Assessing over decadal biomass burning influence on particulate matter composition in subequatorial Amazon: literature review, remote sensing, chemical speciation and machine learning application.

A study on aerosols in the Brazilian subequatorial Amazon region, Tangará da Serra (TS) and Alta Floresta (AF) was conducted and compared to findings in an additional site with background characteristics (Manaus, AM). TS and AF counties suffer from intense biomass burning periods in the dry season, and it accounts for high levels of particles in the atmosphere. Chemical characterization of fine and coarse particulate matter (PM) was performed to quantify water-soluble ions (WSI) and black carbon (BC). The importance of explanatory variables was assessed using three machine learning techniques. Average concentrations of PM in AF and TS were similar (PM2.0, 17±10 µg m-3 (AF) and 16±11 µg m-3 (TS) and PM10-2.0, 13±5 µg m-3 (AF) and 11±7 µg m-3 (TS)), but higher than the background site. BC and SO4 2- were the prevalent components as they represented 27%-68% of particulates chemical composition. The combination of the machine learning techniques provided a further understanding of the pathways for PM concentration variability, and the results highlighted the influence of biomass burning for key sample groups and periods. PM2.0, BC, and most WSI presented higher concentrations in the dry season, providing further support for the influence of biomass burning.

Association between the Lymphocyte-to-C-Reactive Protein Ratio and Survival Outcomes in Cancer Patients with GLIM-Defined Malnutrition: A Multicenter Study.

BACKGROUND AND AIMS: This study assessed the prognostic value of LCR in patients with cancer-associated malnutrition (CAM). Systemic inflammatory markers, particularly the lymphocyte-to-C-reactive protein ratio (LCR), are related to the survival of patients with CAM. The present retrospective analysis based on a prospective multicenter cohort study, which involved 1,437 hospitalized patients with CAM. METHODS: The area under the receiver operating characteristic curve (AUC) of ten inflammatory indicators-LCR, advanced lung cancer inflammation index, neutrophil-to-lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score, systemic immune-inflammation index, albumin-to-globulin ratio, LCR score, glucose-to-lymphocyte ratio, and platelet-to-lymphocyte ratio-were constructed. Nutritional status, blood markers, and quality of life (QoL) were evaluated within 48 h of admission. The overall survival (OS) was evaluated from September 1 to December 29, 2021. RESULTS: A total of 1,431 cancer patients diagnosed with malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Male patients were 62.8% of all, and the mean age was 60.66 years old. The AUC of LCR was higher than that of other inflammatory markers. The restricted cubic spline (RCS) of the Hazard ratios (HRs) showed an inverse L-shaped relationship with LCR. In addition, patients with low LCR had significantly poorer OS than those with high LCR. The addition of LCR to the model increased the predictive ability of 1-year mortality (AUC increase of 0.036), 3-year mortality (AUC increase of 0.038), and 5-year mortality (AUC increase of 0.031). CONCLUSIONS: Assessing the LCR can help the medical staff identify cancer patients with nutritional deficiency at high risk of oncological outcomes and develop individualized therapeutic strategies.

Blood plasma proteome alteration after local tissue damage induced by Bothrops erythromelas snake venom in mice.

Snakes of the genus Bothrops are responsible the most snakebites in the Brazil, causing a diverse and complex pathophysiological condition. Bothrops erythromelas is the main specie of medical relevance found in the Caatinga from the Brazilian Northeast region. The pathophysiological effects involving B. erythromelas snakebite as well as the organism reaction in response to this envenomation are not so explored. Thus, edema was induced in mice paws using 2.5 µg or 5.0 µg of B. erythromelas venom, and the percentage of edema was measured. Plasma was collected 30  minutes after the envenomation-induced in mice and analyzed by mass spectrometry. It was identified a total of 112 common plasma proteins differentially abundant among experimental groups, which are involved with the complement system and coagulation cascades, oxidative stress, neutrophil degranulation, platelets degranulation and inflammatory response. Apolipoprotein A1 (Apoa), serum amyloid protein A-4 (Saa4), adiponectin (Adipoq) showed up-regulated in mice plasma after injection of venom, while fibulin (Fbln1), factor XII (F12) and vitamin K-dependent protein Z (Proz) showed down-regulated. The results indicate a protein pattern of thrombo-inflammation to the B. erythromelas snakebite, evidencing potential biomarkers for monitoring this snakebite, new therapeutic targets and its correlations with the degree of envenomation once showed modulations in the abundance among the different groups according to the amount of venom injected into the mice.

Evaluating the impact of metformin targets on the risk of osteoarthritis: a mendelian randomization study.

OBJECTIVE: To provide some causal evidence concerning the effects of metformin on osteoarthritis (OA) using two metformin targets, namely AMP-activated protein kinase (AMPK) and growth differentiation factor 15 (GDF-15) as metformin proxies. METHODS: This is a 2-sample Mendelian randomization design. We constructed 44 AMPK-related variants genetically predicted in HbA1c (%) as instruments for AMPK and five variants strongly predicted GDF-15 as instruments for GDF-15. Summary-level data for three OA phenotypes, including OA at any site, knee OA, and hip OA were obtained from the largest genome-wide meta-analysis across the UK Biobank and arcOGEN with 455,211 Europeans. Main analyses were conducted using the inverse-variance weighted method. Weighted median and MR-Egger were conducted as sensitivity analyses to assess the robustness of our results. RESULTS: Genetically predicted AMPK were negatively associated with OA at any site (OR: 0.60; 95% CI: 0.43-0.83) and hip OA (OR: 0.42; 95% CI: 0.22-0.80), but with not knee OA (OR: 0.85; 95% CI: 0.49-1.50). Higher levels of genetically predicted GDF-15 reduced the risk of hip OA (OR: 0.95; 95% CI: 0.90-0.99), but not OA at any site (OR: 1.00; 95% CI: 0.98-1.02) and knee OA (OR: 1.02; 95% CI: 0.98-1.07). CONCLUSION: This study indicates that AMPK and GDF-15 can be potential therapeutic targets for OA, especially for hip OA, and metformin would be repurposed for OA therapy which needs to be verified in randomized controlled trials.

Synovitis mediates the association between bone marrow lesions and knee pain in osteoarthritis: data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium.

OBJECTIVES: Although subchondral bone marrow lesions (BMLs) and synovitis have been well acknowledged as important sources of pain in knee osteoarthritis (KOA), it is unclear if synovitis plays the mediating role in the relationship between BMLs and knee pain. METHODS: We analyzed 600 subjects with magnetic resonance imaging (MRI) in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort at baseline and 24-month. BMLs and synovitis were measured according to the MRI Osteoarthritis Knee Score (MOAKS) scoring system. BMLs were scored in five subregions. A summary synovitis score of effusion and Hoffa-synovitis was calculated. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression models were applied to analyze the natural direct effect (NDE) of BMLs and synovitis with knee pain, respectively, and natural indirect effect (NIE) mediated by synovitis. RESULTS: 590 participants (58.8% females, with a mean age of 61.5) were included in the present analyses. For NDE, knee pain was cross-sectionally associated with medial femorotibial BMLs (ß = 0.23, 95% CI: 0.09, 0.38) and synovitis (ß = 0.40, 95% CI: 0.20, 0.60). Longitudinal associations retained significant [medial femorotibial BMLs (ß = 0.37, 95% CI: 0.21, 0.53); synovitis (ß = 0.72, 95% CI: 0.45, 0.99)]. In the NIE analyses, synovitis mediated the association between medial femorotibial BML and knee pain at baseline (ß = 0.051, 95% CI: 0.01, 0.09) and over 24 months (ß = 0.079, 95% CI: 0.023, 0.15), with the mediating proportion of 17.8% and 22.4%, respectively. CONCLUSION: Synovitis partially mediates the association between medial femorotibial BMLs and knee pain.

The interactions between MRI-detected osteophytes and bone marrow lesions or effusion-synovitis on knee symptom progression: an exploratory study.

OBJECTIVES: To investigate the longitudinal association between MRI-detected osteophyte scores and progression of knee symptoms, and whether the association was modified in the presence of bone marrow lesions (BMLs) or effusion-synovitis. METHODS: Data from Vitamin D Effects on Osteoarthritis (VIDEO) study, a randomized, double-blinded and placebo-controlled clinical trial in symptomatic knee osteoarthritis (OA) patients, were analyzed as an exploratory study. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess knee symptoms. Osteophytes, BMLs and effusion-synovitis were measured using MRI. RESULTS: 334 participants with MRI information and WOMAC score (baseline and follow-up) were included in the analyses, with 24.3% of them having knee pain increased 2 years later. Statistically significant interactions were found between MRI-detected osteophytes and BMLs or effusion-synovitis on increased knee symptoms. In participants with BMLs, higher baseline scores of MRI-detected osteophytes in most compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and effusion-synovitis. In participants with effusion-synovitis, higher baseline scores of MRI-detected osteophytes in almost all the compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and BMLs. In contrast, MRI-detected osteophyte scores were generally not associated with knee symptom progression in participants without baseline BMLs or effusion-synovitis. CONCLUSIONS: MRI-detected OPs are associated with increased total knee pain, weight-bearing knee pain, stiffness and physical dysfunction in participants presenting BMLs or effusion-synovitis, but not in participants lacking BMLs or effusion-synovitis. This suggests they could interact with bone or synovial abnormalities to induce symptoms in knee OA.

[Reoperation rate and related factors in patients with Crohn's disease].

Objective: To analyze the cumulative reoperation rate of postoperative Crohn's disease (CD) patients and investigate the operation reasons and the effects of drugs on surgical recurrence. Method: Patients with Crohn's disease who had undergone intestinal resection from January 2000 to March 2020 in Peking Union Medical College Hospital were enrolled. Patients were divided into reoperation and non-reoperation group according to whether they had a second operation. And the basic characteristics and the reasons for the primary and second operation were retrospectively analyzed. Meanwhile, patients were divided into low-risk reoperation group and high-risk group based on risk stratification. Kaplan-Meier methods were performed to analyze the cumulative surgical recurrence rate and to compare the recurrence rate in different risk stratification and chi-square tests was used to analyze the effects of different maintenance drugs on reoperation. Result: A total of 160 patients were enrolled in the study. There were 110 males and 50 females, and the age at first operation was (35.6±14.1) years old. There were 40 patients in the reoperation group and 120 patients in the non-reoperation group. According to univariate analysis, the proportion of male gender(P=0.030), penetrating phenotype(P<0.001), history of appendectomy before the primary surgery(P=0.035) and no postoperative maintenance therapy (P<0.001) were higher in surgical recurrence group. In terms of the operation reasons, intestinal obstruction accounted for the highest proportion in the primary operation (26.9%, 43/160), while the intestinal fistula was the most common reason for reoperation (42.5%, 17/40). After the primary surgery, the cumulative reoperation rates at 1, 3, 5 and 10 years were 5.9% (9 cases), 12.3% (17 cases), 21.8% (25 cases) and 37.6% (34 cases), respectively. The ten years cumulative reoperation rate of the high-risk group was 42.8% (31 cases), which was much higher than that of low-risk group (19.8%, 3 cases), and the difference was statistically significant (P=0.006). There was no statistically significant difference in the surgical recurrence rate of low-risk group patients(P=0.076)whether maintenance therapies were added or not, while the recurrence rate of high-risk group patients who did not receive maintenance therapy was higher than those who received immunosuppressant with or without (±) 5-aminosalicylic acid (ASA) (P=0.001) and biological agent±5-ASA (P=0.001), and the difference was statistically significant. Conclusion: Patients with CD are still at risk of reoperation after surgery. Immunosuppressive agents and biologics can prevent patients from reoperation in high-risk groups.

[The 488th case: chronic diarrhea and abnormal liver function].

A 56-year-old female was admitted to Department of Gastroenterology at Peking Union Medical College Hospital with diarrhea for seven months, and abnormal liver function for six months. She had a history of type 1 diabetes. The main clinical manifestations were recurrent fatty diarrhea and abnormal liver function, accompanied by abdominal and retroperitoneal lymphadenopathy, elevated CA19-9 and CEA. Progressive impairment of hepatic synthetic function and shrinkage of liver developed in a short period of time. The pathology of liver biopsy suggested that nodular regeneration of hepatocytes was followed by hyperplasia of thin bile ducts after submassive necrosis. Intestinal mucosa biopsies were performed twice. The pathology showed that the intestinal villi were completely blunt, accompanied with crypt hyperplasia. Goblet cells disappeared with reduced mucin. Paneth cells were barely seen without intraepithelial infiltration of lymphocytes. Rifaximin was not effective, while glucocorticoids improved clinical situation. The diagnosis of autoimmune enteropathy was finally confirmed by multidisciplinary team including departments of gastroenterology, pathology, endocrinology, hematology, infectious diseases, and rheumatology. With the administration of glucocorticoid and sirolimus, diarrhea relieved and liver function returned to normal.

Comparison of the clinical and CT features between COVID-19 and H1N1 influenza pneumonia patients in Zhejiang, China.

OBJECTIVE: To explore the different clinical and CT features distinguishing COVID-19 from H1N1 influenza pneumonia. PATIENTS AND METHODS: We compared two independent cohorts of COVID-19 pneumonia (n=405) and H1N1 influenza pneumonia (n=78), retrospectively. All patients were confirmed by RT-PCR. Four hundred and five cases of COVID-19 pneumonia were confirmed in nine hospitals of Zhejiang province, China from January 21 to February 20, 2020. Seventy-eight cases of H1N1 influenza pneumonia were confirmed in our hospital from January 1, 2017 to February 29, 2020. Their clinical manifestations, laboratory test results, and CT imaging characteristics were compared. RESULTS: COVID-19 pneumonia patients showed less proportions of underlying diseases, fever and respiratory symptoms than those of H1N1 pneumonia patients (p<0.01). White blood cell count, neutrophilic granulocyte percentage, C-reactive protein, procalcitonin, D-Dimer, and lactate dehydrogenase in H1N1 pneumonia patients were higher than those of COVID-19 pneumonia patients (p<0.05). H1N1 pneumonia was often symmetrically located in the dorsal part of inferior lung lobes, while COVID-19 pneumonia was unusually showed as a peripheral but non-specific lobe distribution. Ground glass opacity was more common in COVID-19 pneumonia and consolidation lesions were more common in H1N1 pneumonia (p<0.01). COVID-19 pneumonia lesions showed a relatively clear margin compared with H1N1 pneumonia. Crazy-paving pattern, thickening vessels, reversed halo sign and early fibrotic lesions were more common in COVID-19 pneumonia than H1N1 pneumonia (p<0.05). Pleural effusion in COVID-19 pneumonia was significantly less common than H1N1 pneumonia (p<0.01). CONCLUSIONS: Compared with H1N1 pneumonia in Zhejiang, China, the clinical manifestations of COVID-19 pneumonia were more concealed with less underlying diseases and slighter respiratory symptoms. The more common CT manifestations of COVID-19 pneumonia included ground-glass opacity with a relatively clear margin, crazy-paving pattern, thickening vessels, reversed halo sign, and early fibrotic lesions, while the less common CT manifestations of COVID-19 pneumonia included consolidation and pleural effusion.

[Analysis on clinical features of patients with ulcerative colitis associated colorectal cancer].

Objective: To analyze the clinical features of ulcerative colitis associated colorectal cancer (UC-CRC). Methods: A total of 869 inpatients with Ulcerative Colitis (UC) in Peking Union Medical Hospital from January 1998 to January 2018 were continuously enrolled. Clinical data and the outcome of colorectal cancer (CRC) were collected via medical records and telephone follow-up. Chi-square test and logistic regression model were used to analyze the data. Results: There were 16 patients in 869 UC inpatients who were diagnosed with CRC during a period of 7 548 person years and the incidence rate of UC-CRC was 1.84%. Compared to UC inpatients without CRC, a longer course of disease (OR=1.087, 95% CI:1.046-1.129) , a lower usage rate of 5-Aminosalicylic Acid(5-ASA) (OR=0.218, 95% CI:0.052-0.915) and a higher incidence rate of intestinal stenosis (OR=16.533, 95% CI:3.824-71.478) were found in UC inpatients with CRC. Conclusions: A long disease course is a risk factor for UC patients developing CRC, while 5-ASA therapy can reduce the risk of suffering from CRC. For UC patients with intestinal stenosis, CRC should be warned for occurring.

Evaluation of a second-generation monoenergetic reconstruction algorithm for lesion contrast and venous invasion in pancreatic ductal adenocarcinomas.

OBJECTIVE: At lower energy levels, virtual monochromatic imaging by dual-energy computed tomography improves lesion attenuation but produces greater image noise with the conventional monoenergetic reconstruction algorithm (Mono). Recently, a second-generation algorithm (Mono+) was introduced to overcome this limitation. We compared the quality of images obtained with these algorithms and investigated the optimal energy selection for pancreatic ductal adenocarcinomas (PDACs). PATIENTS AND METHODS: Image data from 54 PDAC cases were generated at 40, 50, 60, 70, and 80 keV using Mono and Mono+. Image quality was objectively assessed by comparing the signal-to-noise ratios (SNRs), noise, and the contrast-to-noise ratios (CNRs) at different keV levels and between these algorithms at the same keV level. Lesion conspicuity and venous invasion were subjectively assessed. RESULTS: For Mono, the mean pancreas and tumour SNRs peaked at 70 keV (p<0.001). The noise increased as the energy level decreased (p<0.001). CNRtumour remained unchanged. For Mono+, the mean pancreas SNR peaked at 40 keV (p<0.001). The mean tumour SNR and noise remained unchanged. The tumour CNRs were highest at 40 keV (4.9 times the CNR of Mono 40 keV, p<0.001). Subjectively, lesion conspicuity was best at Mono+ 40 keV (p<0.001) and it showed higher diagnostic performance levels on venous invasion assessment against Mono. CONCLUSIONS: Mono+ produced better image quality, and 40 keV is recommended for the diagnosis of PDAC.

Associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage enzymes in patients with knee osteoarthritis.

OBJECTIVE: Animal studies suggest that S100A8/S100A9 may be involved in the pathogenesis of osteoarthritis (OA); however, there has been no clinical study examining the associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage degradation enzymes in knee OA patients so far. Therefore, this study was designed to investigate the cross-sectional associations between serum levels of S100A8/S100A9 and the outcomes in patients with knee OA. DESIGN: A total of 141 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess joint symptoms. Magnetic resonance imaging (MRI) was used to measure knee structural abnormalities including cartilage defects. Knee radiography was used to assess joint space narrowing (JSN), osteophytes and the radiographic severity of OA. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of S100A8/S100A9, matrix metalloproteinase (MMP)-3, MMP10 and MMP13. RESULTS: In multivariable analyses, serum S100A8/S100A9 were positively associated with total WOMAC score (ß: 0.111 per 10 ng/ml, P = 0.021), WOMAC weight-bearing pain (ß: 0.015 per 10 ng/ml, P = 0.043) and WOMAC physical dysfunction (ß: 0.091 per 10 ng/ml, P = 0.010), and had positive associations with total cartilage defects and cartilage defects at lateral femoral, lateral tibial and medial femoral sites (ORs: 1.006-1.008 per 10 ng/ml, all P < 0.05) and serum levels of MMP3 (ß: 0.002 per 10 ng/ml, P = 0.032) in patients with clinical knee OA. CONCLUSIONS: Serum levels of S100A8/S100A9 were positively associated with increased knee symptoms, cartilage defects and serum cartilage degradation enzymes in patients with knee OA, suggesting that S100A8/S100A9 may have a role to play in knee OA. Future longitudinal studies are required to confirm these findings.

Associations between knee structural measures, circulating inflammatory factors and MMP13 in patients with knee osteoarthritis.

OBJECTIVE: To investigate cross-sectional associations between serum level of Matrix metalloproteinase (MMP)13 and knee structural measures and circulating inflammatory factors in patients with symptomatic knee osteoarthritis (OA). DESIGN: A total of 149 subjects with symptomatic knee OA were included. Magnetic resonance imaging was used to measure infrapatellar fat pad (IPFP) volume, IPFP signal intensity alternation, cartilage volume and cartilage defects. Knee radiography was used to assess radiographic OA using the Kellgren-Lawrence (K-L) grading system. Enzyme-linked immunosorbent assay was used to measure the serum levels of inflammatory factors and MMP13. RESULTS: In multivariable analyses, serum MMP13 was negatively associated with cartilage volume at patellar site (ß: -32.94 mm3 per 10 ng/ml, P < 0.05), and positively associated with cartilage defect at medial femoral site (OR: 1.13 per 10 ng/ml, P < 0.05). Also, MMP13 was positively associated with K-L grading and IPFP signal intensity alteration (OR: 1.14 and 1.15 per 10 ng/ml, respectively, both P < 0.05), and negatively associated with IPFP volume (ß: -0.34 cm3 per 10 ng/ml, P < 0.05). Furthermore, serum level of adiponectin was negatively associated serum MMP13 quartiles (OR: 0.66 per 10 µg/ml, P < 0.05), and serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-8 and IL-18 were positively associated with serum MMP13 quartiles (ORs: 1.01-1.18 per 10 pg/ml, all P < 0.05). CONCLUSIONS: Serum level of MMP13 was associated with knee structural abnormalities as well as serum inflammatory factors. These suggest that systemic MMP13 may play a role in knee OA, and could be regulated by inflammatory factors.

Lyophilized bone marrow cell extract functionally restores irradiation-injured salivary glands.

OBJECTIVE: Bone marrow cell extract (BMCE) was previously reported to restore salivary gland hypofunction caused by irradiation injury. Proteins were shown to be the main active factors in BMCE. However, BMCE therapy requires multiple injections and protein denaturation is a concern during BMCE storage. This study aimed to preserve, by lyophilization (freeze-drying), the bioactive factors in BMCE. METHODS: We developed a method to freeze-dry BMCE and then to analyze its ingredients and functions in vivo. Freeze-dried (FD) BMCE, freshly prepared BMCE (positive control), or saline (vehicle control) was injected into the tail vein of mice that had received irradiation to damage their salivary glands. RESULTS: Results demonstrated that the presence of angiogenesis-related factors and cytokines in FD-BMCE remained comparable to those found in fresh BMCE. Both fresh and FD-BMCE restored comparably saliva secretion, increased cell proliferation, upregulated regenerative/repair genes, protected salivary acinar cells, parasympathetic nerves, and blood vessels from irradiation-damaged salivary glands. CONCLUSION: Lyophilization of BMCE maintained its bioactivity and therapeutic effect on irradiation-injured salivary glands. The advantages of freeze-drying BMCE are its storage and transport at ambient temperature.

Chicken egg-white extracts promote OCT4 and NANOG expression and telomeres growth in 293T cells.

It will have broad applications in cell biology if one of egg cell extracts has the roles to promote cell proliferation and reprogramming. It will provide a new method for easier reprogramming somatic cells and promote cell proliferation. We found chicken egg-white extracts have roles to promote cell proliferation and reprogramming. The different ingredients were then assessed for cell proliferation activity and somatic cell reprogramming. Chicken egg-white extract ingredients that were less than 3 kDa (LT3K) promoted cell proliferation. Those ingredients that were greater than 3 kDa (GT3K) promoted the increased expression of pluripotency factors in somatic cells and promote telomeres growth in 293T cells. Chicken egg-whites can be separated into ingredients of LT3K, which act to promote cell proliferation, and GT3K, which can be used to promote somatic cell reprogramming.

Associations between serum ghrelin and knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee osteoarthritis.

OBJECTIVE: The roles of ghrelin in knee osteoarthritis (OA) are unclear. This study aimed to examine cross-sectional associations of ghrelin with knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee OA. METHODS: This study included 146 patients with symptomatic knee OA. Serum levels of ghrelin and cartilage or bone biomarkers including cartilage oligomeric matrix protein (COMP), cross linked C-telopeptide of type I collagen (CTXI), cross linked N-telopeptide of type I collagen (NTXI), N-terminal procollagen III propeptide (PIIINP), and matrix metalloproteinase (MMP)-3, 10, 13 were measured using Enzyme-linked immunosorbent assay (ELISA). Knee symptoms were assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Infrapatellar fat pad (IPFP) volume, IPFP signal intensity alternation, cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis were assessed using the (MRI). Osteophytes and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. RESULTS: After adjustment for potential confounders, ghrelin quartiles were positively associated with knee symptoms including pain, stiffness, dysfunction and total score (quartile 4 vs 1: ß 24.19, 95% CI 8.13-40.25). Ghrelin quartiles were also significantly associated with increased IPFP signal intensity alteration (quartile 4 vs 1: OR 3.57, 95% CI 1.55-8.25) and NTXI, PIIINP, MMP3 and MMP13. Ghrelin was not significantly associated with other joint structures and biomarkers. CONCLUSIONS: Serum levels of ghrelin were significantly associated with increased knee symptoms, IPFP signal intensity alteration and serum levels of MMP3, MMP13, NTXI and PIIINP, suggesting that ghrelin may have a role to play in knee OA.

[Prognostic significance of early assessment of minimal residual disease in acute myeloid leukemia with mutated NPM1 patients].

Objective: To explore prognostic significance of early assessment of minimal residual leukemia (MRD) in adult patients with de novo acute myeloid leukemia (AML) with mutated NPM1. Methods: The response, NPM1 mutated transcript level after induction chemotherapy and the first 2 cycles of consolidation chemotherapy, disease-free survival (DFS) and overall survival (OS) in 137 patients with AML with NPM1 mutations of A, B and D were retrospectively analyzed. Results: Data of 137 patients were collected, 67 were male, the median age was 49 years (16-67 years) , 107 (78.1%) had normal karyotype, 57 (41.6%) had positive FLT3-ITD mutation, the median NPM1 mutated transcript level at diagnosis was 84.1%. Among the 134 evaluable patients, 115 (85.8%) achieved a complete remission (CR) . Multivariate analyses revealed that WBC<100×10(9)/L (OR=0.3, 95% CI 0.1-0.9, P=0.027) and first induction therapy with "IA10" protocol (OR=0.3, 95% CI 0.1-0.8, P=0.015) were factors associated with achieving a CR. With a median follow-up period of 24 months (range, 2 to 91 months) in 77 survived CR patients, the probabilities of DFS and OS at 3 years were 48.0% and 63.9%, respectively. Multivariate analyses showed that positive FLT3-ITD (HR=3.2, 95% CI 1.6-6.7, P=0.002) , high MRD level after 2 cycles of consolidation chemotherapy (NPM1 mutation transcript level <3-log reduction from the individual baseline, HR=23.2, 95% CI 7.0-76.6, P<0.001) and chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT) rather than allogeneic HSCT (allo-HSCT) (HR=2.6, 95% CI 1.0-6.6, P=0.045) were the unfavorable factors affecting DFS, high MRD level at the time of achieving the first CR (NPM1 mutation transcript level <2-log reduction from the individual baseline, OR=2.5, 95% CI 1.0-6.1, P=0.040) and after 2 cycles of consolidation chemotherapy (HR=4.5, 95% CI 2.0-10.3, P<0.001) were the unfavorable factors affecting OS. Furthermore, DFS and OS rates at 3 years in those receiving chemotherapy or auto-HSCT were 39.7% and 59.1%, respectively; positive FLT3-ITD and high MRD level after 2 cycles of consolidation chemotherapy were independent factors associated with both shorter DFS (HR=3.5, 95% CI 1.6-7.6, P=0.002 and HR=8.9, 95% CI 3.8-20.7, P<0.001) and OS (HR=2.7, 95% CI 1.1-6.9, P=0.036 and HR=3.1, 95% CI 1.2-8.0, P=0.021) ; meanwhile, high MRD level at the time of achieving the first CR associated with shorter OS (HR=3.1, 95% CI 1.2-8.0, P=0.022) . Conclusion: Positive FLT3-ITD mutation and high MRD level after induction or consolidation chemotherapy associated with poor outcomes in AML patients with mutated NPM1.