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1.
BMC Cancer ; 24(1): 464, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38616289

ABSTRACT

PURPOSE: In this study, we retrospectively investigated the prognostic role of pre-treatment neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in esophageal squamous cell carcinoma patients (ESCC) treated with concurrent chemo-radiotherapy (CCRT). METHODS: We retrospectively analyzed the records of 338 patients with pathologically diagnosed esophageal squamous cell carcinoma that underwent concurrent chemo-radiotherapy from January 2013 to December 2017. Univariate and multivariate analyses were used to identify prognostic factors for progression free survival (PFS) and overall survival (OS). RESULTS: The result showed that the thresholds for NLR and PLR were 2.47 and 136.0 by receiver operating characteristic curve. High NLR and PLR were both associated with tumor length (P < 0.05). High NLR and PLR were significantly associated with poor PFS and OS. Multivariate analyses identified NLR, PLR and TNM stage were independent risk factors for PFS and OS. CONCLUSIONS: We show that the pre-treatment NLR and PLR may serve as prognostic indicators for esophageal squamous cell carcinoma treated with concurrent chemo-radiotherapy.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Prognosis , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Neoplasms/therapy , Neutrophils , Retrospective Studies , Chemoradiotherapy , Lymphocytes
2.
J Cancer Res Ther ; 20(2): 540-546, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38687923

ABSTRACT

PURPOSE: To retrospectively study the therapeutic effect and safety performance of the combination strategies of the computed tomography (CT)-guided microwave ablation (MWA) and percutaneous vertebroplasty (PVP) as a treatment for painful non-small cell lung cancer (NSCLC) with spinal metastases. MATERIALS AND METHODS: A retrospective review included 71 patients with 109 vertebral metastases who underwent microwave ablation combined with percutaneous vertebroplasty by the image-guided and real-time temperature monitoring. Treatment efficacy was determined by comparing visual analog scale (VAS) scores, daily morphine equivalent opioid consumption, and Oswestry Disability Index (ODI) scores before treatment and during the follow-up period. RESULTS: Technical success was achieved in all patients. The mean pre-procedure VAS score and morphine doses were 6.6 ± 1.8 (4-10) and 137.2 ± 38.7 (40-200) mg, respectively. The mean VAS scores and daily morphine doses at 24 h and 1, 4, 12, and 24 weeks postoperatively were 3.3 ± 1.9 and 73.5 ± 39.4 mg; 2.2 ± 1.5 and 40.2 ± 29.8 mg; 1.7 ± 1.2 and 31.3 ± 23.6 mg; 1.4 ± 1.1 and 27.3 ± 21.4 mg; and 1.3 ± 1.1 and 24.8 ± 21.0 mg, respectively (all P < 0.001). ODI scores significantly decreased (P < 0.05). Minor cement leakage occurred in 51 cases (46.8%), with one patient having a grade 3 neural injury. No local tumor progression was observed by follow-up imaging. CONCLUSIONS: MWA combined with PVP can significantly relieve pain and improve patients' quality of life, which implied this is an effective treatment option for painful NSCLC with spinal metastases. Additionally, its efficacy should be further verified through the mid- and long-term studies.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Microwaves , Spinal Neoplasms , Vertebroplasty , Humans , Male , Female , Vertebroplasty/methods , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/secondary , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Middle Aged , Microwaves/therapeutic use , Spinal Neoplasms/secondary , Spinal Neoplasms/therapy , Spinal Neoplasms/complications , Aged , Retrospective Studies , Treatment Outcome , Combined Modality Therapy/methods , Pain Measurement , Tomography, X-Ray Computed , Adult , Cancer Pain/etiology , Cancer Pain/therapy , Cancer Pain/diagnosis , Aged, 80 and over , Pain Management/methods , Follow-Up Studies
3.
BMC Neurol ; 23(1): 219, 2023 Jun 08.
Article in English | MEDLINE | ID: mdl-37291501

ABSTRACT

OBJECTIVE: To evaluate the safety and efficacy of computed tomography (CT)-guided microwave ablation combined with vertebral augmentation under real-time temperature monitoring in the treatment of painful osteogenic spinal metastases. METHODS: This retrospective study included 38 patients with 63 osteogenic metastatic spinal lesions treated using CT-guided microwave ablation and vertebral augmentation under real-time temperature monitoring. Visual analog scale scores, daily morphine consumption, and Oswestry Disability Index scores were used to evaluate efficacy of the treatment. RESULTS: Microwave ablation combined with vertebral augmentation reduced the mean visual analog scale scores from 6.40 ± 1.90 preoperatively to 3.32 ± 0.96 at 24 h, 2.24 ± 0.91 at 1 week, 1.92 ± 1.32 at 4 weeks, 1.79 ± 1.45 at 12 weeks, and 1.39 ± 1.12 at 24 weeks postoperatively (all p < 0.001). The mean preoperative daily morphine consumption was 108.95 ± 56.41 mg, which decreased to 50.13 ± 25.46 mg at 24 h, 31.18 ± 18.58 mg at 1 week, 22.50 ± 16.63 mg at 4 weeks, 21.71 ± 17.68 mg at 12 weeks, and 17.27 ± 16.82 mg at 24 weeks postoperatively (all p < 0.001). During the follow-up period, the Oswestry Disability Index scores significantly reduced (p < 0.001). Bone cement leakage occurred in 25 vertebral bodies, with an incidence of 39.7% (25/63). CONCLUSIONS: The results indicate that microwave ablation combined with vertebral augmentation under real-time temperature monitoring is a feasible, effective, and safe treatment for painful osteoblast spinal metastases.


Subject(s)
Spinal Fractures , Spinal Neoplasms , Humans , Spinal Neoplasms/surgery , Spinal Neoplasms/secondary , Microwaves/therapeutic use , Retrospective Studies , Temperature , Treatment Outcome , Pain Measurement , Pain , Morphine/therapeutic use
4.
Metab Eng ; 79: 1-13, 2023 09.
Article in English | MEDLINE | ID: mdl-37364774

ABSTRACT

Many studies have demonstrated that the gut microbiota is associated with human health and disease. Manipulation of the gut microbiota, e.g. supplementation of probiotics, has been suggested to be feasible, but subject to limited therapeutic efficacy. To develop efficient microbiota-targeted diagnostic and therapeutic strategies, metabolic engineering has been applied to construct genetically modified probiotics and synthetic microbial consortia. This review mainly discusses commonly adopted strategies for metabolic engineering in the human gut microbiome, including the use of in silico, in vitro, or in vivo approaches for iterative design and construction of engineered probiotics or microbial consortia. Especially, we highlight how genome-scale metabolic models can be applied to advance our understanding of the gut microbiota. Also, we review the recent applications of metabolic engineering in gut microbiome studies as well as discuss important challenges and opportunities.


Subject(s)
Gastrointestinal Microbiome , Probiotics , Humans , Gastrointestinal Microbiome/genetics , Metabolic Engineering , Probiotics/therapeutic use , Microbial Consortia
5.
Front Oncol ; 13: 1084904, 2023.
Article in English | MEDLINE | ID: mdl-37188195

ABSTRACT

Purpose: To evaluate the efficacy safety of computed tomography (CT)-guided 125I seed implantation by coplanar template for vertebral metastases after failure of external beam radiation therapy (EBRT). Material and methods: Retrospective analysis of the clinical outcomes of 58 patients with vertebral metastases after failure of EBRT, who underwent 125I seed implantation as a salvage treatment with a CT-guided coplanar template-assisted technique from January 2015 to January 2017. Results: The mean post-operative NRS score decreased significantly at T4w (3.5 ± 0.9, p<0.01), T8w (2.1 ± 0.9, p<0.01), T12w (1.5 ± 0.7, p< 0.01) and T6m (1.2 ± 0.6, p< 0.01) respectively. The local control rates after 3, 6, 9 and 12 months were 100% (58/58), 93.1% (54/58), 87.9% (51/58), and 81% (47/58), respectively. The median overall survival time was 18.52months (95% CI, 16.24-20.8), and 1- and 2-year survival rates were 81% (47/58) and 34.5% (20/58), respectively. By performing a paired t-test analysis, there was no significant difference in D90, V90, D100, V100, V150, V200, GTV volume, CI, EI and HI between preoperative and postoperative (p>0.05). Conclusions: 125I seed implantation can be used as a salvage treatment for patients with vertebral metastases after failure of EBRT.

6.
Technol Cancer Res Treat ; 22: 15330338231168458, 2023.
Article in English | MEDLINE | ID: mdl-37038613

ABSTRACT

Background: To compare the safety and efficacy of 2 different computed tomography-guided puncture techniques for simultaneous needle biopsy and microwave ablation of suspected malignant pulmonary nodules. Methods: This retrospective comparative before-and-after study analyzed the data of 81 patients (each with a suspected malignant pulmonary nodule) who underwent computed tomography-guided needle biopsy with simultaneous microwave ablation between September 2016 and September 2021. In group A, 41 patients (41 pulmonary nodules) underwent microwave ablation immediately through the biopsy channel, whereas in group B, 40 patients (40 pulmonary nodules) underwent computed tomography-guided percutaneous needle biopsy and microwave ablation through separate needle channels. Clinical data, technical success rates, complications, and short-term efficacy were compared between the groups to evaluate the advantages and disadvantages of both techniques. Results: Of the 81 patients, 78 successfully underwent needle biopsy and microwave ablation, with a technical success rate of 96.3%. The incidence of pneumothorax was 56.1% (23 out of 41) and 30% (12 out of 40) in groups A and B, respectively, while that of chest pain was 34.1% (14 out of 41) and 40% (16 out of 40) in groups A and B, respectively. The differences were statistically insignificant (p = .127 and p = .759). However, the incidence of hemoptysis was 39.0% (16 out of 41) and 17.5% (7 out of 40), respectively, which was statistically significant (P = .015). Air embolism, bronchopleural fistula, and needle implantation metastasis were not observed in both groups. At a 6-month follow-up, there were no other complications in both groups, and complete ablation was observed in all cases. Conclusion: Computed tomography-guided biopsy combined with microwave ablation is safe and effective for the treatment of suspected malignant pulmonary nodules, and clinicians can use both techniques.


Subject(s)
Lung Neoplasms , Multiple Pulmonary Nodules , Pneumothorax , Humans , Retrospective Studies , Microwaves/therapeutic use , Biopsy, Needle/methods , Pneumothorax/etiology , Pneumothorax/therapy , Multiple Pulmonary Nodules/surgery , Lung Neoplasms/diagnosis , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery
7.
Metab Eng ; 75: 119-130, 2023 01.
Article in English | MEDLINE | ID: mdl-36503050

ABSTRACT

The hybrid cybernetic model (HCM) approach is a dynamic modeling framework that integrates enzyme synthesis and activity regulation. It has been widely applied in bioreaction engineering, particularly in the simulation of microbial growth in different mixtures of carbon sources. In a HCM, the metabolic network is decomposed into elementary flux modes (EFMs), whereby the network can be reduced into a few pathways by yield analysis. However, applying the HCM approach on conventional genome-scale metabolic models (GEMs) is still a challenge due to the high computational demands. Here, we present a HCM strategy that introduced an optimized yield analysis algorithm (opt-yield-FBA) to simulate metabolic dynamics at the genome-scale without the need for EFMs calculation. The opt-yield-FBA is a flux-balance analysis (FBA) based method that can calculate optimal yield solutions and yield space for GEM. With the opt-yield-FBA algorithm, the HCM strategy can be applied to get the yield spaces and avoid the computational burden of EFMs, and it can therefore be applied for developing dynamic models for genome-scale metabolic networks. Here, we illustrate the strategy by applying the concept to simulate the dynamics of microbial communities.


Subject(s)
Genome , Metabolic Networks and Pathways , Metabolic Networks and Pathways/genetics , Algorithms , Computer Simulation , Models, Biological , Metabolic Flux Analysis
8.
BMC Musculoskelet Disord ; 23(1): 1025, 2022 Nov 29.
Article in English | MEDLINE | ID: mdl-36443787

ABSTRACT

BACKGROUND: The spine is the most frequently affected part of the skeletal system to metastatic tumors. External radiotherapy is considered the first-line standard of care for these patients with spine metastases. Recurrent spinal metastases after radiotherapy cannot be treated with further radiotherapy within a short period of time, making treatment difficult. We aimed to evaluate the effectiveness and safety of MWA combined with cementoplasty in the treatment of spinal metastases after radiotherapy under real-time temperature monitoring. METHODS: In this retrospective study, 82 patients with 115 spinal metastatic lesions were treated with MWA and cementoplasty under real-time temperature monitoring. Changes in visual analog scale (VAS) scores, daily morphine consumption, and Oswestry Disability Index (ODI) scores were noted. A paired Student's t-test was used to assess these parameters. Complications during the procedure were graded using the CTCAE version 5.0. RESULTS: Technical success was attained in all patients. The mean VAS score was 6.3 ± 2.0 (range, 4-10) before operation, and remarkable decline was noted in one month (1.7 ± 1.0 [P < .001]), three months (1.4 ± 0.8 [P < .001]), and six months (1.3 ± 0.8 [P < .001]) after the operation. Significant reductions in daily morphine consumption and ODI scores were also observed (P < .05). Cement leakage was found in 27.8% (32/115) of lesions, with no obvious associated symptoms. CONCLUSION: MWA combined with cementoplasty under real-time temperature monitoring is an effective and safe method for recurrent spinal metastases after radiotherapy.


Subject(s)
Cementoplasty , Spinal Neoplasms , Humans , Microwaves/therapeutic use , Retrospective Studies , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/radiotherapy , Temperature , Morphine Derivatives
9.
Microb Cell Fact ; 21(1): 241, 2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36419034

ABSTRACT

Recent studies have demonstrated that gut microbiota plays critical roles in various human diseases. High-throughput technology has been widely applied to characterize the microbial ecosystems, which led to an explosion of different types of molecular profiling data, such as metagenomics, metatranscriptomics and metabolomics. For analysis of such data, machine learning algorithms have shown to be useful for identifying key molecular signatures, discovering potential patient stratifications, and particularly for generating models that can accurately predict phenotypes. In this review, we first discuss how dysbiosis of the intestinal microbiota is linked to human disease development and how potential modulation strategies of the gut microbial ecosystem can be used for disease treatment. In addition, we introduce categories and workflows of different machine learning approaches, and how they can be used to perform integrative analysis of multi-omics data. Finally, we review advances of machine learning in gut microbiome applications and discuss related challenges. Based on this we conclude that machine learning is very well suited for analysis of gut microbiome and that these approaches can be useful for development of gut microbe-targeted therapies, which ultimately can help in achieving personalized and precision medicine.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Humans , Metagenomics , Dysbiosis , Machine Learning
10.
NPJ Biofilms Microbiomes ; 8(1): 84, 2022 10 19.
Article in English | MEDLINE | ID: mdl-36261538

ABSTRACT

Recent studies have shown that probiotic supplementation has beneficial effects on bone metabolism. In a randomized controlled trial (RCT) we demonstrated that supplementation of Lactobacillus reuteri ATCC PTA 6475 reduced bone loss in older women with low bone mineral density. To investigate the mechanisms underlying the effect of L. reuteri ATCC PTA 6475 on bone metabolism, 20 women with the highest changes (good responders) and the lowest changes (poor responders) in tibia total volumetric BMD after one-year supplementation were selected from our previous RCT. In the current study we characterized the gut microbiome composition and function as well as serum metabolome in good responders and poor responders to the probiotic treatment as a secondary analysis. Although there were no significant differences in the microbial composition at high taxonomic levels, gene richness of the gut microbiota was significantly higher (P < 0.01 by the Wilcoxon rank-sum test) and inflammatory state was improved (P < 0.05 by the Wilcoxon signed-rank test) in the good responders at the end of the 12-month daily supplementation. Moreover, detrimental changes including the enrichment of E. coli (adjusted P < 0.05 by DESeq2) and its biofilm formation (P < 0.05 by GSA) observed in the poor responders were alleviated in the good responders by the treatment. Our results indicate that L. reuteri ATCC PTA 6475 supplementation has the potential to prevent a deterioration of the gut microbiota and inflammatory status in elderly women with low bone mineral density, which might have beneficial effects on bone metabolism.


Subject(s)
Bone Diseases, Metabolic , Gastrointestinal Microbiome , Limosilactobacillus reuteri , Probiotics , Female , Humans , Aged , Limosilactobacillus reuteri/metabolism
11.
Comput Math Methods Med ; 2022: 3473445, 2022.
Article in English | MEDLINE | ID: mdl-36035278

ABSTRACT

Background: Gastric signet ring cell carcinoma (SRCC) has shown a growth growing trend worldwide, but its clinicopathological features and prognostic-related risk factors have not been systematically studied. This systematic review was devoted to this. Method: PubMed, Embase, Cochrane Library, and Web of Science databases were retrieved, and retrospective cohort studies comparing clinicopathological features and related risk factors in SRCC patients were included. Results: In SRCC patient population, males were more than females (male, OR = 1.38, 95% CI: 1.20-1.60); N3 patients were more than N0-2 patients (N0-2, OR = 3.19, 95% CI: 1.98-5.15); M1 patients were more than M0 patients (M0, OR = 3.30, 95% CI: 1.88-5.80); patients with tumor > 5 cm were more than those with tumor (≤5 cm, OR = 7.36, 95% CI: 1.33-40.60). Patients with age < 60 years (age ≥ 60 years, OR = 1.03, 95% CI: 1.01-1.05), lymphatic vessel invasion (no, OR = 1.74, 95% CI: 1.03-2.45), T2 (T1, OR = 1.17, 95% CI: 1.07-1.28) and T4 (T1, OR = 2.55, 95% CI: 2.30-2.81) stages, and N1 (N0, OR = 1.73, 95% CI: 1.08-2.38), N2 (N0, OR = 2.24, 95% CI: 1.12-3.36), and N3 (N0, OR = 3.45, 95% CI: 1.58-5.32) stages had higher hazard ratio (HR). Conclusion: SRCC may occur frequently in male. Age, lymphatic vessel invasion, TN, and M stage may be risk factors for poor prognoses of SRCC patients.


Subject(s)
Carcinoma, Signet Ring Cell , Stomach Neoplasms , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Factors
12.
Technol Cancer Res Treat ; 21: 15330338221103102, 2022.
Article in English | MEDLINE | ID: mdl-35656785

ABSTRACT

Purpose: To analyze the outcome and prognosis of patients with refractory cervical lymph node metastasis of thoracic esophageal squamous cell carcinoma after external irradiation, who underwent interstitial 125I brachytherapy as a salvage treatment with a CT-guided coplanar template-assisted technique. We also want to compare the dosimetry of 3D printed coplanar template-assisted interstitial 125I brachytherapy preoperative and postoperative, and to explore the accuracy of this technology. Material and methods: We retrospectively collected and analyzed the results of 32 patients with refractory cervical lymph node metastasis of thoracic esophageal squamous cell carcinoma after external irradiation, who underwent interstitial 125I brachytherapy as a salvage treatment with a CT-guided coplanar template-assisted technique from January 2012 to December 2017. Results: The actual D90 were 114 to 240 Gy, and the median postoperative dosimetry assessment was 177.5 Gy. The local control rates at 3, 6, 9, and 12 months were 87.5%, 59.38%, 40.63%, and 31.25%, respectively. The median local control time was 7.5 months. The median overall survival time was 10.5 months (95% CI, 8.9-13.4), and the survival rates of 1- and 2-year, respectively, were 43.75% and 9.38%. There were 36 lesions in 32 patients. By performing a paired t-test analysis, there was no significant difference in D90, D100, V100, V150, V200, GTV volume, CI, EI, and HI between preoperative and postoperative (P > .05). Conclusions: Interstitial 125I brachytherapy can be used as a salvage treatment for patients with refractory cervical lymph node metastasis of thoracic esophageal squamous cell carcinoma after external irradiation. With the auxiliary function of 3D printed coplanar template, the main dosimetry parameters verified after the operation can meet the requirements of the preoperative plan with good treatment accuracy.


Subject(s)
Brachytherapy , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Brachytherapy/methods , Esophageal Neoplasms/pathology , Esophageal Neoplasms/radiotherapy , Esophageal Squamous Cell Carcinoma/radiotherapy , Humans , Iodine Radioisotopes , Lymphatic Metastasis , Radiotherapy Dosage , Retrospective Studies , Salvage Therapy , Tomography, X-Ray Computed
13.
Nat Med ; 28(2): 303-314, 2022 02.
Article in English | MEDLINE | ID: mdl-35177860

ABSTRACT

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Microbiota , Humans , Longitudinal Studies , Metabolome , Middle Aged
14.
BMC Biotechnol ; 21(1): 46, 2021 07 30.
Article in English | MEDLINE | ID: mdl-34330235

ABSTRACT

BACKGROUND: Limosilactobacillus reuteri (earlier known as Lactobacillus reuteri) is a well-studied lactic acid bacterium, with some specific strains used as probiotics, that exists in different hosts such as human, pig, goat, mouse and rat, with multiple body sites such as the gastrointestinal tract, breast milk and mouth. Numerous studies have confirmed the beneficial effects of orally administered specific L. reuteri strains, such as preventing bone loss and promoting regulatory immune system development. L. reuteri ATCC PTA 6475 is a widely used strain that has been applied in the market as a probiotic due to its positive effects on the human host. Its health benefits may be due, in part, to the production of beneficial metabolites. Considering the strain-specific effects and genetic diversity of L. reuteri strains, we were interested to study the metabolic versatility of these strains. RESULTS: In this study, we aimed to systematically investigate the metabolic features and diversities of L. reuteri strains by using genome-scale metabolic models (GEMs). The GEM of L. reuteri ATCC PTA 6475 was reconstructed with a template-based method and curated manually. The final GEM iHL622 of L. reuteri ATCC PTA 6475 contains 894 reactions and 726 metabolites linked to 622 metabolic genes, which can be used to simulate growth and amino acids utilization. Furthermore, we built GEMs for the other 35 L. reuteri strains from three types of hosts. The comparison of the L. reuteri GEMs identified potential metabolic products linked to the adaptation to the host. CONCLUSIONS: The GEM of L. reuteri ATCC PTA 6475 can be used to simulate metabolic capabilities and growth. The core and pan model of 35 L. reuteri strains shows metabolic capacity differences both between and within the host groups. The GEMs provide a reliable basis to investigate the metabolism of L. reuteri in detail and their potential benefits on the host.


Subject(s)
Genome, Bacterial , Limosilactobacillus reuteri/genetics , Limosilactobacillus reuteri/metabolism , Animals , Goats , Host Specificity , Humans , Limosilactobacillus reuteri/growth & development , Mice , Rats , Swine
15.
JBMR Plus ; 5(4): e10478, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33869994

ABSTRACT

Osteoporosis and its associated fractures are highly prevalent in older women. Recent studies have shown that gut microbiota play important roles in regulating bone metabolism. A previous randomized controlled trial (RCT) found that supplementation with Lactobacillus reuteri ATCC PTA 6475 (L.reuteri) led to substantially reduced bone loss in older women with low BMD. However, the total metabolic effects of L. reuteri supplementation on older women are still not clear. In this study, a post hoc analysis (not predefined) of serum metabolomic profiles of older women from the previous RCT was performed to investigate the metabolic dynamics over 1 year and to evaluate the effects of L. reuteri supplementation on human metabolism. Distinct segregation of the L. reuteri and placebo groups in response to the treatment was revealed by partial least squares-discriminant analysis. Although no individual metabolite was differentially and significantly associated with treatment after correction for multiple testing, 97 metabolites responded differentially at any one time point between L. reuteri and placebo groups (variable importance in projection score >1 and p value <0.05). These metabolites were involved in multiple processes, including amino acid, peptide, and lipid metabolism. Butyrylcarnitine was particularly increased at all investigated time points in the L. reuteri group compared with placebo, indicating that the effects of L. reuteri on bone loss are mediated through butyrate signaling. Furthermore, the metabolomic profiles in a case (low BMD) and control population (high BMD) of elderly women were analyzed to confirm the associations between BMD and the identified metabolites regulated by L. reuteri supplementation. The amino acids, especially branched-chain amino acids, showed association with L. reuteri treatment and with low BMD in older women, and may serve as potential therapeutic targets. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

16.
Clin Gastroenterol Hepatol ; 19(7): 1366-1376.e2, 2021 07.
Article in English | MEDLINE | ID: mdl-32668338

ABSTRACT

BACKGROUND & AIMS: Patients with Crohn's disease (CD) or ulcerative colitis (UC) often receive combination therapy with an immunomodulator and tumor necrosis factor antagonists, especially infliximab. However, the benefits of combination therapy with vedolizumab and ustekinumab are unclear. METHODS: We performed a retrospective study of patients with CD or UC initiating vedolizumab or ustekinumab therapy at Massachusetts General Hospital (USA), Alberta Health Sciences (Canada), or Nancy University Hospital (France) with at least 1 year of follow up. The primary outcome was clinical remission or response at week 14, based on the Harvey Bradshaw index for CD or simple clinical colitis index or partial Mayo score for UC. We separately examined week 30 and week 54 clinical outcomes, endoscopic response, and durability of therapy using multivariable regression models and adjusting for relevant confounders. RESULTS: Our study included 549 patients (263 with UC, 286 with CD) receiving maintenance therapy with vedolizumab and 363 patients (4 with UC, 359 with CD) receiving maintenance therapy with ustekinumab with 1 year of follow up. The mean disease duration was 13-15 years. One-hundred thirty-one patients receiving vedolizumab (23.9%; 78 receiving thiopurine, 53 receiving methotrexate) and 120 patients receiving ustekinumab (33.1%, 57 receiving thiopurine, 63 receiving methotrexate) were receiving combination therapy. For vedolizumab, there was no difference in clinical response or remission with combination therapy vs monotherapy at week 14 (68.2% vs 74.1%; P = .22), week 30 (74.3% vs 75.6%; P = .78) or week 54 (78.3% vs 72.9%, P = .33). For ustekinumab, there was no difference in clinical response or remission with combination therapy vs monotherapy at week 14 (54.6% vs 65.8%; P = .08), week 30 (71.6% vs 77.4%; P = .33) or week 54 (62.1% vs 67.0%; P = .52). There were similar proportions of patients remaining on treatment or with endoscopic response at 1 year among patients receiving combination or monotherapy with vedolizumab or ustekinumab. CONCLUSIONS: In patients with CD or UC initiating ustekinumab or vedolizumab therapy, combination therapy with immunomodulators did not increase rates of clinical remission or response, endoscopic remission, or persistence of therapy at 1 year.


Subject(s)
Colitis, Ulcerative , Inflammatory Bowel Diseases , Alberta , Antibodies, Monoclonal, Humanized , Colitis, Ulcerative/drug therapy , Gastrointestinal Agents/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Remission Induction , Retrospective Studies , Treatment Outcome , Ustekinumab/therapeutic use
17.
BMC Cancer ; 20(1): 736, 2020 08 07.
Article in English | MEDLINE | ID: mdl-32767991

ABSTRACT

An amendment to this paper has been published and can be accessed via the original article.

18.
BMC Cancer ; 20(1): 591, 2020 Jun 24.
Article in English | MEDLINE | ID: mdl-32580723

ABSTRACT

BACKGROUND: The prognosis of patients with progressive or recurrent high-grade gliomas (HGGs) after surgery remains poor. Iodine-125 brachytherapy is emerging as a salvage method for the treatment of gliomas. This study aimed to investigate whether permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection. METHODS: Between March 2004 and August 2016, 58 patients with progressive or recurrent HGG after gross total resection were included in this study. Twenty-nine patients underwent radiotherapy and/or chemotherapy and then permanent iodine-125 brachytherapy (SRCI group). Twenty-nine patients underwent permanent iodine-125 brachytherapy alone (SI group). Follow-up was carried out at 1, 3, and 6 months and then at 1, 2, 3, and 5 years after iodine-125 implantation. The median overall survival (OS) and progression-free survival (PFS), procedure-related complications and clinical outcomes were evaluated. RESULTS: No procedure-related fatal events happened. The temporary morbidity rate was 11.9%. The median OS and PFS for patients in the SI group were 22 and 8 months compared with 21 and 7 months in the SRCI group. No significant differences were found. Age and Karnofsky Performance Status (KPS) were independent prognostic factors for OS. Age, KPS and histology were independent prognostic factors for PFS. CONCLUSIONS: Permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection.


Subject(s)
Brachytherapy/methods , Brain Neoplasms/therapy , Glioma/therapy , Neoplasm Recurrence, Local/radiotherapy , Salvage Therapy/methods , Adolescent , Adult , Age Factors , Aged , Brachytherapy/adverse effects , Brain/pathology , Brain/radiation effects , Brain/surgery , Brain Neoplasms/diagnosis , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Female , Follow-Up Studies , Glioma/diagnosis , Glioma/mortality , Glioma/pathology , Humans , Iodine Radioisotopes/administration & dosage , Iodine Radioisotopes/adverse effects , Karnofsky Performance Status , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Prognosis , Progression-Free Survival , Radiotherapy, Adjuvant/methods , Retrospective Studies , Risk Factors , Salvage Therapy/adverse effects , Young Adult
19.
Eur Radiol ; 30(5): 2692-2702, 2020 May.
Article in English | MEDLINE | ID: mdl-32020400

ABSTRACT

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.


Subject(s)
Adenocarcinoma of Lung/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Microwaves/therapeutic use , Neoplasm Recurrence, Local/therapy , Radiofrequency Ablation/methods , Adenocarcinoma of Lung/pathology , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Combined Modality Therapy , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Docetaxel/administration & dosage , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Organoplatinum Compounds/administration & dosage , Paclitaxel/administration & dosage , Pemetrexed/administration & dosage , Progression-Free Survival , Prospective Studies , Treatment Outcome , Vinorelbine/administration & dosage , Gemcitabine
20.
J Cancer Res Ther ; 16(7): 1714-1717, 2020.
Article in English | MEDLINE | ID: mdl-33565522

ABSTRACT

Humerus is the long bone second-most commonly affected by metastases. An impending pathologic humeral fracture requires rigid surgical stabilization to prevent it from fully fracturing. In the present study, we report a case of a 71-year-old male patient with a visual analog score of 10 (indicating extreme pain) and an impending pathologic fracture that allowed for combined treatment with percutaneous microwave ablation and simultaneous injection of bone cement during Kirschner wire insertion. The procedure was performed successfully with no complications. The patient reported pain relief and improved quality of life and functional status 1 day, 7 days, 1 month, and 2 months after his procedure.


Subject(s)
Adenocarcinoma/complications , Bone Neoplasms/complications , Cancer Pain/therapy , Fractures, Spontaneous/therapy , Humerus/pathology , Radiofrequency Ablation/methods , Adenocarcinoma/secondary , Adenocarcinoma/therapy , Aged , Bone Cements , Bone Neoplasms/secondary , Bone Neoplasms/therapy , Bone Wires , Cancer Pain/diagnosis , Cancer Pain/etiology , Cancer Pain/psychology , Fracture Fixation, Internal/instrumentation , Fracture Fixation, Internal/methods , Fractures, Spontaneous/etiology , Fractures, Spontaneous/pathology , Humans , Humerus/surgery , Male , Microwaves/therapeutic use , Pain Measurement , Quality of Life , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Treatment Outcome
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