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Despite significant progress in combining cancer immunotherapy with chemotherapy to treat triple negative breast cancer (TNBC), challenges persist due to target depletion and tumor heterogeneity, especially in metastasis. Chemotherapy lacks precise targeting abilities, and targeted therapy is inadequate in addressing the diverse heterogeneity of tumors. To address these challenges, we introduce RGDEVD-DOX as a tumor-specific immunogenic agent, namely TPD1, which targets integrin αvß3 and gets continuously activated by apoptosis. TPD1 facilitates the caspase-3-mediated in situ amplification that results in tumor-specific accumulation of doxorubicin. This local concentration of doxorubicin induces immunogenic cell death and promotes the recruitment of immune cells to the tumor site. Notably, the tumor-targeting capabilities of TPD1 help bypass the systemic immunotoxicity of doxorubicin. Consequently, this alters the tumor microenvironment, converting it into a 'hot' tumor that is more susceptible to immune checkpoint inhibition. We demonstrated the anti-metastatic and anti-cancer efficacy of this treatment using various xenograft and metastatic models. This study underscores the high potential of caspase-3 cleavable peptide-drug conjugates to be used in conjunction with anti-cancer immunotherapies.
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BACKGROUND: Tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) and incorporation of 131I-metaiodobenzylguanidine (131I-MIBG) treatment have shown positive outcomes in high-risk neuroblastoma. However, more optimized treatment strategies are still needed. PROCEDURE: The NB-2014 study was a nonrandomized, prospective trial that examined survival outcomes in metastatic high-risk neuroblastoma patients using response-adapted consolidation therapy. We used post-induction residual 123I-MIBG status at metastatic sites as a treatment response marker. Patients achieving complete resolution of MIBG uptake at metastatic sites underwent a reduced first HDCT/auto-SCT with a 20% dose reduction in HDCT. After the first HDCT/auto-SCT, patients with remaining MIBG uptake received dose-escalated (18 mCi/kg) 131I-MIBG treatment. In contrast, those with complete resolution of MIBG at metastatic sites received a standard dose (12 mCi/kg) of 131I-MIBG. We compared survival and toxicity outcomes with a historical control group from the NB-2009. RESULTS: Of 65 patients treated, 63% achieved complete resolution of MIBG uptake at metastatic sites following induction chemotherapy, while 29% of patients still had MIBG uptake at metastatic sites after the first HDCT/auto-SCT. The 3-year event-free survival (EFS) and overall survival (OS) rates were 68.2% ± 6.0% and 86.5% ± 4.5%, respectively. Compared to NB-2009, EFS was similar (p = .855); however, NB-2014 had a higher OS (p = .031), a lower cumulative incidence of treatment-related mortality (p = .036), and fewer acute and late toxicities. CONCLUSIONS: Our results suggest that response-adaptive consolidation therapy based on chemotherapy response at metastatic sites facilitates better treatment tailoring, and appears promising for patients with metastatic high-risk neuroblastoma.
Subject(s)
3-Iodobenzylguanidine , Consolidation Chemotherapy , Neuroblastoma , Humans , Neuroblastoma/therapy , Neuroblastoma/mortality , Neuroblastoma/pathology , Neuroblastoma/drug therapy , Female , Male , Child, Preschool , Infant , Child , 3-Iodobenzylguanidine/therapeutic use , Prospective Studies , Survival Rate , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adolescent , Follow-Up Studies , Transplantation, Autologous , Prognosis , Hematopoietic Stem Cell Transplantation , RadiopharmaceuticalsABSTRACT
Perilunate fracture dislocations (PLFDs) are uncommon, usually resulting from high-energy trauma. Several classification systems describe the patterns of injury seen, but there is still significant variation and patterns of injury that do not fit within these classifications continue to be described. Carpal coalitions are rare, mostly asymptomatic, and are, as a result, usually identified incidentally. We describe the case of a transradial transcapitate PLFD in a patient with a Minnaar Type 3 lunotriquetral coalition. Radiographic, clinical, and patient-reported outcomes are reported. When presented with a rare anatomical variation in the context of a complex injury, the importance of managing these complex injuries according to principles is highlighted.
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BACKGROUND AND OBJECTIVES: The recent developments in chronic thromboembolic pulmonary hypertension (CTEPH) are emphasizing the multidisciplinary team. We report on the changes in clinical practice following the development of a multidisciplinary team, based on our 7 years of experience. METHODS: Multidisciplinary team was established in 2015 offering both balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) with technical upgrades by internal and external expertise. For operable cases, PEA was recommended as the primary treatment modality, followed by pulmonary angiography and right heart catheterization after 6 months to evaluate treatment effect and identify patients requiring further BPA. For patients with inoperable anatomy or high surgical risk, BPA was recommended as the initial treatment modality. Patient data and clinical outcomes were closely monitored. RESULTS: The number of CTEPH treatments rapidly increased and postoperative survival improved after team development. Before the team, 38 patients were treated by PEA for 18 years; however, 125 patients were treated by PEA or BPA after the team for 7 years. The number of PEA performed was 64 and that of BPA 342 sessions. World Health Organization functional class I or II was achieved in 93% of patients. The patients treated with PEA was younger, male dominant, higher pulmonary artery pressure, and smaller cardiac index, than BPA-only patients. In-hospital death after PEA was only 1 case and none after BPA. CONCLUSIONS: The balanced development of BPA and PEA through a multidisciplinary team approach proved synergistic in increasing the number of actively treated CTEPH patients and improving clinical outcomes.
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Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells in the small intestine, suppressed pathogenic type 2 immune responses, increased interferon-γ+ and interleukin-10+ regulatory T cell populations, and restored ileal abundances of Eggerthellaceae and Enterorhabdus in allergic mice. Overall, our findings underscore the therapeutic potential of the engineered allergen gel as a suitable microbiome-modulating platform for food allergy and other allergic diseases.
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KRAS-mutant cancers, due to their protein targeting complexity, present significant therapeutic hurdles. The identification of the macropinocytic phenotype in these cancers has emerged as a promising alternative therapeutic target. Our study introduces MPD1, an macropinocytosis-targeting peptide-drug conjugates (PDC), which is developed to treat KRAS mutant cancers. This PDC is specifically designed to trigger a positive feedback loop through its caspase-3 cleavable characteristic. However, we observe that this loop is hindered by DNA-PK mediated DNA damage repair processes in cancer cells. To counter this impediment, we employ AZD7648, a DNA-PK inhibitor. Interestingly, the combined treatment of MPD1 and AZD7648 resulted in a 100% complete response rate in KRAS-mutant xenograft model. We focus on the synergic mechanism of it. We discover that AZD7648 specifically enhances macropinocytosis in KRAS-mutant cancer cells. Further analysis uncovers a significant correlation between the increase in macropinocytosis and PI3K signaling, driven by AMPK pathways. Also, AZD7648 reinforces the positive feedback loop, leading to escalated apoptosis and enhanced payload accumulation within tumors. AZD7648 possesses broad applications in augmenting nano-sized drug delivery and preventing DNA repair resistance. The promising efficacy and evident synergy underscore the potential of combining MPD1 with AZD7648 as a strategy for treating KRAS-mutant cancers.
Subject(s)
Peptides , Pinocytosis , Protein Kinase Inhibitors , Proto-Oncogene Proteins p21(ras) , Pinocytosis/drug effects , Humans , Animals , Proto-Oncogene Proteins p21(ras)/genetics , Cell Line, Tumor , Peptides/pharmacology , Peptides/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/chemistry , DNA-Activated Protein Kinase/antagonists & inhibitors , DNA-Activated Protein Kinase/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Mutation , Mice, Nude , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Female , Mice , Xenograft Model Antitumor AssaysABSTRACT
Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of CDI between 2011 and 2019 after propensity score matching. We performed a regression analysis to compare the differences in the length of hospital stay and medical costs between patients with CDI and controls (gastroenteritis and colitis). The CDI hospitalization rate increased 2.9-fold between 2011 and 2019. The CDI group had higher comorbidity index scores and was more frequently diagnosed at tertiary hospitals and in the Seoul region than the control group (all p < 0.001). The annual incidence rate of CDI/10,000 persons significantly increased in both sexes and all age groups. The length of hospital stay and medical costs were 3.3-fold and 5.0-fold greater, respectively, in the CDI than in the control group (both p < 0.001). Although the length of hospital stay decreased, total medical costs increased in all age groups and both sexes between 2011 and 2019 (all p < 0.001). When compared with the control group, the CDI-attributable length of hospital stay and medical cost were greater by 15.3 days and KRW 3413 (×103), respectively, after matching. In conclusion, CDI incidence, particularly among the elderly population with comorbidities, has been increasing. In addition, the length of hospital stay and total medical costs of the CDI group were greater than those of the control group.
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While several studies have proposed a connection between the gut microbiome and the pathogenesis of Graves's disease (GD), there has been a lack of reports on alteration in microbiome following using anti-thyroid drug treatment (ATD) to treat GD. Stool samples were collected from newly diagnosed GD patients provided at baseline and after 6 months of ATD treatment. The analysis focused on investigating the association between the changes in the gut microbiome and parameter including thyroid function, thyroid-related antibodies, and the symptom used to assess hyperthyroidism before and after treatment. A healthy control (HC) group consisting of data from 230 healthy subjects (110 males and 120 females) sourced from the open EMBL Nucleotide Sequence Database was included. Twenty-nine GD patients (14 males and 15 females) were enrolled. The analysis revealed a significant reduction of alpha diversity in GD patients. However, after ATD treatment, alpha diversity exhibited a significant increase, restored to levels comparable to the HC levels. Additionally, GD patients displayed lower levels of Firmicutes and higher levels of Bacteroidota. Following treatment, there was an increased in Firmicutes and a decrease in Bacteroidota, resembling levels found in the HC levels. The symptoms of hyperthyroidism were negatively associated with Firmicutes and positively associated with Bacteroidota. GD had significantly lower levels of Roseburia, Lachnospiraceaea, Sutterella, Escherichia-shigella, Parasuterella, Akkermansia, and Phascolarctobacterium compared to HC (all p < 0.05). Post-treatment, Subdoligranulum increased (p = 0.010), while Veillonella and Christensenellaceaea R-7 group decreased (p = 0.023, p = 0.029, respectively). Anaerostipes showed a significant association with both higher smoking pack years and TSHR-Ab levels, with greater abundantce observed in smokers among GD (p = 0.16). Although reduced ratio of Firmicutes/Bacteroidetes was evident in GD, this ratio recovered after treatment. This study postulates the involvement of the gut microbiome in the pathogenesis of GD, suggesting potential restoration after treatment.
Subject(s)
Antithyroid Agents , Gastrointestinal Microbiome , Graves Disease , Humans , Graves Disease/drug therapy , Graves Disease/microbiology , Gastrointestinal Microbiome/drug effects , Male , Female , Adult , Antithyroid Agents/therapeutic use , Middle Aged , Feces/microbiology , Case-Control StudiesABSTRACT
We evaluated modulation of the immunosuppressive tumor microenvironment in both local and liver metastatic colorectal cancer (LMCC), focusing on tumor-associated macrophages, which are the predominant immunosuppressive cells in LMCC. We developed an orally administered metronomic chemotherapy regimen, oral CAPOX. This regimen combines capecitabine and a nano-micelle encapsulated, lysine-linked deoxycholate and oxaliplatin complex (OPt/LDC-NM). The treatment effectively modulated immune cells within the tumor microenvironment by activating the cGAS-STING pathway and inducing immunogenic cell death. This therapy modulated immune cells more effectively than did capecitabine monotherapy, the current standard maintenance chemotherapy for colorectal cancer. The macrophage-modifying effect of oral CAPOX was mediated via the cGAS-STING pathway. This is a newly identified mode of immune cell activation induced by metronomic chemotherapy. Moreover, oral CAPOX synergized with anti-PD-1 antibody (αPD-1) to enhance the T-cell-mediated antitumor immune response. In the CT26. CL25 subcutaneous model, combination therapy achieved a 91 % complete response rate with a confirmed memory effect against the tumor. This combination also altered the immunosuppressive tumor microenvironment in LMCC, which αPD-1 monotherapy could not achieve. Oral CAPOX and αPD-1 combination therapy outperformed the maximum tolerated dose for treating LMCC, suggesting metronomic therapy as a promising strategy.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Membrane Proteins , Nucleotidyltransferases , Oxaliplatin , Tumor Microenvironment , Tumor Microenvironment/drug effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Animals , Membrane Proteins/metabolism , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Oxaliplatin/administration & dosage , Liver Neoplasms/secondary , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/immunology , Administration, Oral , Cell Line, Tumor , Nucleotidyltransferases/metabolism , Mice , Mice, Inbred BALB C , Capecitabine/pharmacology , Capecitabine/therapeutic use , Capecitabine/administration & dosage , Humans , Signal Transduction/drug effects , Female , Deoxycholic Acid/chemistry , Deoxycholic Acid/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Tumor-Associated Macrophages/drug effects , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolismABSTRACT
Recent advancements in genomics, transcriptomics, and metabolomics have significantly advanced our understanding of the human gut microbiome and its impact on the efficacy and toxicity of anti-cancer therapeutics, including chemotherapy, immunotherapy, and radiotherapy. In particular, prebiotics, probiotics, and postbiotics are recognized for their unique properties in modulating the gut microbiota, maintaining the intestinal barrier, and regulating immune cells, thus emerging as new cancer treatment modalities. However, clinical translation of microbiome-based therapy is still in its early stages, facing challenges to overcome physicochemical and biological barriers of the gastrointestinal tract, enhance target-specific delivery, and improve drug bioavailability. This review aims to highlight the impact of prebiotics, probiotics, and postbiotics on the gut microbiome and their efficacy as cancer treatment modalities. Additionally, we summarize recent innovative engineering strategies designed to overcome challenges associated with oral administration of anti-cancer treatments. Moreover, we will explore the potential benefits of engineered gut microbiome-modulating approaches in ameliorating the side effects of immunotherapy and chemotherapy.
Subject(s)
Gastrointestinal Microbiome , Neoplasms , Prebiotics , Probiotics , Animals , Humans , Antineoplastic Agents/administration & dosage , Immunotherapy/methods , Neoplasms/drug therapy , Neoplasms/therapy , Prebiotics/administration & dosage , Probiotics/administration & dosageABSTRACT
Immune-cell-derived membranes have garnered significant attention as innovative delivery modalities in cancer immunotherapy for their intrinsic immune-modulating functionalities and superior biocompatibilities. Integrating additional parental cell membranes or synthetic lipid vesicles into cellular vesicles can further potentiate their capacities to perform combinatorial pharmacological activities in activating antitumor immunity, thus providing insights into the potential of hybrid cellular vesicles as versatile delivery vehicles for cancer immunotherapy. Here, we have developed a macrophage-membrane-derived hybrid vesicle that has the dual functions of transporting immunotherapeutic drugs and shaping the polarization of tumor-associated macrophages for cancer immunotherapy. The platform combines M1 macrophage-membrane-derived vesicles with CXCR4-binding-peptide-conjugated liposomes loaded with manganese and doxorubicin. The hybrid nanovesicles exhibited remarkable macrophage-targeting capacity through the CXCR4-binding peptide, resulting in enhanced macrophage polarization to the antitumoral M1 phenotype characterized by proinflammatory cytokine release. The manganese/doxorubicin-loaded hybrid vesicles in the CXCR4-expressing tumor cells evoked potent cancer cytotoxicity, immunogenic cell death of tumor cells, and STING activation. Moreover, cotreatment with manganese and doxorubicin promoted dendritic cell maturation, enabling effective tumor growth inhibition. In murine models of CT26 colon carcinoma and 4T1 breast cancer, intravenous administration of the manganese/doxorubicin-loaded hybrid vesicles elicited robust tumor-suppressing activity at a low dosage without adverse systemic effects. Local administration of hybrid nanovesicles also induced an abscessive effect in a bilateral 4T1 tumor model. This study demonstrates a promising biomimetic manganese/doxorubicin-based hybrid nanovesicle platform for effective cancer immunotherapy tailored to the tumor microenvironment, which may offer an innovative approach to combinatorial immunotherapy.
Subject(s)
Breast Neoplasms , Neoplasms , Humans , Animals , Mice , Female , Manganese/pharmacology , Biomimetics , Doxorubicin/therapeutic use , Macrophages/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Neoplasms/drug therapy , Neoplasms/metabolism , Immunotherapy/methods , Peptides/pharmacology , Tumor Microenvironment , Cell Line, Tumor , Receptors, CXCR4/metabolismABSTRACT
Colorectal cancer (CRC) ranks third in cancer incidence and stands as the second leading cause of cancer-related deaths globally. CRC tumorigenesis results from a cumulative set of genetic and epigenetic alterations, disrupting cancer-regulatory processes like cell proliferation, metabolism, angiogenesis, cell death, invasion, and metastasis. Key epigenetic modifications observed in cancers encompass abnormal DNA methylation, atypical histone modifications, and irregularities in noncoding RNAs, such as microRNAs and long noncoding RNAs. The advancement in genomic technologies has positioned these genetic and epigenetic shifts as potential clinical biomarkers for CRC patients. This review concisely covers the fundamental principles of CRC-associated epigenetic changes, and examines in detail their emerging role as biomarkers for early detection, prognosis, and treatment response prediction.
Subject(s)
Dupuytren Contracture , Humans , Dupuytren Contracture/surgery , Finger Joint/surgery , Fasciotomy , ExtremitiesABSTRACT
OBJECTIVES: Although several studies have shown the usefulness of artificial intelligence to identify abnormalities in small-bowel capsule endoscopy (SBCE) images, few studies have proven its actual clinical usefulness. Thus, the aim of this study was to examine whether meaningful findings could be obtained when negative SBCE videos were reanalyzed with a deep convolutional neural network (CNN) model. METHODS: Clinical data of patients who received SBCE for suspected small-bowel bleeding at two academic hospitals between February 2018 and July 2020 were retrospectively collected. All SBCE videos read as negative were reanalyzed with the CNN algorithm developed in our previous study. Meaningful findings such as angioectasias and ulcers were finally decided after reviewing CNN-selected images by two gastroenterologists. RESULTS: Among 202 SBCE videos, 103 (51.0%) were read as negative by humans. Meaningful findings were detected in 63 (61.2%) of these 103 videos after reanalyzing them with the CNN model. There were 79 red spots or angioectasias in 40 videos and 66 erosions or ulcers in 35 videos. After reanalysis, the diagnosis was changed for 10 (10.3%) patients who had initially negative SBCE results. During a mean follow-up of 16.5 months, rebleeding occurred in 19 (18.4%) patients. The rebleeding rate was 23.6% (13/55) for patients with meaningful findings and 16.1% (5/31) for patients without meaningful findings (P = 0.411). CONCLUSION: Our CNN algorithm detected meaningful findings in negative SBCE videos that were missed by humans. The use of deep CNN for SBCE image reading is expected to compensate for human error.
Subject(s)
Capsule Endoscopy , Deep Learning , Humans , Capsule Endoscopy/methods , Artificial Intelligence , Retrospective Studies , UlcerABSTRACT
Background/Aims: This study investigated whether the personality traits of endoscopists are associated with the effect of interventions for the improvement of colonoscopy quality. Methods: This prospective, multicenter, single-blind study was performed with 13 endoscopists in three health screening centers over a 12-month period. Quality indicators (QIs), including adenoma detection rate (ADR), polyp detection rate (PDR), and withdrawal time, were measured every 3 months. Consecutive interventions for the improvement of colonoscopy quality were conducted every 3 months, which included the personal notification of QIs, the in-group notification of QIs, and finally a targeted "quality education" session. The personality traits of each endoscopist were evaluated for perfectionism, fear of negative evaluation, and cognitive flexibility after the last QI assessment. Results: A total of 4,095 colonoscopies were evaluated to measure the QIs of the individual endoscopists for 12 months. The mean ADR, PDR, and withdrawal time of the 13 endoscopists were 32.3%, 47.7%, and 394 seconds at baseline and increased to 39.0%, 55.1%, and 430 seconds by the end of the study (p=0.003, p=0.006, and p=0.004, respectively). Among the three interventions, only quality education significantly improved QIs: ADR, 36.0% to 39.0% (odds ratio, 1.28; 95% confidence interval, 1.01 to 1.63). The improvement of ADR and PDR by education was significantly associated with perfectionism (r=0.617, p=0.033 and r=0.635, p=0.027, respectively) and fear of negative evaluation (r=0.704, p=0.011 and r=0.761, p=0.004, respectively). Conclusions: Education can improve colonoscopy quality, and its effect size is associated with an endoscopist's personal traits such as perfectionism and fear of negative evaluation (Clinical-Trials.gov Registry NCT03796169).
Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Humans , Colonic Polyps/diagnosis , Prospective Studies , Single-Blind Method , Colonoscopy , Adenoma/diagnosis , Personality , Colorectal Neoplasms/diagnosis , Early Detection of CancerABSTRACT
Background: Total metabolic tumor volume (TMTV) in 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) predicts patient outcome in follicular lymphoma (FL); however, it requires laborious segmentation of all lesions. We investigated the prognostic value of the metabolic bulk volume (MBV) obtained from the single largest lesion. Methods: Pretreatment FDG PET/computed tomography (CT) scans of 201 patients were analyzed for TMTV and MBV using a 41% maximum standardized uptake value (SUVmax) threshold. Results: During a median follow-up of 3.2 years, 54 events, including 14 deaths, occurred. Optimal cut-offs were 121.1 cm3 for TMTV and 24.8 cm3 for MBV. Univariable predictors of progression-free survival (PFS) included a high Follicular Lymphoma International Prognostic Index 2 (FLIPI2) score, TMTV, and MBV. In the multivariable analysis, high TMTV and MBV were independent predictors of worse PFS (P =0.015 and 0.033). Furthermore, in a sub-group with FLIP2 scores of 0-2 (n = 132), high MBV could identify patients with worse PFS (P = 0.007). . Conclusion: Readily measurable MBV is useful for stratifying risk in FL patients.
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BACKGROUND: F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is useful in multiple myeloma (MM) for initial workup and treatment response evaluation. Herein, we evaluated the prognostic value of semi-quantitative FDG parameters for predicting the overall survival (OS) of MM patients with or without autologous stem cell transplantation (ASCT). METHODS: Study subjects comprised 227 MM patients who underwent baseline FDG PET/CT. Therein, 123 underwent ASCT while 104 did not. Volumes of interest (VOIs) of bones were drawn on CT images using a threshold of 150 Hounsfield units. FDG parameters of maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and number of focal lesions (FLs) were measured. Kaplan-Meier survival analysis with log-rank tests and Cox proportional hazards regression analyses were performed for overall survival (OS). RESULTS: In the ASCT cohort, R-ISS stage, MTV, and TLG were associated with survival. In the non-ASCT cohort, however, R-ISS stage was not associated with patient outcomes. In contrast, high SUVmax, SUVmean, MTV, TLG, and FL could predict worse OS (hazard ratio [HR] = 2.569, 2.649, 2.506, 2.839, and 1.988, respectively). Importantly, combining FDG parameters with R-ISS stage provided a new risk classification system that discriminated worse OS in the non-ASCT cohort significantly better than did R-ISS stage alone. CONCLUSIONS: In the non-ASCT cohort, semi-quantitative FDG parameters were significant predictors of worse OS. Furthermore, combining FDG parameters with R-ISS stage may provide a new risk staging system that can better stratify the survival of MM patients without ASCT.
Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Fluorodeoxyglucose F18/metabolism , Positron Emission Tomography Computed Tomography , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/therapy , Transplantation, Autologous , Prognosis , Retrospective Studies , Tumor Burden , RadiopharmaceuticalsABSTRACT
BACKGROUD/AIMS: Several bowel preparation scales have been developed, but they are variably validated to guide clinical practice. The aim of this study was to assess the interobserver reliability between internal and external endoscopists using the Harefield Cleaning Scale (HCS). METHODS: Data was collected from a study evaluating the efficacy of oral sulfate tablets in patients undergoing colonoscopy. The assessments of bowel cleansing were carried out by four internal endoscopists at the time of the procedure, and colonoscopy video recordings were reviewed independently by three external endoscopists. Interobserver reliability was quantified using Cohen's Kappa coefficient, and scores and grades of each segment were compared between internal and external endoscopist groups. RESULTS: Among 83 colonoscopy videos, interobserver reliability yielded a fair agreement between internal and external endoscopists, with a Cohen's Kappa coefficient of 0.39 (95% CI 0.08-0.70). Successful overall preparation rates (100% vs 98.8%) and high-quality preparation rates (88% vs 94%) were excellent and comparable between the two groups. In contrast, one case of unsuccessful cleansing (grade C) was documented, only in the external group. In addition, the interobserver reliability between internal and external endoscopists comparing each segmental score yielded a slight agreement in the descending colon (0.11, 95% CI - 0.02 to 0.23) and sigmoid colon (0.04, 95% CI - 0.18 to 0.26). DISCUSSION: Interobserver reliability between internal and external endoscopists using the HCS was fair. However, the HCS may be limited as a reliable scale for assessing bowel preparation quality in the left colon, where liquid is mainly retained in the left lateral position.
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BACKGROUND: Recently, swallowing resistive exercise using kinesiology taping (KT) has been reported as a novel method for dysphagia rehabilitation However, clinical evidence is still unclear, and effects in the elderly have not been confirmed. OBJECTIVE: This study aimed to investigate the effects of suprahyoid muscle strengthening exercise using KT on muscle activation and thickness in community-dwelling elderly. METHODS: A total of 24 healthy older people were enrolled in this study and randomly assigned to an experimental group and a placebo group. In the experimental group, KT was attached to the front of the neck with a tension of about 70% to 80%, and a resistive swallowing exercise was performed. In the placebo group, the tape was applied similarly but without tension. Both groups performed resistive swallowing exercises 10 times a day (50 swallows per day) for 6 weeks. The activation and thickness of the suprahyoid muscles were measured using portable ultrasound equipment and an surface electromyelograph device. RESULTS: The experimental group showed a significant increase in suprahyoid muscle activation (mean and peak) and muscle thickness (digastric and mylohyoid) than the placebo group (all, P < .05). CONCLUSION: This study confirmed that suprahyoid muscle strengthening exercise using KT had a positive effect on the suprahyoid muscles in healthy older adults, thus suggesting the possibility of a therapeutic exercise method for dysphagia rehabilitation.