, observed species, and ASV rarefaction curves indicated almost four times the number of species in adults compared to juveniles. In juveniles, the most abundant phylum was Deferribacterota, at 80%, while in adults, Campilobacterota was the most abundant, at 49%. Beta diversity showed that the intestinal communities of juveniles and adults were clearly classified into two clusters based on the evaluations of Bray–Curtis and weighted UniFrac distance matrices. Deferribacteraceae and Sulfurovum were the main featured bacteria contributing to the difference. Moreover, functional prediction for all of the intestinal microbiota showed that the pathways related to ansamycin synthesis, branched-chain amino acid biosynthesis, lipid metabolism, and cell motility appeared highly abundant in juveniles. However, for adults, the most abundant pathways were those of sulfur transfer, carbohydrate, and biotin metabolism. Taken together, these results indicated large differences in intestinal microbial composition and potential functions between juvenile and adult vent shrimp (R. kairei), which may be related to their physiological needs at different stages of development.
Impacts of the Biocontrol Strain Pseudomonas simiae PICF7 on the Banana Holobiont: Alteration of Root Microbial Co-occurrence Networks and Effect on Host Defense Responses
Authors: Gómez-Lama Cabanás Carmen , Wentzien Nuria M. , Zorrilla-Fontanesi Yasmín , Valverde-Corredor Antonio , Fernández-González Antonio J. , Fernández-López Manuel , Mercado-Blanco Jesús
Published: February 2022

The impact of the versatile biocontrol and plant-growth-promoting rhizobacteria Pseudomonas simiae PICF7 on the banana holobiont under controlled conditions was investigated. We examine the fate of this biological control agent (BCA) upon introduction in the soil, the effect on the banana root microbiota, and the influence on specific host genetic defense responses. While the presence of strain PICF7 significantly altered neither the composition nor the structure of the root microbiota, a significant shift in microbial community interactions through co-occurrence network analysis was observed. Despite the fact that PICF7 did not constitute a keystone, the topology of this network was significantly modified—the BCA being identified as a constituent of one of the main network modules in bacterized plants. Gene expression analysis showed the early suppression of several systemic acquired resistance and induced systemic resistance (ISR) markers. This outcome occurred at the time in which the highest relative abundance of PICF7 was detected. The absence of major and permanent changes on the banana holobiont upon PICF7 introduction poses advantages regarding the use of this beneficial rhizobacteria under field conditions. Indeed a BCA able to control the target pathogen while altering as little as possible the natural host-associated microbiome should be a requisite when developing effective bio-inoculants.
Bowel Movement: Integrating Host Mobility and Microbial Transmission Across Host Taxa
Authors: Weinhold Arne
Published: February 2022

The gut microbiota of animals displays a high degree of plasticity with respect to environmental or dietary adaptations and is shaped by factors like social interactions, diet diversity or the local environment. But the contribution of these drivers varies across host taxa and our ability to explain microbiome variability within wild populations remains limited. Terrestrial animals have divergent mobility ranges and can either crawl, walk or fly, from a couple of centimeters toward thousands of kilometers. Animal movement has been little regarded in host microbiota frameworks, though it can directly influence major drivers of the host microbiota: (1) Aggregation movement can enhance social transmissions, (2) foraging movement can extend range of diet diversity, and (3) dispersal movement determines the local environment of a host. Here, I would like to outline how movement behaviors of different host taxa matter for microbial acquisition across mammals, birds as well as insects. Host movement can have contrasting effects and either reduce or enlarge spatial scale. Increased dispersal movement could dissolve local effects of sampling location, while aggregation could enhance inter-host transmissions and uniformity among social groups. Host movement can also extend the boundaries of microbial dispersal limitations and connect habitat patches across plant-pollinator networks, while the microbiota of wild populations could converge toward a uniform pattern when mobility is interrupted in captivity or laboratory settings. Hence, the implementation of host movement would be a valuable addition to the metacommunity concept, to comprehend microbial dispersal within and across trophic levels.
Antiviral Effect of Selenomethionine on Porcine Deltacoronavirus in Pig Kidney Epithelial Cells
Authors: Ren Zhihua , Jia Guilin , He Hongyi , Ding Ting , Yu Yueru , Zuo ZhiCai , Hu Yanchun , Zhong Zhijun , Yu Shumin , Deng Huidan , Shen Liuhong , Cao Suizhong , Peng Guangneng , Wang Ya , Cai Dongjie , Gou Liping , Ma Xiaoping , Liu Haifeng , Zhou Ziyao , Deng Youtian , Yang Dingyong , Deng Junliang
Published: February 2022

Porcine deltacoronavirus (PDCoV) is an emerging porcine intestinal coronavirus in recent years, which mainly causes different degrees of vomiting and diarrhea in piglets and has caused great harm to the swine husbandry worldwide since its report. Selenium is an essential trace element for organisms and has been demonstrated to have antiviral effects. In this study, pig kidney epithelial (LLC-PK) cells were used to study the antiviral activity of selenomethionine (Se-Met) (2, 4, 8, and 16 μM) against PDCoV by detecting the replication of the virus, the expression of the mitochondrial antiviral signal protein (MAVS) protein, and the phosphorylation of interferon regulatory factor-3 (IRF-3), IFN-α, and IFN-β, and the changes in glutathione content, glutathione peroxidase, superoxide dismutase activity, and hydrogen peroxide content in the cells. The results showed that Se-Met at higher than physiological concentrations (16 μM) could significantly inhibit the replication of PDCoV in LLC-PK cells and enhance the expression of MAVS protein and the phosphorylation of IRF-3. In addition, Se-Met also improved the intracellular production of IFNα/β and antioxidant capacity with increasing doses. These data suggest that the availability of selenium through selenomethionine supports the antiviral response in porcine kidney cells, and the specific mechanism is attributed to the improved cellular antioxidant capacity and activation of the MAVS pathway by Se-Met.
Dynamic Control Balancing Cell Proliferation and Inflammation is Crucial for an Effective Immune Response to Malaria
Authors: Gupta Anuj , Galinski Mary R. , Voit Eberhard O.
Published: February 2022

Malaria has a complex pathology with varying manifestations and symptoms, effects on host tissues, and different degrees of severity and ultimate outcome, depending on the causative Plasmodium pathogen and host species. Previously, we compared the peripheral blood transcriptomes of two macaque species (Macaca mulatta and Macaca fascicularis) in response to acute primary infection by Plasmodium knowlesi. Although these two species are very closely related, the infection in M. mulatta is fatal, unless aggressively treated, whereas M. fascicularis develops a chronic, but tolerable infection in the blood. As a reason for this stark difference, our analysis suggests delayed pathogen detection in M. mulatta followed by extended inflammation that eventually overwhelms this monkey’s immune response. By contrast, the natural host M. fascicularis detects the pathogen earlier and controls the inflammation. Additionally, M. fascicularis limits cell proliferation pathways during the log phase of infection, presumably in an attempt to control inflammation. Subsequent cell proliferation suggests a cell-mediated adaptive immune response. Here, we focus on molecular mechanisms underlying the key differences in the host and parasite responses and their coordination. SICAvar Type 1 surface antigens are highly correlated with pattern recognition receptor signaling and important inflammatory genes for both hosts. Analysis of pathogen detection pathways reveals a similar signaling mechanism, but with important differences in the glutamate G-protein coupled receptor (GPCR) signaling pathway. Furthermore, differences in inflammasome assembly processes suggests an important role of S100 proteins in balancing inflammation and cell proliferation. Both differences point to the importance of Ca2+ homeostasis in inflammation. Additionally, the kynurenine-to-tryptophan ratio, a known inflammatory biomarker, emphasizes higher inflammation in M. mulatta during log phase. Transcriptomics-aided metabolic modeling provides a functional method for evaluating these changes and understanding downstream changes in NAD metabolism and aryl hydrocarbon receptor (AhR) signaling, with enhanced NAD metabolism in M. fascicularis and stronger AhR signaling in M. mulatta. AhR signaling controls important immune genes like IL6, IFNγ and IDO1. However, direct changes due to AhR signaling could not be established due to complicated regulatory feedback mechanisms associated with the AhR repressor (AhRR). A complete understanding of the exact dynamics of the immune response is difficult to achieve. Nonetheless, our comparative analysis provides clear suggestions of processes that underlie an effective immune response. Thus, our study identifies multiple points of intervention that are apparently responsible for a balanced and effective immune response and thereby paves the way toward future immune strategies for treating malaria.
The Emesis Trial: Depressive Glioma Patients Are More Affected by Chemotherapy-Induced Nausea and Vomiting
Authors: Dufner Vera , Kessler Almuth Friederike , Just Larissa , Hau Peter , Bumes Elisabeth , Pels Hendrik Johannes , Grauer Oliver Martin , Wiese Bettina , Löhr Mario , Jordan Karin , Strik Herwig
Published: February 2022

Purpose

Glioma patients face a limited life expectancy and at the same time, they suffer from afflicting symptoms and undesired effects of tumor treatment. Apart from bone marrow suppression, standard chemotherapy with temozolomide causes nausea, emesis and loss of appetite. In this pilot study, we investigated how chemotherapy-induced nausea and vomiting (CINV) affects the patients' levels of depression and their quality of life.

Methods

In this prospective observational multicentre study (n = 87), nausea, emesis and loss of appetite were evaluated with an expanded MASCC questionnaire, covering 10 days during the first and the second cycle of chemotherapy. Quality of life was assessed with the EORTC QLQ-C30 and BN 20 questionnaire and levels of depression with the PHQ-9 inventory before and after the first and second cycle of chemotherapy.

Results

CINV affected a minor part of patients. If present, it reached its maximum at day 3 and decreased to baseline level not before day 8. Levels of depression increased significantly after the first cycle of chemotherapy, but decreased during the further course of treatment. Patients with higher levels of depression were more severely affected by CINV and showed a lower quality of life through all time-points.

Conclusion

We conclude that symptoms of depression should be perceived in advance and treated in order to avoid more severe side effects of tumor treatment. Additionally, in affected patients, delayed nausea was most prominent, pointing toward an activation of the NK1 receptor. We conclude that long acting antiemetics are necessary totreat temozolomide-induced nausea.
The Efficacy and Safety of Cilostazol vs. Aspirin for Secondary Stroke Prevention: A Systematic Review and Meta-Analysis
Authors: Chai Erqing , Chen Jinhua , Li Changqing , Zhang Xue , Fan Zhiqiang , Yang Shijie , Zhao Kaixuan , Li Wei , Xiao Zaixing , Zhang Yichuan , Tang Futian
Published: February 2022

Background

Cilostazol is often used in Asia-Pacific countries for stroke prevention. The current systematic review and meta-analysis aimed to evaluate the effectiveness, safety, and adverse outcomes of cilostazol monotherapy compared to aspirin monotherapy for secondary stroke prevention.

Methods

The researchers conducted a comprehensive research in multiple databases (PubMed, Embase, and Cochrane library) of randomized controlled trials from conception to December 2020. The primary efficacy outcome was the occurrence of any stroke, the primary safety outcome was the bleeding risk, and the primary adverse outcome was the rate of headache and dizziness. The Mantel-Haenszel method was used to calculate a random-effects prediction. Cilostazol and aspirin were compared using a pooled risk assessment with 95% CIs.

Results

Six studies involving 5,617 patients were included in this review. Compared with aspirin monotherapy, cilostazol was associated with significantly lower rates of any strokes (RR: 0.67; 95% CI: 0.55–0.82) and significantly lower bleeding rates [risk ratio (RR): 0.53; 95% CI: 0.37–0.74]. However, compared with aspirin monotherapy, cilostazol was associated with significantly higher rates of headache (RR: 1.77; 95% CI: 1.41–2.20) and dizziness (RR: 1.28; 95% CI: 1.08–1.52).

Conclusions

Consistent with previous studies, cilostazol monotherapy is superior to aspirin monotherapy in reducing the rate of any strokes and the bleeding risk after having a stroke. However, the use of cilostazol monotherapy is associated with several adverse life outcomes such as headaches and dizziness.
The Effect of Verbal Task Instruction on Spatial-Numerical Associations of Response Codes Effect Coding of Spatial-Numerical Associations: Evidence From Event-Related Potential
Authors: Pan Yun , Zhang Zhiwei , Li Wei , Zhao Xiaoxiao
Published: February 2022

The spatial-numerical associations of response codes (SNARC) effect reveals that individuals can represent numbers spatially. In this study, event-related potential (ERP) technology was used to probe the effect of verbal-spatial task instructions on spatial-numerical association coding by using digit parity and magnitude judgment tasks, with the numbers 1–9 (except 5) and Chinese word labels (“left” and “right”) as experimental materials. The behavioral results of Experiment 1 showed that the SNARC effect was mainly based on verbal-spatial coding and appeared when the stimulus onset asynchrony (SOA) between the presentation of the verbal labels and the target digit was 0 ms. ERP results did not reveal any significant SNARC-related effects in either the N1 or P3 components. The behavioral results of Experiment 2 again showed that the SNARC effect was dominated by verbal-spatial coding. ERP results showed that significant effects related to verbal-spatial coding were found in both the early positive deflection of the stimulus-locked lateralized readiness potential (S-LRP) and the latency of the response-locked LRP (R-LRP). Hence, in this study, the nature of the spatial coding of the digit magnitudes was influenced by the processing of the word labels and affected both the response selection and response preparation stages.
Associations Between 25-Hydroxyvitamin D, Kidney Function, and Insulin Resistance Among Adults in the United States of America
Authors: Geng Jiwen , Qiu Yuxuan , Li Yupei , Li Jiameng , Liao Ruoxi , Du Heyue , Jiang Luojia , Wang Liya , Qin Zheng , Yang Qinbo , Yu Qiao , Zhang Zhuyun , Su Baihai
Published: February 2022

Background

Although many molecular studies have tried to explore the relationship between vitamin D metabolism and kidney function, the association between 25-hydroxyvitamin D [25(OH)D] and kidney function is still controversial. Previous studies reported that low vitamin D status and decreased kidney function were associated with insulin resistance (IR). However, neither of them was confirmed by large population-based studies. This study evaluated the associations between 25(OH)D and kidney function and the associations between both of them and IR among adults in the United States of America (USA).

Methods

We analyzed 36,523 adults from the National Health and Nutrition Examination Survey (NHANES) (2001–2014). Kidney function was assessed by the estimated glomerular filtration rate (eGFR), and IR was assessed by homeostasis model assessment (HOMA-IR). All data were survey-weighted, and corresponding linear regression models were performed to examine the associations.

Results

The mean serum 25(OH)D levels were found to be increased in participants with decreased kidney function (eGFR <90 ml/min/1.73 m2), and each unit of decreased serum 25(OH)D concentrations predicted 0.453 ml/min/1.73 m2 (95% CI: 0.426 to 0.480, p < 0.0001) higher eGFR. In addition, each unit of decreased eGFR was associated with 0.007 higher HOMA-IR, while each unit of decreased 25(OH)D concentrations led to 0.025 higher HOMA-IR.

Conclusions

Serum 25-hydroxyvitamin D concentrations were negatively associated with kidney function. IR appears in the early stage of kidney dysfunction, and both serum 25(OH)D concentrations and kidney function are negatively associated with IR. Clinicians should maintain appropriate serum 25(OH)D concentrations and doses of vitamin D supplements for different populations. The underlying mechanism of these associations still needs more research, especially the negative association between serum 25(OH)D concentrations and kidney function.
Effects of Koumiss on Intestinal Immune Modulation in Immunosuppressed Rats
Authors: Li Qinyu , Zhang Chunjie , Xilin Tuya , Ji Mingyue , Meng Xiangxi , Zhao Yulian , Siqin Bateer , Zhang Na , Li Minhui
Published: February 2022

Koumiss is a traditional fermented dairy product with health and medicinal benefits. It is very popular in the Inner Mongolia Autonomous Region of China. The results of relevant studies have shown that koumiss can regulate the gastrointestinal environment, improve the absorption of nutrients, improve the body's intolerance to lactose, enhance the body's immunity, prevent scurvy and atherosclerosis, and aid in the treatment of tuberculosis. However, there are no systematic reports on the effects of koumiss on immunity. In this study, we aimed to decipher the effects of koumiss on intestinal immune modulation. We used liquid chromatography-tandem mass spectrometry (LC-MS) analysis to determine the composition of Koumiss. Using Compound Discoverer software, we compared the mass spectrometry data with the compound information in the online databases ChemSpider and mzCloud to intelligently identify the main chemical components of koumiss. Additionally, we used Mass Frontier small molecule fragmentation libraryTM to determine the structure of fragment ions. A total of 21 components were identified, which clarified the chemical basis of koumiss. These 21 compounds were then used to perform molecular docking with immune-related targets, such as TNF, IL2, IL10, etc. The results indicated good docking activity between most of the compounds and the targets. Then, an immunosuppressive rat model was used to determine the therapeutic effect of koumiss. The results of this study showed that koumiss could, to a certain extent, correct the atrophy of the thymus and spleen in immunosuppressed model rats. The number of leukocytes, lymphocytes, and the CD4+/CD8+ ratio of peripheral blood lymphocytes was also increased. In addition, it could effectively improve the structure of the small intestinal mucosa, which shows that koumiss has a positive effect on the intestinal immune function of immunosuppressed rats. These findings provide an experimental basis for the development and utilization of koumiss as a therapeutic product.
Novel Process Methods for the Whole Cottonseed: Effect on the Digestibility, Productivity, Fat Profile, and Milk Gossypol Levels in Lactating Dairy Cows
Authors: Sun Xiaoge , Su Yitong , Hao Yangyi , Zhang Jun , Yue Xiaomei , Wang Wei , Ma Zhu , Chu Kangkang , Wang Shuang , Wang Yajing , Li Shengli
Published: February 2022

In this study, we aimed to determine the effect of mixed-process methods on the ruminal degradability of whole cottonseed (WCS) both in situ and in vitro, and the effect on the production performance of dairy cows. Eight WCS process methods were tested on the ruminal digestibility, including crush-alkali 1 (CA1), crush-alkali 2 (CA2), crush-alkali 3 (CA3), alkali 1-crush (A1C), alkali 2-crush (A2C), alkali 3-crush (A3C), crush-only (CO), and non-processed. Alkali 1, 2, and 3 indicate the supplementation of alkali to WCS at the dose of 4% on dry matter (DM) base as followed: 4% NaOH, 2% NaOH + 2% CaO, and 2% NaOH + 2% CaCl2 alkaline, respectively. Among all treatments, CA2 showed the highest WCS ruminal degradation in situ and the highest intestinal digestibility of WCS in vitro. Furthermore, an animal experiment was conducted for 60 days on 30 Holstein dairy cows, using a diet without WCS (CON group), a diet containing 8% non-processed WCS (NP group), and a diet containing 8% CA2-treated WCS (CA2 group). The results indicated that the dry matter intake, 4% fat-corrected milk production, milk protein, milk fat, and content of short-chain saturated fatty acid of milk in the CA2 group were significantly higher (P < 0.05) than CON group. Furthermore, DMI, the CLA was significantly greater (P < 0.05) in the CA2 group than the other groups. Additionally, the free gossypol concentration in serum or milk was under safety level in the three groups. Overall, crush and alkalization (NaOH: CaO = 1:1) treatment could improve the utilization of WCS in dairy farms.
Advances in Phenotyping Obesity and in Its Dietary and Pharmacological Treatment: A Narrative Review
Authors: Pujia Roberta , Tarsitano Maria Grazia , Arturi Franco , De Lorenzo Antonino , Lenzi Andrea , Pujia Arturo , Montalcini Tiziana
Published: February 2022

In recent times, it has become evident that there are individuals who, from a metabolic point of view, are affected by obesity but have a normal body mass index. There are also metabolically healthy individuals with a high body mass index who are thus are considered as to be affected by obesity obese. Understanding that individuals with obesity are phenotypically heterogeneous is a relatively novel concept which, although present in the scientific literature, unfortunately has not yet had an impact in clinical practice. However, common dietary approaches are not effective in treating large numbers of obese patients with obesity. This narrative review, based on the material searched via PubMed and the Web of Science up to October 2021, proposes a downsizing of the role of the body mass index in identifying the individual with “true obesity” since it is only partially useful, and suggests a new approach which also integrates the body composition and assessment of metabolic parameters. This approach leads to personalized therapies that work best for each obesity phenotype in reducing the risk of non-communicable diseases.
Accelerators, Gantries, Magnets and Imaging Systems for Particle Beam Therapy: Recent Status and Prospects for Improvement
Authors: Collings Edward W. , Lu Lanchun , Gupta Nilendu , Sumption Mike D.
Published: February 2022

The paper begins by emphasizing the clinical and commercial importance of proton or other charged particle such as carbon ion therapy, refers to the manufacturers of such systems of which more than 120 are installed or under construction worldwide by April 2021. A general review of charged particle therapy systems refers to six manufacturers and provides in tabular form some details of systems installed in the US, Europe, Asia, and elsewhere. In a description of the principles of particle beam therapy a comparison is made of the properties of photons (x-rays) versus protons and protons versus carbon ions. A brief discussion of accelerators in general is followed by descriptions of cyclotrons (including the isosynchronous cyclotron and the synchrocyclotron) and synchrotrons. An interesting case study describes the evolution of a normal-conducting 220 ton cyclotron into an iron-free synchrocyclotron weighing only 5 tons. The general principles of beam handling and gantry design are described. Subsequent sections describe gantry magnets in detail - normal conducting gantry magnets, superconducting gantry magnets for proton- and carbon therapy. Mention is made of a novel CERN-designed superconducting toroidal gantry for hadron therapy, GaToroid. This device, operating under steady state current and magnetic field, is able to deliver a beam at discrete angles over a range of treatment energies. Also considered are low temperature superconducting (LTS) and high temperature superconducting (HTS) magnet windings, and the choice of REBCO conductors for cryogen-free carbon-ion gantries. Finally, the paper mentions an important “Prospect for Improvement”, viz: the introduction of MRI image guidance. A well-known property of the particle beam as it passes through tissue is its energy dependent absorption that rises to a pronounced peak (the Bragg peak) at the end of its range. In order to take advantage of this effect the exact targeting of the tumor and positioning of the patient should be guided by imaging visualization using X-ray, CT, and hopefully advanced MRI. Unlike MRI-guided photon therapy the direct interaction of the magnetic field with the charged particle beam presents a huge challenge such that MRI image-guided proton/particle therapy has not yet been available in clinical practice. Modeling studies have been undertaken on the general topic of beam-line/magnetic field interaction using, for example, the software GEANT4 (GEometry And Tracking) a platform for simulating the passage of charged particles through matter using a Monte Carlo method.
Effect of Primary Tumor Location on Second- or Later-Line Treatment With Anti-Epidermal Growth Factor Receptor Antibodies in Patients With Metastatic Colorectal Cancer: A Retrospective Multi-Center Study
Authors: Archwamety Anita , Teeyapun Nattaya , Siripoon Teerada , Poungvarin Naravat , Tanasanvimon Suebpong , Sirachainan Ekaphop , Akewanlop Charuwan , Korphaisarn Krittiya
Published: February 2022

Background

Current guidelines recommend anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR Ab) as first-line treatment only in patients with left-sided RAS wild type (RASwt) metastatic colorectal cancer (mCRC). However, there are no guideline recommendations specific to tumor sidedness in subsequent-line treatment. This study aimed to investigate the effect of primary tumor location on second- or later-line treatment outcomes in patients with KRASwt mCRC.

Methods

Medical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with KRASwt mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test.

Results

Among the 2,102 patients who had KRAS analysis data, 1,130 (54%) patients had KRASwt. Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended RAS analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval [CI]: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p=0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p=0.005).

Conclusions

To date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in KRASwt mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival.
Carbon Ion Beam Boost Irradiation in Malignant Tumors of the Nasal Vestibule and the Anterior Nasal Cavity as an Organ-Preserving Therapy
Authors: Eberle Fabian , Engenhart-Cabillic Rita , Schymalla Markus M. , Dumke Christoph , Schötz Ulrike , Subtil Florentine S.B. , Baumann Kilian-Simon , Stuck Boris A. , Langer Christine , Jensen Alexandra D. , Hauswald Henrik , Lautenschläger Stefan
Published: February 2022

Background

Surgery and radiotherapy are current therapeutic options for malignant tumors involving the nasal vestibule. Depending on the location, organ-preserving resection is not always possible, even for small tumors. Definitive radiotherapy is an alternative as an organ-preserving procedure. Carbon ion beam radiotherapy offers highly conformal dose distributions and more complex biological radiation effects eventually resulting in optimized normal tissue sparing and improved outcome. The aim of the current study was to analyze toxicity, local control (LC), and organ preserving survival (OPS) after irradiation of carcinoma of the nasal vestibule with raster-scanned carbon ion radiotherapy boost (CIRT-B) combined with volumetric intensity modulated arc therapy (VMAT) with photons.

Methods

Between 12/2015 and 05/2021, 21 patients with malignant tumors involving the nasal vestibule were irradiated with CIRT-B combined with VMAT and retrospectively analyzed. Diagnosis was based on histologic findings. A total of 17 patients had squamous cell carcinoma (SCC) and 4 had other histologies. In this series, 10%, 67%, and 24% of patients had Wang stages 1, 2, and 3 tumors, respectively. Three patients had pathologic cervical nodes on MRI. The median CIRT-B dose was 24 Gy(RBE), while the median VMAT dose was 50 Gy. All patients with pathologic cervical nodes received simultaneously integrated boost with photons (SIB) up to a median dose of 62.5 Gy to the pathological lymph nodes. Eight patients received cisplatin chemotherapy. All patients received regular follow-up imaging after irradiation. Kaplan–Meier estimation was used for statistical assessment.

Results

The median follow-up after irradiation was 18.9 months. There were no common toxicity criteria grade 5 or 4 adverse events. A total of 20 patients showed grade 3 adverse events mainly on skin and mucosa. All patients were alive at the end of follow-up. The median OPS after treatment was 56.5 months. The 6- and 24-month OPS were 100% and 83.3%, respectively. All local recurrences occurred within 12 months after radiotherapy. The median progression free survival (PFS) after treatment was 52.4 months. The 6-, 12-, and 24-month PFS rates were 95%, 83.6%, and 74.3%, respectively.

Conclusion

CIRT-B combined with VMAT in malignant tumors of the nasal vestibule is safe and feasible, results in high local control rates, and thus is a good option as organ-preserving therapy. No radiation-associated grade 4 or 5 acute or late AE was documented.
The Effect of Lymph Node Harvest on Prognosis in Locally Advanced Middle-Low Rectal Cancer After Neoadjuvant Chemoradiotherapy
Authors: Lin Zhuangbin , Li Xiaobo , Song Jianyuan , Zheng Rong , Chen Cheng , Li Anchuan , Xu Benhua
Published: February 2022

Objective

The purpose of this study was to investigate the relationship between lymph node harvest and the prognosis in locally advanced rectal cancer (LARC) patients after neoadjuvant chemoradiotherapy (nCRT).

Methods

Patients who were diagnosed with clinical LARC and treated with nCRT and radical surgery between June 2008 and July 2017 were included in this study. The relationship between lymph node retrieval and prognosis was analyzed. Other lymph node-related indicators were explored.

Results

A total of 837 patients with a median follow-up of 61 (7-139) months were included in the study. The five-year DFS and OS rates of all patients were 74.9% and 82.3%, respectively. Multivariate survival analysis suggested that dissection of ≥ 12 lymph nodes did not improve OS or DFS. 7 was selected as the best cutoff value for the total number of lymph nodes retrieved by Cox multivariate analysis (χ2 = 10.072, HR: 0.503, P=0.002). Dissection of ≥ 5 positive lymph nodes (PLNs) was an independent prognostic factor for poorer DFS (HR: 2.104, P=0.004) and OS (HR: 3.471, p<0.001). A positive lymph node ratio (LNR) of more than 0.29 was also an independent prognostic factor for poorer DFS (HR: 1.951, P=0.002) and OS (HR: 2.434, p<0.001).

Conclusion

The recommends that at least 7 harvested lymph nodes may be more appropriate for LARC patients with nCRT. PLN and LNR may be prognostic factors for LARC patients with ypN+ after nCRT.
Characteristics and Outcomes of Chinese Children With Advanced Stage Anaplastic Large Cell Lymphoma: A Single-Center Experience
Authors: Zhang Yu-Tong , Wang Li-Zhe , Chang Jian
Published: February 2022

Purpose

To evaluate the clinical characteristics and treatment outcomes of Chinese children with advanced stage anaplastic large cell lymphoma (ALCL) who were treated with the low-intensity APO regimen.

Methods

Clinical data from children newly diagnosed with advanced stage ALCL and treated with the APO regimen were reviewed.

Results

Altogether 22 eligible patients with advanced stage ALCL were recruited in this study. 18 (81%) patients achieved complete response (CR) after the initial induction, and 4 experienced relapse. Among patients with relapsed or refractory ALCL, CR was achieved in 3 (50%) who received the BFM95 R3/R4 regimen. Besides, 2 patients received the targeted therapy with crizotinib and were still alive. The 5-year OS and EFS rates were 82 ± 8.7% and 68.2 ± 9.4%%, respectively. According to our results, the elevated LDH level and bone marrow involvement were identified as the poor prognostic factors for EFS (p=0.035 and 0.048, respectively). During APO treatment, only 23% patients experienced grade 3-4 hematologic toxicity.

Conclusions

In this study, bone marrow involvement and elevated serum LDH levels were identified as the poor prognostic factors for EFS. In resource-limited regions, patients with advanced stage ALCL can also achieve comparable outcomes to those in high-income regions, and the BFM95 R3/R4 regimen can take the role of salvage treatment for patients with relapsed or refractory disease. Nonetheless, new therapeutic strategy is still needed.
Biological Treatments and Target Therapies for Pediatric Respiratory Medicine: Not Only Asthma
Authors: Ghirardo Sergio , Mazzolai Michele , Di Marco Antonio , Petreschi Francesca , Ullmann Nicola , Ciofi degli Atti Marta Lucia , Cutrera Renato
Published: February 2022

We present a description of pediatric pneumology biological medications and other target therapies. The article aims at introducing the importance of a molecular approach to improve treatments. The first item treated was T2-High asthma and its current biological treatment and prescribing indications to propose a flow-chart to guide the clinical choice. Molecular rationales of such treatments are used to introduce a more general description of the biological and molecular approach to target therapies application. We introduce a general interpretation approach to neutrophilic asthma using the molecular plausibility one in order to propose possible future treatments mainly targeting interleukin-1 (IL-1), IL-17, IL-12, and IL-23. Indeed, cytokines can be excellent targets for several biological treatments. Downregulation of specific cytokines can be crucial in treating autoinflammatory and rheumatological diseases with a pulmonary involvement. Such conditions, although rare, should be early recognized as they can involve significant improvement with a properly targeted therapy. We face these conditions in a cherry-picking fashion picturing SAVI (STING-associated vasculopathy with onset in infancy), CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature), and COPA (coat proteins alpha syndrome) syndrome pulmonary involvement. Such examples are functional to introduce molecular-based approach for patients with rare conditions. Molecular plausibility can be highly valuable in treating patients with not-approved but possibly highly effective therapies. Due to the rarity of these conditions, we stress the concept of basket trials using the example of cytokinin-directed immunosuppressive treatment. Lastly, we provide an example of augmentative therapy using the alpha1 antitrypsin deficiency as a model. In summary, the article presents a collection of the most recent achievements and some possible future developments of target therapies for pediatric pulmonary conditions.
Progress in the Mechanism of Autophagy and Traditional Chinese Medicine Herb Involved in Dementia
Authors: Tao Pengyu , Ji Jing , Gu Simeng , Wang Qian , Xu Yuzhen
Published: February 2022

Dementias is a kind of neurodegenerative disease, which occurs among the aging population. Current therapeutic outcome for dementia is limited. The medical use of herbal plant has a rich history in traditional Chinese medicine practice for thousands of years. Herbal medicine (HM) may provide a positive effect for prevention and treatment in dementia. As an alternative treatment to dementia, there has been a growing interest in HM extracts in scientific community as a result of its promising study results, mainly in animal experiment. At the molecular level, HM extracts trigger autophagy and reduce generation of reactive oxygen species (ROS) while inhibiting inflammation and reduce neurotoxicity. Experiments both in vivo and in vitro have identified certain potential of HM extracts and natural products as an important regulator factor in mediating autophagy, which might contribute to the improvement of dementia. This brief review not only summarizes the mechanism of autophagy in dementia but also offers a general understanding of the therapeutic mechanism of HM extracts in treating dementia and evaluates the potential clinical practice of HM in general.
Comparative Efficacy of Pharmacological Therapies for Low Back Pain: A Bayesian Network Analysis
Authors: Jiang Jiuzhou , Pan Hao , Chen Haomai , Song Liyang , Wang Yiyun , Qian Bao , Chen Pengfei , Fan Shunwu , Lin Xianfeng
Published: February 2022

Low back pain (LBP) is a common problem, but the efficacy of pharmacological therapies remains controversial. Therefore, we aimed to comprehensively evaluate and quantitatively rank various pharmacological therapies for patients with low back pain. Two meta-analyses were performed: an initial pair-wise meta-analysis, followed by network meta-analysis using a random-effects Bayesian model. We included randomized controlled trials comparing placebos, non-steroidal anti-inflammatory drugs, opioids, skeletal muscular relaxants, pregabalin (or gabapentin), and some drug combinations. The primary and secondary outcomes were pain intensity and physical function. Eighty-eight eligible trials with 21,377 patients were included. Here, we show that only skeletal muscle relaxants significantly decreased the pain intensity of acute (including subacute) low back pain. Several kinds of drugs significantly decreased the pain of chronic low back pain, but only opioids and cyclo-oxygenase 2-selective non-steroidal anti-inflammatory drugs effectively reduced pain and improved function. Pregabalin (or gabapentin) seemed to be an effective treatment to relieve pain, but it should be used with caution for low back pain.
Subject-Specific Pressure Normalization of Local Pulse Wave Velocity: Separating Intrinsic From Acute Load-Dependent Stiffening in Hypertensive Patients
Authors: Giudici Alessandro , Palombo Carlo , Kozakova Michaela , Morizzo Carmela , Cruickshank J. Kennedy , Khir Ashraf W.
Published: February 2022

Pulse wave velocity (PWV) is a powerful predictor of cardiovascular events. However, its intrinsic blood pressure (BP)-dependency complicates distinguishing between acute and chronic effects of increased BP on arterial stiffness. Based on the assumption that arteries exhibit a nearly exponential pressure-area (P-A) relationship, this study proposes a method to assess intersubject differences in local PWV independently from BP. The method was then used to analyze differences in local carotid PWV (cPWV) between hypertensive and healthy normotensive people before and after BP-normalization. Pressure (P) and diameter (D) waveforms were simultaneously acquired via tonometer at the left and ultrasound scanning at right common carotid artery (CCA), respectively, in 22 patients with Grade 1 or 2 hypertension and 22 age- and sex-matched controls. cPWV was determined using the D2P-loop method. Then, the exponential modeling of the P-area (A = πD2/4) relationships allowed defining a mathematical formulation to compute subject-specific changes in cPWV associated with BP changes, thus enabling the normalization of cPWV against intersubject differences in BP at the time of measurement. Carotid systolic BP (SBP) and diastolic BP (DBP) were, on average, 17.7 (p < 0.001) and 8.9 mmHg (p < 0.01) higher in hypertensives than controls, respectively. cPWV was 5.56 ± 0.86 m/s in controls and 6.24 ± 1.22 m/s in hypertensives. BP alone accounted for 68% of the cPWV difference between the two groups: 5.80 ± 0.84 vs. 6.03 ± 1.07 m/s after BP-normalization (p = 0.47). The mechanistic normalization of cPWV was in agreement with that estimated by analysis of covariance (ANCOVA). In conclusion, the proposed method, which could be easily implemented in the clinical setting, allows to assess the intersubject differences in PWV independently of BP. Our results suggested that mild hypertension in middle-aged subjects without target organ damage does not significantly alter the stiffness of the CCA wall independently of acute differences in BP. The results warrant further clinical investigations to establish the potential clinical utility of the method.