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STUDY OBJECTIVES: We investigated the therapeutic effects of exercise in patients with obstructive sleep apnea (OSA), aiming to identify the subgroups that benefit the most and determine the optimal exercise protocol. METHODS: Major databases were searched for randomized controlled trials involving patients with OSA performing aerobic exercise and/or resistance training. The investigated outcomes included apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), body mass index (BMI), and peak oxygen consumption during exercise (VO2peak). The pre- and postintervention unstandardized mean difference (USMD) of these parameters was compared between the exercise and control groups. RESULTS: Twelve studies involving 526 patients were included. Exercise training significantly reduced AHI (USMD = -7.08 events/hour, 95% confidence interval [CI]: -9.98 to -4.17, p < 0.00001), ESS (USMD = -2.37, CI: -3.21 to -1.54, p < 0.00001), and BMI (USMD = -0.72 kg/m2, CI: -1.22 to -0.22, p = 0.005) and enhanced VO2peak (USMD = 3.46 mL/kg/min, CI: 1.20 to 5.71, p = 0.003). Subgroup analyses revealed that in continuous positive airway pressure (CPAP)-adherent patients, exercise significantly improved VO2peak but did not reduce AHI and ESS. A trend was observed that combining resistance training with aerobic exercise resulted in greater AHI reduction and VO2peak enhancement. Notably, exercise improved AHI, ESS, BMI, and VO2peak regardless of the baseline AHI or BMI. CONCLUSIONS: Exercise, including resistance and aerobic training, should be part of treatment for patients with OSA of all severities, regardless of obesity status, and even for those who are already under CPAP. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered with the PROSPERO database (#CRD42023423527).

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This study aimed to explore the efficacy of single and combined effects of exercise and branched-chain amino acid (BCAA) supplements on improving frailty and quality of life in older adults. In total, 120 study participants were allocated into a combined exercise-and-BCAA supplementation group, an exercise-only group, a BCAA supplementation-only group, and a control group. Results showed that Fried's frailty score significantly decreased in the combined exercise-and-BCAA supplementation group (ß= -1.73, p<0.001), exercise-only group (ß= -1.68, p<0.001), and BCAA supplementation-only group (ß= -0.73, p=0.005) compared to the control group. Moreover, the combination of exercise and BCAA supplements and the exercise-only program produced significant improvements in frailty compared to the BCAA supplement-only group and control group (p<0.05). Exercise should be a critical approach for older adults to improve frailty. Healthcare professionals in geriatric care should incorporate exercise programs as frailty management and prevention for older adults.

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BACKGROUND: Ramucirumab is indicated for salvage treatment after failure of first-line treatment for metastatic colorectal cancer (mCRC). However, the application of ramucirumab at later-line treatment in real-world practice has not received much discussion. METHODS: In this retrospective study, we enrolled 70 patients with mCRC who received ramucirumab plus chemotherapy at National Taiwan University Hospital between 2018 and 2019. RESULTS: Compared with those who received third- or later-line ramucirumab treatment, patients who received second-line ramucirumab treatment had significantly longer median time to treatment discontinuation (mTTD; 6.7 vs 3.6 months, P = .004) and median overall survival (mOS; not reached vs 7.6 months, P = .009). Multivariate analyses revealed that second-line ramucirumab and triplet chemotherapy backbone were the only independent predictive factors for long mTTD and mOS. Patients who received ramucirumab with triplet chemotherapy had a significantly longer mOS than did patients who received ramucirumab with doublet chemotherapy (not reached vs 5.6 months, P = .002). Among those receiving second-line ramucirumab treatment, combination with triplet chemotherapy led to a longer mTTD than did combination with doublet chemotherapy, but the difference was non-significant (not reached vs 4.4 months, P = .108). By contrast, in patients receiving fourth- or later-line ramucirumab, combination with triplet chemotherapy led to significantly longer mTTD than did combination with doublet chemotherapy (8.0 vs 2.9 months, P = .032). CONCLUSION: Ramucirumab plus triplet chemotherapy may be an alternative regimen in patients with mCRC, particularly as a later-line treatment modality.

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BACKGROUND: A new strategy, particularly a novel combination, for immunotherapy in microsatellite stable metastatic colorectal cancer (mCRC) treatment needs to be formulated. Studies on the interferon-γ (IFN-γ)/ Janus kinase (JAK)/ signal transducer and activator of transcription (STAT)1 pathway provide new directions in this regard. METHODS: Our study applies three colon cancer cell lines, including microsatellite stable (MSS) cell lines, which are SW480 and SW620, and microsatellite instability-high (MSI-H) cell line, which is DLD-1. We compared the expressions of immune surface markers on colon cancer cells in response to IFN-γ. We elucidated these mechanisms, which involved the upregulation of immune surface markers. Furthermore, we examined real-world clinical samples using the PerkinElmer Opal multiplex system and NanoString analysis. RESULTS: We established that the baseline expression of major histocompatibility complex (MHC) class I alleles and programmed death-ligand 1 (PD-L1) were generally low in cell line models. The immune surface markers were significantly increased after IFN-γ stimulation on SW480 but were notably unresponsive on the SW620 cell line. We discovered that STAT1 and phosphorylated STAT1 (pSTAT1) were downregulated in the SW620 cell line. We verified that the STAT1/pSTAT1 could be restored through the application of proteasome inhibitors, especially bortezomib. The expression of MHC class I as downstream signals of STAT1 was also up-regulated by proteasome inhibitors. The similar results were reproduced in DLD-1 cell line, which was also initially unresponsive to IFN-γ. In real-world samples of patients with mCRC, we found that higher STAT1 expression in tumor cells was strongly indicative of a highly immunogenic microenvironment, with significantly higher expression levels of MHC class I and PD-L1, not only on tumor cells but also on non-tumor cells. Furthermore, tumor infiltrating lymphocytes (TILs) were increased in the positive-STAT1 group. Through NanoString analysis, we confirmed that the mRNA expressions of IFN-γ, human leukocyte antigen (HLA)-A, HLA-E, and HLA-G were also significantly higher in the positive-STAT1 group than those in the negative-STAT1 group. CONCLUSION: Our study provides a novel rationale for the addition of bortezomib, a proteasome inhibitor, into new immunotherapy combinations.

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Single immunotherapy fails to demonstrate efficacy in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Research on immune reactions before and after systemic agents for mCRC is warranted. Our study examined cell line models to compare the expression of immune surface markers on colon cancer cells before and after chemotherapy agents. We also elucidated mechanisms underlying the effects of chemotherapy agents on immune surface markers. We used real-world clinical samples with NanoString analysis and the Perkin-Elmer Opal multiplex system. We established that chemotherapy agents, particularly 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, stimulated the expression of stimulatory MHC class I alleles through stimulation the pathway of transporters associated with antigen processing 1 and 2 (TAP1 and TAP2) in cell line models. Application of infected cell protein 47 (ICP-47), a specific inhibitor of the TAP1/TAP2, significantly inhibited expression of TAP1/TAP2 and also inhibited the expression of the downstream MHC class I. In the functional assay, SN-38 significantly promoted the phagocytosis of colon cancer cells by monocyte-derived dendritic cells (MoDCs). We confirmed that the expression of major histocompatibility complex (MHC) class I, significantly increased after first-line chemotherapy and targeted therapy in the samples of real-world patients with de novo mCRC. Our study provides new insights for novel immunotherapy combinations.

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To investigate the prognostic significance of metabolic parameters and texture analysis on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in patients with breast invasive ductal carcinoma (IDC), from August 2005 to May 2015, IDC patients who had undergone pre-treatment FDG PET/CT were enrolled. The metabolic parameters, including maximal standardized uptake value of breast tumor (SUVbt) and ipsilateral axillary lymph node (SUVln), metabolic tumor volume (MTVbt) and total lesion glycolysis (TLGbt) of breast tumor, whole-body MTV (MTVwb) and whole-body TLG (TLGwb) were recorded. Nine textural features of tumor (four co-occurrence matrices and five SUV-based statistics) were measured. The prognostic significance of above parameters and clinical factors was assessed by univariate and multivariate analyses. Thirty-five patients were enrolled. Patients with low and high MTVwb had 5-year progression-free survival (PFS) of 81.0 and 14.3% (p < 0.0001). The 5-year overall survival for low and high MTVwb was 88.5% and 43.6% (p = 0.0005). Multivariate analyses showed MTVwb was an independent prognostic factor for PFS (HR: 8.29, 95% CI: 2.17-31.64, p = 0.0020). The SUV, TLG and textural features were not independently predictive. Elevated MTVwb was an independent predictor for shorter PFS in patients with breast IDC.

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Autoimmune pancreatitis (AP) is a rare autoimmune pancreatic manifestation of systemic immunoglobulin G4 (IgG4)-related sclerosing disease. Distinguishing between AP and pancreatic cancer is crucial because the clinical courses, treatments, and prognoses of these two disease entities are quite different. We herein report a case involving a 52-year-old man with subacute epigastralgia who visited our hospital for evaluation of a suspicious pancreatic mass found during esophagogastroduodenoscopy. Enhanced computed tomography (CT) revealed an enlarged lesion in the pancreatic head with encasement of hepatic vessels. The lesion also exhibited increased 18F-fluorodeoxyglucose accumulation on positron emission tomography/CT imaging, which was highly suggestive of pancreatic cancer. After open biopsy, morphologic examination showed an inflammatory infiltrate in the pancreas, which was compatible with chronic sclerotic pancreatitis. Further laboratory tests revealed an elevated serum IgG4 level, and the diagnosis of sclerotic pancreatitis was then confirmed. After corticosteroid treatment, the pancreatic lesion showed shrinkage on follow-up CT, and the serum IgG4 titer decreased to the normal range. This case suggests that clinicians should be familiar with the clinical presentations and diagnostic criteria of AP versus pancreatic cancer. An awareness of the differences between these diseases may avoid misdiagnosis and unnecessary surgical intervention.

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PURPOSE: The purpose of this study was to determine the prognostic significance of metabolic parameters on pre-treatment 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/CT), in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-containing therapy. MATERIALS AND METHODS: From September 2009 to December 2014, DLBCL patients who had received FDG PET/CT scans for staging were enrolled. The maximal standardized uptake value of tumor (SUVt) was recorded. The metabolic tumor volume (MTV) was the volume of lesion with an elevated SUV greater than 2.5. The total lesion glycolysis (TLG) was the sum of the products of MTV and mean SUV in all measured lesions. Univariate and multivariate analyses were used to assess the prognostic significance of maximal SUVt, total MTV, TLG and other clinical parameters. RESULTS: There were 118 patients enrolled in this study. The median follow-up time was 28.7 months. The 5-year progression-free survival (PFS) for patients with higher and lower total MTV was 32.3% and 66.0% respectively (p = 0.0001). The 5-year overall survival (OS) for patients with higher and lower total MTV was 34.3% and 69.9% respectively (p < 0.0001). Multivariate analysis revealed, besides IPI, that total MTV was independently predictive for PFS (HR: 2.31, 95% CI: 1.16 - 4.60, p = 0.0180) and OS (HR: 2.38, 95% CI: 1.12 - 5.04, p = 0.024). TLG and maximal SUV of tumor were not independent prognostic factors. CONCLUSIONS: An elevated total MTV was a predictor for shorter PFS and OS in patients with DLBCL receiving rituximab-containing therapy, independent of IPI.

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The purpose of this study was to determine the relevance of standardized uptake value (SUV) on [F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), focusing on tumor and bone marrow, to disease outcomes based on progression-free survival (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-containing chemotherapy.We reviewed the records of patients with DLBCL who were diagnosed between September 2009 and January 2013 and underwent pretreatment whole-body FDG PET/CT scans. All patients received rituximab-containing chemotherapy. The maximal SUV of tumor (SUVt) and maximal SUV of sternum (SUVst) were measured. Univariate and multivariate analyses were used to assess the prognostic significance of SUVt, SUVst, gender, age, clinical stage, international prognostic index (IPI), and laboratory tests.There were total 70 patients enrolled in this study. The median follow-up time was 36 months. An SUVt cut-off value of ≥19 had the best discriminative yield for PFS (P = .04). An SUVst cut-off value of ≥1.6 had the best discriminative yield for OS. The 3-year OS rates for patients with maximal SUVst < 1.6 and for those with maximal SUVst ≥1.6 were 74.8% and 57.1%, respectively (P = .04). Further forward, multivariate Cox proportional hazards model revealed that maximal SUVst (hazard ratio: 2.62; 95% confidence interval: 1.10-6.28; P = .03) and IPI were significant factors affecting OS.In patients with DLBCL receiving rituximab-containing chemotherapy, elevated maximal SUVt ≥19 was an independent predictor for shorter PFS, and maximal SUVst ≥1.6 was an independent predictor for shorter OS. It adds the value of pretreatment FDG PET/CT scans.

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