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1.
Obes Surg ; 34(7): 2317-2328, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38851646

RESUMO

INTRODUCTION: This study aimed to evaluate the impact of achieving < 37.7% excess body-weight loss (EBWL) within 3 months of postlaparoscopic sleeve gastrectomy (LSG) on clinical outcomes and its correlation with adipocyte function. METHODS: Patients (n = 176) who underwent LSG between January 2019 and January 2023 were included. Weight loss and status of health markers were monitored postoperatively. The cohort was stratified based on EBWL < 37.7% at 3 months or not. Variables including neutrophil-to-lymphocyte ratio (NLR), insulin resistance, and comorbidities were analyzed. Omental visceral and subcutaneous adipose tissue samples were used to analyze the differences in adipocyte function by western blot. RESULTS: Patients with EBWL < 37.7% at 3 months post-LSG (suboptimal group) comprised less likelihood of achieving ≥ 50% EBWL than those who achieved ≥ 37.7% EBWL (optimal group) at 6 months (42.55% vs. 95.52% in optimal group, p < 0.001), 12 months (85.11% vs. 99.25% in optimal group, p < 0.001) and 24 months (77.14% vs. 94.74% in optimal group, p = 0.009) post-LSG. High BMI (OR = 1.222, 95% CI 1.138-1.312, p < 0.001), NLR ≥ 2.36 (OR = 2.915, 95% CI 1.257-6.670, p = 0.013), and female sex (OR = 3.243, 95% CI 1.306-8.051, p = 0.011) significantly predicted EBWL < 37.7% at 3 months post-LSG. Patients with NLR ≥ 2.36 had significantly lower adipose triglyceride lipase in omental fat (p = 0.025). CONCLUSION: EBWL < 37.7% at 3 months post-LSG is a strong predictor of subsequent suboptimal weight loss. High BMI, NLR ≥ 2.36, and female sex are risk factors in predicting EBWL < 37.7% at 3 months post-LSG. These findings may offer a reference to apply adjuvant weight loss medications to patients who are predisposed to suboptimal outcomes.


Assuntos
Gastrectomia , Laparoscopia , Linfócitos , Neutrófilos , Obesidade Mórbida , Redução de Peso , Humanos , Feminino , Masculino , Redução de Peso/fisiologia , Adulto , Fatores de Risco , Obesidade Mórbida/cirurgia , Pessoa de Meia-Idade , Adipócitos , Resultado do Tratamento , Estudos Retrospectivos
2.
Obes Surg ; 34(7): 2347-2355, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38771478

RESUMO

INTRODUCTION: Defining recurrent weight gain after metabolic bariatric surgery poses a significant challenge. Our study aimed to standardize recurrent weight gain measurements in patients undergoing laparoscopic sleeve gastrectomy (LSG) and ascertain its association with comorbidity progression. METHODS: We conducted a retrospective data analysis on 122 patients who underwent LSG, tracking their progress over 2-7 years. Data on weight, blood pressure measurements, and laboratory tests were collected, focusing on the postoperative period to identify nadir weight, total weight loss, and recurrent weight gain. RESULTS: Significant weight loss and comorbidity remission were noted, with diabetes, hypertension, and dyslipidemia showing substantial remission rates of 85.71%, 68.24%, and 85.37%, respectively. The median recurrent weight gain was 6.30 kg within 12 months of the nadir. Progression proportion of diabetes, hypertension, and dyslipidemia were 8.20%, 44.26%, and 40.98%, respectively. Hypertension progression was strongly associated with a recurrent weight gain ≥ 10 kg and ≥ 20% of maximum weight loss. Dyslipidemia progression was significantly correlated with recurrent weight gain ≥ 10 kg and ≥ 20% of maximum weight loss. Diabetes progression was significantly correlated with recurrent weight gain ≥ 10% of pre-surgery body weight and ≥ 25% of maximum weight loss. A ≥ 10% weight gain of maximum weight loss did not significantly impact the progression of these conditions. CONCLUSION: Recurrent weight gain ≥ 20% of maximum weight loss can be treated as a specific threshold indicating comorbidity progression post-LSG. Standardizing the measurement of recurrent weight gain can help healthcare providers to implement targeted management strategies to optimize long-term health outcomes.


Assuntos
Comorbidade , Progressão da Doença , Dislipidemias , Gastrectomia , Hipertensão , Laparoscopia , Obesidade Mórbida , Aumento de Peso , Redução de Peso , Humanos , Estudos Retrospectivos , Feminino , Masculino , Adulto , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Dislipidemias/epidemiologia , Gastrectomia/métodos , Pessoa de Meia-Idade , Redução de Peso/fisiologia , Hipertensão/epidemiologia , Recidiva
3.
Surg Endosc ; 38(5): 2433-2443, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38453749

RESUMO

BACKGROUND: Despite a significant 30% ten-year readmission rate for SBO patients, investigations into recurrent risk factors after non-operative management are scarce. The study aims to generate a risk factor scoring system, the 'Small Bowel Obstruction Recurrence Score' (SBORS), predicting 6-month recurrence of small bowel obstruction (SBO) after successful non-surgical management in patients who have history of intra-abdominal surgery. METHODS: We analyzed data from patients aged ≥ 18 with a history of intra-abdominal surgery and diagnosed with SBO (ICD-9 code: 560, 568) and were successful treated non-surgically between 2004 and 2008. Participants were divided into model-derivation (80%) and validation (20%) group. RESULTS: We analyzed 23,901 patients and developed the SBORS based on factors including the length of hospital stay > 4 days, previous operations > once, hemiplegia, extra-abdominal and intra-abdominal malignancy, esophagogastric surgery and intestino-colonic surgery. Scores > 2 indicated higher rates and risks of recurrence within 6 months (12.96% vs. 7.27%, OR 1.898, p < 0.001 in model-derivation group, 12.60% vs. 7.05%, OR 1.901, p < 0.001 in validation group) with a significantly increased risk of mortality and operative events for recurrent episodes. The SBORS model demonstrated good calibration and acceptable discrimination, with an area under curve values of 0.607 and 0.599 for the score generation and validation group, respectively. CONCLUSIONS: We established the effective 'SBORS' to predict 6-month SBO recurrence risk in patients who have history of intra-abdominal surgery and have been successfully managed non-surgically for the initial obstruction event. Those with scores > 2 face higher recurrence rates and operative risks after successful non-surgical management.


Assuntos
Obstrução Intestinal , Intestino Delgado , Recidiva , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Intestino Delgado/cirurgia , Idoso , Medição de Risco , Taiwan/epidemiologia , Fatores de Risco , Adulto , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
4.
Histopathology ; 84(6): 983-1002, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38288642

RESUMO

AIMS: Risk stratification of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), diagnosed using breast biopsy, has great clinical significance. Clinical trials are currently exploring the possibility of active surveillance for low-risk lesions, whereas axillary lymph node staging may be considered during surgical planning for high-risk lesions. We aimed to develop a machine-learning algorithm based on whole-slide images of breast biopsy specimens and clinical information to predict the risk of upstaging to invasive breast cancer after wide excision. METHODS AND RESULTS: Patients diagnosed with ADH/DCIS on breast biopsy were included in this study, comprising 592 (740 slides) and 141 (198 slides) patients in the development and independent testing cohorts, respectively. Histological grading of the lesions was independently evaluated by two pathologists. Clinical information, including biopsy method, lesion size, and Breast Imaging Reporting and Data System (BI-RADS) classification of ultrasound and mammograms, were collected. Deep DCIS consisted of three deep neural networks to evaluate nuclear grade, necrosis, and stromal reactivity. Deep DCIS output comprised five parameters: total patches, lesion extent, Deep Grade, Deep Necrosis, and Deep Stroma. Deep DCIS highly correlated with the pathologists' evaluations of both slide- and patient-level labels. All five parameters of Deep DCIS were significantly associated with upstaging to invasive carcinoma in subsequent wide excisional specimens. Using multivariate logistic regression, Deep DCIS predicted upstaging to invasive carcinoma with an area under the curve (AUC) of 0.81, outperforming pathologists' evaluation (AUC, 0.71 and 0.69). After including clinical and hormone receptor status information, performance further improved (AUC, 0.87). This combined model retained its predictive power in two subgroup analyses: the first subgroup included unequivocal DCIS (excluding cases of ADH and DCIS suspicious for microinvasion) (AUC, 0.83), while the second excluded cases of high-grade DCIS (AUC, 0.81). The model was validated in an independent testing cohort (AUC, 0.81). CONCLUSION: This study demonstrated that deep-learning models can refine histological evaluation of ADH and DCIS on breast biopsies, which may help guide future treatment planning.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Aprendizado Profundo , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/patologia , Mama/patologia , Neoplasias da Mama/patologia , Biópsia , Necrose/patologia , Carcinoma Ductal de Mama/patologia , Estudos Retrospectivos , Hiperplasia/patologia
5.
BMC Cancer ; 24(1): 121, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267903

RESUMO

BACKGROUND: Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are the two most common immune checkpoints targeted in triple-negative breast cancer (BC). Refining patient selection for immunotherapy is non-trivial and finding an appropriate digital pathology framework for spatial analysis of theranostic biomarkers for PD-1/PD-L1 inhibitors remains an unmet clinical need. METHODS: We describe a novel computer-assisted tool for three-dimensional (3D) imaging of PD-L1 expression in immunofluorescence-stained and optically cleared BC specimens (n = 20). The proposed 3D framework appeared to be feasible and showed a high overall agreement with traditional, clinical-grade two-dimensional (2D) staining techniques. Additionally, the results obtained for automated immune cell detection and analysis of PD-L1 expression were satisfactory. RESULTS: The spatial distribution of PD-L1 expression was heterogeneous across various BC tissue layers in the 3D space. Notably, there were six cases (30%) wherein PD-L1 expression levels along different layers crossed the 1% threshold for admitting patients to PD-1/PD-L1 inhibitors. The average PD-L1 expression in 3D space was different from that of traditional immunohistochemistry (IHC) in eight cases (40%). Pending further standardization and optimization, we expect that our technology will become a valuable addition for assessing PD-L1 expression in patients with BC. CONCLUSION: Via a single round of immunofluorescence imaging, our approach may provide a considerable improvement in patient stratification for cancer immunotherapy as compared with standard techniques.


Assuntos
Antígeno B7-H1 , Neoplasias da Mama , Humanos , Feminino , Imageamento Tridimensional , Inibidores de Checkpoint Imunológico , Ligantes , Receptor de Morte Celular Programada 1 , Corantes , Computadores
6.
Am J Cancer Res ; 13(10): 4661-4677, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970352

RESUMO

Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to the limited targeted therapies available at present. Cancer cells preferentially use glycolysis as their primary source of energy, characterized by increased glucose uptake and lactate production. JTC-801, a nociception/orphanin FQ opioid peptide (NOP) receptor antagonist, was reported to suppress the opioid receptor-like1 (ORL1) receptor/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)-κB-mediated carbonic anhydrase 9 (CA9) signaling pathway. Sodium oxamate is an inhibitor of gluconeogenesis and a glycolysis inhibitor, as a competitive lactate dehydrogenase A (LDHA) inhibitor, which also produces tumor suppression due to loss of LDHA activity. However, the roles of opioid analgesic drugs (e.g., JTC-801) and glycolysis inhibitors (e.g., sodium oxamate) in TNBC have not fully been explored. Meanwhile, concurrent treatment with JTC-801 and sodium oxamate may cause synergistic anticancer effects in a TNBC model. In the present study, the combination of JTC-801 and sodium oxamate triggered cell death in the TNBC MDA MB-231 cell line. RNA-sequencing data revealed potential genes in the crosstalk between JTC-801 and sodium oxamate including ALDOC, DDIT4, DHTKD1, EIF6, ENO1, ENO3, FOXK1, FOXK2, HIF1A, MYC, PFKM, PFKP, PPARA, etc. The combination of JTC-801 and sodium oxamate provides a novel potential therapeutic strategy for TNBC patients via downregulating cell cycle- and amino acid metabolism-related pathways such as "Cell cycle-the metaphase checkpoint", "(L)-tryptophan pathways and transport", and "Glutamic acid pathway". Collectively, the present study demonstrated that the synergistic effect of co-treatment with JTC-801 and sodium oxamate significantly suppressed tumor growth and played a crucial role in tumor development, and in turn may serve as potential synergistic drugs for TNBC.

7.
Medicine (Baltimore) ; 102(31): e34423, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37543779

RESUMO

BACKGROUND: A long-acting κreceptor agonist parenteral analgesic may theoretically improve acute pain and reduce incidence of chronic postsurgical pain (CPSP) after laparoscopic cholecystectomy with minimal drug-related side effects of the traditional µreceptor opioids. METHODS: Eighty adult patients undergoing elective laparoscopic cholecystectomy were randomly assigned to receive single intramuscular injection of an extended-release sebacoyl dinalbuphine ester (SDE, Naldebain 150 mg; n = 40) or placebo (n = 40) after anesthesia induction. Standard multimodal analgesia (MMA) was administered for postoperative pain control. The primary endpoint was pain intensity within 7 days after surgery. The secondary endpoints were incidence CPSP at 3 months and adverse reactions up to 7 days after surgery. RESULTS: The highest visual analogue scale (VAS) and area under the curve of VAS 0 to 48 hours after operation were not different between the two groups and a similar proportion of patients requested rescue parenteral analgesics. Average pain intensities were also not different at 72 hours and 7 days after surgery. Incidence of CPSP was 22.5% and 13.1% in patients who received placebo and SDE treatment, respectively (P = .379). Significantly higher incidence of drug-related adverse events, including dizziness, nausea and injection site reactions, were recorded in the SDE group. CONCLUSION: A single dose of extended-release analgesic SDE given intraoperatively did not provide sufficient add-on effect for acute and chronic pain management after laparoscopic cholecystectomies in patients who received standard postoperative MMA. Intramuscular injection of 150 mg SDE in patients with average body mass causes adverse events that could have been overlooked. More clinical studies are warranted to determine the target populations who may benefit from SDE injections for improvement of acute and chronic postsurgical pain management.


Assuntos
Colecistectomia Laparoscópica , Nalbufina , Adulto , Humanos , Colecistectomia Laparoscópica/efeitos adversos , Analgésicos/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Analgésicos Opioides/efeitos adversos , Método Duplo-Cego
8.
Surg Endosc ; 37(9): 6834-6843, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37308764

RESUMO

BACKGROUND: The major treatment for perforated peptic ulcers (PPU) is surgery. It remains unclear which patient may not get benefit from surgery due to comorbidity. This study aimed to generate a scoring system by predicting mortality for patients with PPU who received non-operative management (NOM) and surgical treatment. METHOD: We extracted the admission data of adult (≥ 18 years) patients with PPU disease from the NHIRD database. We randomly divided patients into 80% model derivation and 20% validation cohorts. Multivariate analysis with a logistic regression model was applied to generate the scoring system, PPUMS. We then apply the scoring system to the validation group. RESULT: The PPUMS score ranged from 0 to 8 points, composite with age (< 45: 0 points, 45-65: 1 point, 65-80: 2 points, > 80: 3 points), and five comorbidities (congestive heart failure, severe liver disease, renal disease, history of malignancy, and obesity: 1 point each). The areas under ROC curve were 0.785 and 0.787 in the derivation and validation groups. The in-hospital mortality rates in the derivation group were 0.6% (0 points), 3.4% (1 point), 9.0% (2 points), 19.0% (3 points), 30.2% (4 points), and 45.9% when PPUMS > 4 point. Patients with PPUMS > 4 had a similar in-hospital mortality risk between the surgery group [laparotomy: odds ratio (OR) = 0.729, p = 0.320, laparoscopy: OR = 0.772, p = 0.697] and the non-surgery group. We identified similar results in the validation group. CONCLUSION: PPUMS scoring system effectively predicts in-hospital mortality for perforated peptic ulcer patients. It factors in age and specific comorbidities is highly predictive and well-calibrated with a reliable AUC of 0.785-0.787. Surgery, no matter laparotomy or laparoscope, significantly reduced mortality for scores < = 4. However, patients with a score > 4 did not show this difference, calling for tailored approaches to treatment based on risk assessment. Further prospective validation is suggested.


Assuntos
Laparoscopia , Úlcera Péptica Perfurada , Adulto , Humanos , Resultado do Tratamento , Mortalidade Hospitalar , Medição de Risco , Laparoscopia/métodos , Úlcera Péptica Perfurada/etiologia , Estudos Retrospectivos
9.
J Lipid Atheroscler ; 12(2): 119-131, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37265847

RESUMO

Patients with a history of cardiovascular disease (CVD) who contract coronavirus disease 2019 (COVID-19) tend to have a worse prognosis and more severe cardiovascular side effects. COVID-19 vaccines, which are intended to prevent COVID-19, may also potentially reduce the severity and complications (including cardiovascular sequelae) of COVID-19, especially in patients with a history of CVD. However, there have also been reports of cardiovascular side effects from COVID-19 vaccines of various brands and types. The purpose of this study is to review the benefits and harms of COVID-19 vaccines in relation to CVD. In this thorough review of the most current evidence on the benefits and harms of COVID-19 vaccines, we present information about the characteristics of cardiovascular complications. Most of the evidence focuses on myocarditis or pericarditis, which are most strongly associated with mRNA vaccines and predominantly occur in young males within days of receiving the second dose. Meanwhile, post-vaccination myocardial infarction is more common in older males, and the first dose of adenoviral vector vaccines appears to play a greater role in this complication. This information may guide us in formulating alternative options and implementing targeted surveillance. Gaining more knowledge about the potential benefits and harms of COVID-19 vaccines will improve our ability to make informed decisions and judgments about the balance of these factors.

10.
Am J Cancer Res ; 13(5): 1952-1969, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293150

RESUMO

Tumor progression is dependent on tumor cells and their microenvironment. It is important to identify therapies that inhibit cancer cells and activate immune cells. Arginine modulation plays a dual role in cancer therapy. Arginase inhibition induced an anti-tumor effect via T-cell activation through an increase in arginine in the tumor environment. In contrast, arginine depletion by arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG 20) induced an anti-tumor response in argininosuccinate synthase 1 (ASS1)-deficient tumor cells. ADI-PEG 20 did not cause toxicity to normal immune cells, which can recycle the ADI-degraded product citrulline back to arginine. To target tumor cells and their neighboring immune cells, we hypothesized that the combination of an arginase inhibitor (L-Norvaline) and ADI-PEG 20 may trigger a stronger anticancer response. In this study, we found that L-Norvaline inhibits tumor growth in vivo. Pathway analysis based on RNA-seq data indicated that the differentially expressed genes (DEGs) were significantly enriched in some immune-related pathways. Significantly, L-Norvaline did not inhibit tumor growth in immunodeficient mice. In addition, combination treatment with L-Norvaline and ADI-PEG 20 induced a more robust anti-tumor response against B16F10 melanoma. Furthermore, single-cell RNA-seq data demonstrated that the combination therapy increased tumor-infiltrating CD8+ T cells and CCR7+ dendritic cells. The increase in infiltrated dendritic cells may enhance the anti-tumor response of CD8+ cytotoxic T cells, indicating a potential mechanism for the observed anti-tumor effect of the combination treatment. In addition, populations of immunosuppressive-like immune cells, such as S100a8+ S100a9+ monocytes and Retnla+ Retnlg+ TAMs, in tumors were dramatically decreased. Importantly, mechanistic analysis indicated that the processes of the cell cycle, ribonucleoprotein complex biogenesis, and ribosome biogenesis were upregulated after combination treatment. This study implied the possibility of L-Norvaline as a modulator of the immune response in cancer and provided a new potential therapy combined with ADI-PEG 20.

11.
Obes Surg ; 33(4): 1192-1201, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36787017

RESUMO

PURPOSE: µ-receptor opioids are associated with unwanted gastrointestinal side effects and respiratory depression. A long-acting non-µ-receptor parenteral opioid is not currently available for management of acute and chronic postsurgical pain (CPSP). This double-blind clinical trial tested an extended-release κ-receptor agonist, sebacoyl dinalbuphine ester (SDE, Naldebain®) for management of surgical pain after laparoscopic bariatric surgery. MATERIALS AND METHODS: Patients were randomly assigned to receive a single intramuscular injection of SDE (150 mg, n = 30) or vehicle solution (n = 30) at > 12 h before surgery. All patients received standard perioperative multimodal analgesia (MMA). The primary endpoint was the pain intensity in the beginning 7 days after operation. The secondary endpoints were adverse reactions up to 7 days and incidence of CPSP at 3 months after surgery. RESULTS: Compared with placebos, the area under curves of visual analog scale (VAS) for 0-48 h after operation were significantly reduced in SDE group (143.3 ± 65.4 and 105.9 ± 36.3, P = 0.025). There were significantly fewer patients in the SDE group who had moderate-to-severe pain (VAS ≥ 4) (16.7% vs 50%; P = 0.012) at postoperative 48 h. Pain intensities were similar between the two groups at 72 h and 7 days postoperatively. The incidence of CPSP at 3 months was not different. SDE did not increase drug-related systemic adverse events. CONCLUSION: In addition to the standard perioperative MMA, a single-dose injection of long-acting κ-receptor agonist SDE provides significantly better pain management for 48 h following laparoscopic bariatric surgery. A long-acting κ-receptor agonist opioid could improve in-hospital pain management and potentiate early discharge after operation without increasing drug-related systemic complications.


Assuntos
Cirurgia Bariátrica , Dor Crônica , Laparoscopia , Obesidade Mórbida , Humanos , Analgésicos Opioides/uso terapêutico , Dor Crônica/etiologia , Obesidade Mórbida/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Método Duplo-Cego , Cirurgia Bariátrica/efeitos adversos , Laparoscopia/efeitos adversos
12.
J Exp Clin Cancer Res ; 42(1): 22, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36639681

RESUMO

BACKGROUND: Nitric oxide-releasing drugs are used for cardiovascular diseases; however, their effects on the tumor immune microenvironment are less clear. Therefore, this study explored the impact of nitric oxide donors on tumor progression in immune-competent mice. METHODS: The effects of three different nitric oxide-releasing compounds (SNAP, SNP, and ISMN) on tumor growth were studied in tumor-bearing mouse models. Three mouse tumor models were used: B16F1 melanoma and LL2 lung carcinoma in C57BL/6 mice, CT26 colon cancer in BALB/c mice, and LL2 lung carcinoma in NOD/SCID mice. After nitric oxide treatment, splenic cytokines and lymphocytes were analyzed by cytokine array and flow cytometry, and tumor-infiltrating lymphocytes in the TME were analyzed using flow cytometry and single-cell RNA sequencing. RESULTS: Low doses of three exogenous nitric oxide donors inhibited tumor growth in two immunocompetent mouse models but not in NOD/SCID immunodeficient mice. Low-dose nitric oxide donors increase the levels of splenic cytokines IFN-γ and TNF-α but decrease the levels of cytokines IL-6 and IL-10, suggesting an alteration in Th2 cells. Nitric oxide donors increased the number of CD8+ T cells with activation gene signatures, as indicated by single-cell RNA sequencing. Flow cytometry analysis confirmed an increase in infiltrating CD8+ T cells and dendritic cells. The antitumor effect of nitric oxide donors was abolished by depletion of CD8+ T cells, indicating the requirement for CD8+ T cells. Tumor inhibition correlated with a decrease in a subtype of protumor macrophages and an increase in a subset of Arg1-positive macrophages expressing antitumor gene signatures. The increase in this subset of macrophages was confirmed by flow cytometry analysis. Finally, the combination of low-dose nitric oxide donor and cisplatin induced an additive cancer therapeutic effect in two immunocompetent animal models. The enhanced therapeutic effect was accompanied by an increase in the cells expressing the gene signature of NK cell. CONCLUSIONS: Low concentrations of exogenous nitric oxide donors inhibit tumor growth in vivo by regulating T cells and macrophages. CD8+ T cells are essential for antitumor effects. In addition, low-dose nitric oxide donors may be combined with chemotherapeutic drugs in cancer therapy in the future.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma , Animais , Camundongos , Óxido Nítrico , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/uso terapêutico , Reposicionamento de Medicamentos , Camundongos Endogâmicos C57BL , Camundongos SCID , Citocinas , Microambiente Tumoral
15.
Front Oncol ; 12: 955313, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212420

RESUMO

Studies have reported the effects of the gut microbiota on colorectal cancer (CRC) chemotherapy, but few studies have investigated the association between gut microbiota and targeted therapy. This study investigated the role of the gut microbiota in the treatment outcomes of patients with metastatic CRC (mCRC). We enrolled 110 patients with mCRC and treated them with standard cancer therapy. Stool samples were collected before administering a combination of chemotherapy and targeted therapy. Patients who had a progressive disease (PD) or partial response (PR) for at least 12 cycles of therapy were included in the study. We further divided these patients into anti-epidermal growth factor receptor (cetuximab) and anti-vascular endothelial growth factor (bevacizumab) subgroups. The gut microbiota of the PR group and bevacizumab-PR subgroup exhibited significantly higher α-diversity. The ß-diversity of bacterial species significantly differed between the bevacizumab-PR and bevacizumab-PD groups (P = 0.029). Klebsiella quasipneumoniae exhibited the greatest fold change in abundance in the PD group than in the PR group. Lactobacillus and Bifidobacterium species exhibited higher abundance in the PD group. The abundance of Fusobacterium nucleatum was approximately 32 times higher in the PD group than in the PR group. A higher gut microbiota diversity was associated with more favorable treatment outcomes in the patients with mCRC. Bacterial species analysis of stool samples yielded heterogenous results. K. quasipneumoniae exhibited the greatest fold change in abundance among all bacterial species in the PD group. This result warrants further investigation especially in a Taiwanese population.

16.
J Clin Med ; 11(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36233806

RESUMO

Surgery for acute mesenteric infarction (AMI) is associated with high mortality. This study aimed to generate a mortality prediction model to predict the 30-day mortality of surgery for AMI. We included patients ≥18 years who received bowel resection in treating AMI and randomly divided into the derivation and validation groups. After multivariable analysis, the 'Surgery for acute mesenteric infarction mortality score' (SAMIMS) system was generated and was including age >62-year-old (3 points), hemodialysis (2 points), congestive heart failure (1 point), peptic ulcer disease (1 point), diabetes (1 point), cerebrovascular disease (1 point), and severe liver disease (4 points). The 30-day-mortality rates in the derivation group were 4.4%, 13.4%, 24.5%, and 32.5% among very low (0 point), low (1−3 point(s)), intermediate (4−6 points), and high (7−13 points)-risk patients. Compared to the very-low-risk group, the low-risk (OR = 3.332), intermediate-risk (OR = 7.004), and high-risk groups (OR = 10.410, p < 0.001) exhibited higher odds of 30-day mortality. We identified similar results in the validation group. The areas under the ROC curve were 0.677 and 0.696 in the derivation and validation groups. Our prediction model, SAMIMS, allowed for the stratification of the patients' 30-day-mortality risk of surgery for acute mesenteric infarction.

17.
Obes Surg ; 32(12): 3891-3899, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36205881

RESUMO

PURPOSE: Weight reduction decreases gastroesophageal reflux disease (GERD), but laparoscopic sleeve gastrectomy (LSG) that damages the structure of the stomach may worsen GERD. We aimed to elucidate the factors associated with increased severity of erosive esophagitis (EE) at 1 year after LSG. MATERIALS AND METHODS: Data on patients who underwent LSG between February 2007 and March 2016 were reviewed. Endoscopic findings and anthropometric data before and after surgery were recorded. The severity of EE was assessed according to the Los Angeles classification; severe EE was defined as grade C or D esophagitis. RESULTS: Totally, 316 patients were enrolled. Before LSG, 96 patients (30.4%) had grade A or B EE. One year after LSG, 215 patients (68%) had EE, including 136 (43%) with grade A, 62 (19.6%) with grade B, and 17 (5.4%) with grade C or D EE. One-hundred and twenty-seven of 220 patients (57.7%) without EE before LSG developed de novo EE following LSG. The incidence of severe EE after LSG in patients without pre-operative EE, grade A EE, or grade B EE at baseline was 3.2%, 6.8%, and 50%, respectively. Independent factors for an increased severity of EE after LSG were male gender (OR = 2.55, 95% CI = 1.52-4.28) and post-operative hiatal hernia (OR = 3.17, 95% CI = 1.66-6.06). CONCLUSION: The prevalence and severity of EE increased after LSG. Male gender and post-operative hiatal hernia are independent factors for an increased severity of EE after LSG. The incidence of severe EE after LSG is low for patients without pre-operative EE or grade A EE at baseline.


Assuntos
Esofagite , Refluxo Gastroesofágico , Hérnia Hiatal , Laparoscopia , Obesidade Mórbida , Úlcera Péptica , Humanos , Masculino , Feminino , Hérnia Hiatal/epidemiologia , Hérnia Hiatal/cirurgia , Hérnia Hiatal/complicações , Obesidade Mórbida/cirurgia , Laparoscopia/efeitos adversos , Gastrectomia/efeitos adversos , Esofagite/epidemiologia , Esofagite/etiologia , Esofagite/cirurgia , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/cirurgia , Úlcera Péptica/etiologia , Estudos Retrospectivos
18.
J Biomed Sci ; 29(1): 88, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36303164

RESUMO

BACKGROUND: Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. METHODS: Microbiota composition was determined through 16S rRNA V3-V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as "tri-part samples") in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. RESULTS: Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. CONCLUSION: This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.


Assuntos
Adenocarcinoma , Adenoma , Pólipos Adenomatosos , Neoplasias Colorretais , Humanos , Fusobacterium nucleatum/genética , Prevotella intermedia/genética , RNA Ribossômico 16S/genética , Meios de Cultivo Condicionados , Adenoma/genética , Adenoma/microbiologia , Adenoma/patologia , Neoplasias Colorretais/patologia , Transformação Celular Neoplásica/genética , Bactérias/genética , Adenocarcinoma/genética , Pólipos Adenomatosos/genética
19.
Allergy Asthma Proc ; 43(5): 435-445, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36065104

RESUMO

Background: Limited data exist on the clinical and economic burden of chronic rhinosinusitis with nasal polyposis (CRSwNP). Objective: To describe patient characteristics, health-care resource utilization (HCRU), and health-care costs among patients with CRSwNP with and without comorbid asthma (primary analysis) and with surgical management of nasal polyps (secondary analysis). Methods: This was a retrospective study of patients diagnosed with CRSwNP conducted using administrative claims data from January 1, 2013, through March 31, 2019. Study outcomes were assessed over a 2-year follow-up. Results were stratified by baseline asthma status (primary analysis) and presented separately for patients with surgically managed CRSwNP (secondary analysis). Results: The primary analysis included 10,999 patients with CRSwNP (2649 with asthma, 8350 without asthma). Patients with versus without asthma had higher medication use, HCRU, and all-cause medical costs (mean ± standard deviation $34,667 ± $42,234 versus $27,122 ± $45,573; p < 0.001) across the full follow-up period. CRSwNP-related medical costs were significantly higher for patients with versus without asthma in year 2 of follow-up. In the surgical management analysis (n = 4943), most categories of medication use and CRSwNP-related HCRU declined from baseline levels during follow-up, and CRSwNP-related pharmacy costs in year 2 were less than half of baseline levels. Conclusion: Patients diagnosed with CRSwNP and asthma had a greater burden of illness than those without asthma. Higher CRSwNP-related medical costs in year 2 of follow-up for patients with asthma may indicate worsening symptoms over time. Among patients with surgically managed CRSwNP, HCRU and costs increased in year 1 of follow-up but decreased below baseline levels in year 2, potentially reflecting improved symptom severity.


Assuntos
Asma , Pólipos Nasais , Rinite , Sinusite , Asma/tratamento farmacológico , Doença Crônica , Estresse Financeiro , Humanos , Revisão da Utilização de Seguros , Pólipos Nasais/complicações , Estudos Retrospectivos , Rinite/complicações , Rinite/epidemiologia , Sinusite/complicações
20.
Front Surg ; 9: 939857, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147694

RESUMO

Purpose: This study aims to identify the pre- and postoperative changes in the neutrophil-lymphocyte ratio (NLR) and its correlations to clinical characteristics in obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Method: Retrospectively, we included patients who has undergone LSG in our institution between January 2019 and April 2021. A total of 100 patients whose body mass index over 32.5 and received primary laparoscopic sleeve gastrectomy without infectious condition were included. Results: There was a significant decline in NLR (T0 vs. POM3 2.21 vs. 1.78, p = 0.005), neutrophil (T0 vs. POM3 5369 vs. 4050, p < 0.001) and lymphocyte count (T0 vs. POM3 2440: 2100, p < 0.001, respectively) at postoperative 3 months (POM3) compared to preoperative (T0) levels, but similar between POM3 and POM6. The declined counts (Neutrophile vs. Lymphocyte 1445.5/µl vs. 323.5/µl, p < 0.001) and percentage (Neutrophile vs. Lymphocyte 25.11% vs. 13.07%, p < 0.001) of neutrophile are higher than lymphocyte from T0 to POM3, but similar in POM3 and POM6. Preoperative NLR has a significant correlation with the preoperative body weight, preoperative insulin level, and excessive body weight loss (EBWL) at POM3. Preoperative NLR <2.36 had a sensitivity of 67.6% and a specificity of 62.5% in predicting successful weight loss (EBWL > 37.7%) at POM3 (AUC = 0.635, p = 0.032). Conclusion: There was a significant decline in NLR, neutrophil, and lymphocyte count from T0 to POM3, but similar between POM3 and POM6. The declined counts and percentage of neutrophile are higher than lymphocyte. Preoperative NLR shows the potential to be used as a prognostic biomarker for predicting successful weight loss at POM3 after LSG. Further studies could be designed to evaluate the value of prediction in successful outcome after LSG and figure out the relationship between the changes of neutrophil function and oncogenesis.

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