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Objectives: For early gastrointestinal lesions, size is an important factor in the selection of treatment. Virtual scale endoscope (VSE) is a newly developed endoscope that can measure size more accurately than visual measurement. This study aimed to investigate whether VSE measurement is accurate for early gastrointestinal lesions of various sizes and morphologies. Methods: This study prospectively enrolled patients with early gastrointestinal lesions ≤20 mm in size visually. Lesion sizes were measured in the gastrointestinal tract visually, on endoscopic resection specimens with VSE, and finally on endoscopic resection specimens using a ruler. The primary endpoint was the normalized difference (ND) of VSE measurement. The secondary endpoints were the ND of visual measurement and the variation between NDs of VSE and visual measurements. ND was calculated as (100 × [measured size - true size] / true size) (%). True size was defined as size measured using a ruler. Results: This study included 60 lesions from April 2022 to December 2022, with 20 each in the esophagus, stomach, and colon. The lesion size was 14.0 ± 6.3 mm (mean ± standard deviation). Morphologies were protruded, slightly elevated, and flat or slightly depressed type in 8, 24, and 28 lesions, respectively. The primary endpoint was 0.3 ± 8.8%. In the secondary endpoints, the ND of visual measurement was -1.7 ± 29.3%, and the variability was significantly smaller in the ND of VSE measurement than in that of visual measurement (p < 0.001, F-test). Conclusions: VSE measurement is accurate for early gastrointestinal lesions of various sizes and morphologies.
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BACKGROUND: Although concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard treatment for patients with stage III non-small cell lung cancer (NSCLC), only half of the patients are allowed to receive CCRT in real-world settings. We evaluated the efficacy and safety of durvalumab after radiation monotherapy for NSCLC patients who are ineligible for chemoradiotherapy. METHODS: A single-arm, prospective, open-label, multicenter phase II trial was conducted in Japan. The patients received radiation (54-66 Gy) followed by durvalumab (10 mg/kg every 2 weeks for up to 12 months). The primary endpoint was the 1-year progression-free survival (PFS) rate. The secondary endpoints were the objective response rate (ORR), PFS, overall survival (OS), and safety. RESULTS: Between September 2019 and April 2021, 33 patients were enroled from eight institutions. The median patient age was 79 years, and the majority of patients were male (78.8%). The 1-year PFS rate was 39.1% (90% confidence interval [CI]: 24.7-54.6%). Three patients (9.1%) had a performance status of 2. The ORR was 42.4% (95% CI: 27.2-59.2%). The median PFS and OS were 8.9 (95% CI: 7.4-19.4) and 20.8 (95% CI: 15.8-not estimable) months, respectively. The most common adverse event was radiation pneumonitis (51.5%). The median treatment duration was 6.4 (range: 0.50-12.0) months for durvalumab. At the endpoint, 30.3% (10/33) of the patients had completed 1 year of durvalumab therapy. CONCLUSIONS: Durvalumab is an effective treatment with tolerable toxicity following radiation monotherapy in stage III NSCLC patients who are ineligible for chemoradiotherapy. TRIAL REGISTRATION: JMA-IIA00434 (jRCT).
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Female , Humans , Male , Carcinoma, Non-Small-Cell Lung/drug therapy , Chemoradiotherapy , Lung Neoplasms/drug therapy , Neoplasm Staging , Prospective StudiesABSTRACT
Background: The combination of erlotinib, a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and ramucirumab, an anti-vascular endothelial growth factor receptor (VEGFR) antibody, is one of the most effective treatments for patients with non-small cell lung cancer (NSCLC) and EGFR mutation. However, little is known about the safety and efficacy of this combination treatment for patients with brain metastases. Methods: This single arm, prospective, open-label, multicenter, phase II study will recruit 32 NSCLC patients with EGFR mutation (except for T790M mutation) and brain metastases (asymptomatic or mild symptoms). Patients will be treated with erlotinib at a dose of 150 mg/body once daily and ramucirumab at a dose of 10 mg/kg once every 2 weeks. The primary endpoint is intracranial overall response rate (iORR) and the secondary endpoints are intracranial disease control rate, intracranial progression-free survival (iPFS), extracranial ORR, extracranial PFS, ORR, overall PFS, overall survival (OS), and safety. The planned number of enrollments was calculated based on a one-sample binomial test (normal approximation) with a two-sided α level of 5% and 80% power, assuming that the expected iORR is 65% and the iORR threshold is 40%. Discussion: A prospective study to confirm the safety and efficacy of the combined erlotinib plus ramucirumab treatment for NSCLC patients with EGFR mutation and brain metastases is ongoing. Trial Registration: Japan Registry of Clinical Trials, jRCTs051220059.
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BACKGROUND: Sepsis occurs as a result of dysregulated host response to infection. However, cytokine adsorption therapy may restore the balance of proinflammatory and anti-inflammatory mediator responses in patients with sepsis. This study aimed to determine the cytokine adsorption ability of two different types of continuous renal replacement therapy (CRRT) hemofilters for polyethyleneimine-coated polyacrylonitrile (AN69ST) (surface-treated) and polymethylmethacrylate (PMMA) CRRT. METHODS: We performed a randomized controlled trial among sepsis patients undergoing CRRT, who were randomly assigned (1:1) to receive either AN69ST or PMMA-CRRT. The primary outcome was cytokine clearance of hemofilter adsorption (CHA). The secondary endpoints were the intensive care unit (ICU) and 28-day mortalities. RESULTS: We randomly selected 52 patients. Primary outcome data were available for 26 patients each in the AN69ST-CRRT and PMMA-CRRT arms. The CHA of high-mobility group box 1, tumor necrosis factor, interleukin (IL)-8, monokine induced by interferon-γ, and macrophage inflammatory protein were significantly higher in the AN69ST-CRRT group than in the PMMA-CRRT group (P < 0.001, P < 0.01, P < 0.001, P < 0.001 and P < 0.001, respectively). In contrast, the CHA of IL-6 was significantly higher in the PMMA-CRRT group than in the AN69ST-CRRT group (P < 0.001). In addition, the 28-day mortality was not significantly different between the two groups (50% in AN69ST-CRRT vs. 30.8% in PMMA-CRRT, P = 0.26). CONCLUSION: AN69ST and PMMA membranes have different cytokine CHA in patients with sepsis. Therefore, these two hemofilters may have to be used depending on the target cytokine. TRIAL REGISTRATION NUMBER: This study was registered in the University Hospital Medical Information Network on November 1, 2017 (Trial No: UMIN000029450, https://center6.umin.ac.jp ).
Subject(s)
Continuous Renal Replacement Therapy , Humans , Cytokines , Polymethyl Methacrylate , Polyethyleneimine , AdsorptionABSTRACT
BACKGROUND: Dacomitinib significantly improves progression-free survival and overall survival (OS) compared with gefitinib in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib. METHODS: We performed a single-arm, prospective, open-label, multi-institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR-activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks. RESULTS: In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32-83 years), 20 were male, and 36 had a performance status of 0-1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%-56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression-free survival was 6.8 months (95% CI, 4.0-8.6 months) and median OS was 21.6 months (95% CI, 17.0 months-not reached). CONCLUSION: Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Male , Aged , Female , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Prospective Studies , Protein Kinase Inhibitors/therapeutic use , ErbB Receptors/genetics , MutationABSTRACT
The virtual scale endoscope (VSE) is a new endoscope that helps estimate the size of neoplasms in the gastrointestinal tract. We compared the accuracy of polyp size estimation by VSE with that of visual estimation. A dual center prospective study was conducted in two Japanese academic endoscopy units. Ten endoscopists (five trainees and five experts) estimated the size of 20 simulated polyps in four colon phantoms during colonoscopy by two methods: conventional visual estimation and estimation by VSE. The primary endpoint was the relative accuracy in relation to true polyp size according to visual estimation and VSE estimation during colonoscopy. The secondary endpoint was the required time (the time needed to measure in each procedure). The mean values of the primary end-point were 62.5% for visual estimation and 84.0% for VSE estimation; hence the result differed significantly (95% confidence interval 18.3-24.7; P < 0.001). The mean of required times was significantly longer for estimation by VSE (6.4 min) than that by visual estimation (2.9 min; P < 0.001). The accuracy of colorectal polyp size estimation was superior with VSE than with visual estimation during colonoscopy. In the future, VSE should be evaluated in actual clinical settings, including the time required for size estimation.
Subject(s)
Colonic Polyps , Colorectal Neoplasms , Humans , Colonic Polyps/diagnosis , Prospective Studies , Colonoscopy/methods , Colon , Colorectal Neoplasms/diagnosisABSTRACT
We conducted a multicenter prospective study on whether a comprehensive geriatric assessment (CGA) can predict the adverse events (AEs) of chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Patients aged ≥ 65 years with newly diagnosed DLBCL underwent a pretreatment baseline CGA consisting of six assessment tools: activities of daily living (ADL), instrumental ADL (IADL), mood, nutritional status, comorbidities, and cognitive function. An attending physician chose each patient's treatment but was blind to CGA results. Patients were grouped as "dependent" or "independent" according to the CGA. The primary endpoint was to evaluate the association between chemotherapy-induced grade 3-4 toxicity and CGA. Of 86 patients, 78 completed the designated CGA. The median age was 79 years (65-89). Seventy-two patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP-like) regimen, and six were treated with low-toxicity regimens. Forty-one patients were classified as dependent and 37 as independent. In multivariate analysis, an impairment of IADL was independently associated with grade 3-4 leukopenia (odds ratio [OR] 0.63; 95% confidence interval [CI] 0.43-0.92, p = 0.017) and anemia (OR 0.67; 95% CI 0.50-0.90, p = 0.008). The presence of a comorbidity was also associated with grade 3-4 non-hematological toxicity (OR 2.17; 95% CI 1.37-3.43, p = 0.001). The 4-year survival rate tended to be longer in the independent (72.7%) compared to dependent (56.9%) group. Overall, a CGA may be a useful tool for predicting serious AEs associated with chemotherapy in elderly patients with DLBCL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug-Related Side Effects and Adverse Reactions/prevention & control , Geriatric Assessment/methods , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Comorbidity , Drug Therapy , Female , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Prognosis , Prospective Studies , Treatment OutcomeABSTRACT
The standard of care for advanced non-small cell lung cancer (NSCLC) without known driver oncogenes is immune checkpoint inhibitor (ICI) therapy combined with platinum-based chemotherapy. About 20% of patients with advanced NSCLC have brain metastases, which are related to poor prognosis. However, the effect of ICI therapy combined with platinum-based chemotherapy on untreated brain metastases derived from NSCLC remains unclear. The primary endpoint of this study is intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥5 mm as target lesions. Eligible patients are 20 years of age or older with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥5 mm in size that has not been previously treated. Patients receive nivolumab plus ipilimumab intravenously combined with histology-based platinum doublet chemotherapy (two cycles). Individuals with known genetic driver alterations such as those affecting EGFR or ALK are excluded. Planned enrollment is 30 patients over 2.5 years at 27 oncology facilities in Japan. This is the first prospective study to focus on the intracranial response to ICI therapy combined with platinum-based chemotherapy in patients with untreated brain metastases derived from NSCLC. If the study demonstrates intracranial efficacy for this patient population, then this regimen has the potential to become a new treatment option for such individuals.
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BACKGROUND: In the PACIFIC study, progression-free survival (PFS) and overall survival (OS) of patients with unresectable, locally advanced, stage III non-small cell lung cancer (NSCLC) were prolonged by durvalumab as maintenance therapy after radical concurrent chemoradiotherapy using platinum-based antitumor agents. However, no data were obtained to reveal the efficacy of durvalumab after radiation monotherapy in patients unsuitable for chemoradiotherapy. Here, we describe an ongoing single-arm, prospective, open-label, multicenter phase II trial of durvalumab in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy (SPIRAL-RT study). METHODS: Durvalumab at 10 mg/kg body weight is administered every 2 weeks after radiation therapy until individual patients meet the discontinuation criteria. The treatment duration is up to 12 months. The primary endpoint is the 1-year PFS rate. Secondary endpoints are response rate, PFS, OS, and safety. Durvalumab treatment after radiation monotherapy is expected to prolong 1-year PFS rate and have acceptable adverse events. DISCUSSION: We are conducting an intervention study to investigate the safety and efficacy of durvalumab treatment in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy.
ABSTRACT
Capecitabine is selectively converted from 5'-DFUR to 5-fluorouracil (5-FU) in tumours by thymidine phosphorylase (TP). We investigated the addition of 5-nitrouracil (5-NU), a TP inhibitor, into blood samples for precise measurements of plasma 5-FU concentrations. The plasma concentration of 5-FU was measured after capecitabine administration. Two samples were obtained at 1 or 2 h after capecitabine administration and 5-NU was added to one of each pair. Samples were stored at room temperature or 4 °C and 5-FU concentrations were measured immediately or 1.5 or 3 h later. The mean plasma 5-FU concentration was significantly higher at room temperature than at 4 °C (p < 0.001). The 5-FU concentration was significantly increased in the absence of 5-NU than in the presence of 5-NU (p < 0.001). The 5-FU change in concentration was greater in the absence of 5-NU, and reached 190% of the maximum compared with baseline. A significant interaction was found between temperature and 5-NU conditions (p < 0.001). Differences between the presence or absence of 5-NU were greater at room temperature than under refrigerated conditions. 5-FU plasma concentrations after capecitabine administration varied with time, temperature, and the presence or absence of 5-NU. This indicates that plasma concentrations of 5-FU change dependent on storage conditions after blood collection.
Subject(s)
Antimetabolites, Antineoplastic/blood , Capecitabine/blood , Colorectal Neoplasms/drug therapy , Fluorouracil/blood , Thymidine Phosphorylase/antagonists & inhibitors , Uracil/analogs & derivatives , Adult , Antimetabolites, Antineoplastic/pharmacokinetics , Antimetabolites, Antineoplastic/pharmacology , Biotransformation , Capecitabine/pharmacokinetics , Capecitabine/pharmacology , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Female , Humans , Liver/metabolism , Male , Temperature , Thymidine Phosphorylase/metabolism , Time Factors , Uracil/pharmacologyABSTRACT
BACKGROUND: Dacomitinib is the first second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) to significantly improve overall survival in the patients of EGFR mutation-positive inoperable or postoperative recurrent non-small cell lung cancer (NSCLC). However, dermatologic adverse events (AEs) increase with dacomitinib treatment, and the management strategy for dermatologic AEs is crucial. In particular, a proactive strategy has become desirable in clinical practice settings. We designed a trial to assess a proactive strategy for dermatologic AEs associated with dacomitinib treatment. METHODS: This is a single-arm, prospective, open-label, multicenter, phase II trial. Patients with advanced NSCLC harboring EGFR-activating mutations will receive dacomitinib and prophylactic treatment as follows: minocycline, skin moisturizer, topical steroid, and sunscreen. Treatment will be continued until progressive disease or any of the discontinuation criteria are met. The primary endpoint is the incidence of dermatologic AEs (≥ grade 2) in the first 8 weeks of dacomitinib treatment. Secondary endpoints are the proportion of dose reduction of dacomitinib, progression-free survival, and safety. DISCUSSION: We are conducting a phase II study to explore the preventive efficacy of prophylactic medication against dacomitinib-induced dermatologic AEs. TRIAL REGISTRATION: jRCTs071190015.
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While it is important to treat lifestyle-related diseases for the primary and secondary prevention of cardiovascular diseases, medication adherence is still poor. Although various causes of poor adherence have been reported, the differences between physicians and their patients regarding the recognition of medication adherence have not been well-investigated.We administered a questionnaire about medication adherence to 300 outpatients and their 23 cardiologists at the Department of Cardiology, Fukuoka University Hospital. The questionnaires for patients and physicians included acceptable total number of drug doses and dosing schedule, forgetting to take the medicine, and dose-reduction or -increase based on self-judgement. The patients were 70.6â±â12.3 years old and 61.0% (nâ=â183) were male. Patients reported that it was acceptable to receive 0-5 doses twice daily. The patients were divided into two groups: an agreement group, in which physicians and their patients had the same answer to the question regarding forgetting medication (203 cases; 67.7%), and a disagreement group (97 cases; 32.3%). Overall, the inter-rater agreement between physicians and patients with regard to forgetting medication was significant, but slight (κ coefficientâ=â0.12). In a multivariate analysis, absence of hypertension [odds ratio (OR): 0.21, 95% confidence interval (CI): 0.09-0.50, Pâ<â.001), ß-blocker usage (OR: 1.86, 95% CI: 1.11-3.12, Pâ=â.02), and biguanide usage (OR: 4.04, 95% CI: 1.43-11.41, Pâ=â.01) were independent predictors of disagreement with regard to forgetting medication.The inter-rater agreement between physicians and patients with regard to medication adherence was slight. An increase in inter-rater agreement should improve medication adherence.
Subject(s)
Cardiovascular Diseases/drug therapy , Hypertension/drug therapy , Medication Adherence/statistics & numerical data , Physician-Patient Relations/ethics , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/psychology , Female , Humans , Hypertension/psychology , Japan/epidemiology , Life Style , Male , Medication Adherence/psychology , Patient Acceptance of Health Care/statistics & numerical data , Secondary Prevention , Self Report/statistics & numerical data , Surveys and QuestionnairesABSTRACT
BACKGROUND: Physicians have few opportunities to perform surgical lung biopsy (SLB) to diagnose idiopathic pleuroparenchymal fibroelastosis (IPPFE). Therefore, diagnostic criteria for IPPFE that do not require SLB must be established. Herein, we propose diagnostic criteria for IPPFE with and without SLB. METHODS AND RESULTS: The diagnostic criteria for IPPFE with SLB are histological, based on computed tomography (CT) lesions compatible with PPFE, predominantly in the upper lobes. The three diagnostic criteria for IPPFE without SLB are as follows: (1) radiologically possible IPPFE (a radiological criterion confirming CT lesions in both lung apexes, regardless of the lower lobe lesions); (2) radiologically probable IPPFE (also a radiological criterion, but mandatory to confirm chest radiograph findings of bilateral upward shift of the hilar structures and/or CT findings of volume loss of the upper lobes); (3) radiologically and physiologically probable IPPFE. Our data from 41 patients with IPPFE and 97 with idiopathic pulmonary fibrosis (IPF) showed that the percentage of the predicted values of the ratio of residual volume to total lung capacity (RV/TLC %pred.) ≥115% and body mass index (BMI) ≤20â¯kg/m2 plus RV/TLC %pred. ≥80% performed well for discriminating IPPFE from IPF. These parameters were thus added to criterion (3). CONCLUSIONS: We have proposed diagnostic criteria for IPPFE in patients with and without SLB. Both imaging criteria and physiological criteria using RV/TLC and BMI successfully discriminate IPPFE from chronic IIPs when SLB cannot be performed.
Subject(s)
Elastic Tissue , Lung Diseases, Interstitial/diagnosis , Parenchymal Tissue , Pleural Diseases/diagnosis , Body Mass Index , Diagnosis, Differential , Elastic Tissue/pathology , Fibrosis , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Lung Diseases, Interstitial/pathology , Pleural Diseases/pathology , Radiography, Thoracic , Residual Volume , Tomography, X-Ray Computed , Total Lung CapacityABSTRACT
Oxaliplatin is a key chemotherapy drug in patients with colorectal cancer. Administration of oxaliplatin via a peripheral vein often causes vascular pain. However, no studies have evaluated vascular pain in patients with colorectal cancer in relation to peripheral venous administration of chemotherapy with or without oxaliplatin. We evaluated oxaliplatin-induced vascular pain using subjective and objective methods. We determined if oxaliplatin induced vascular pain in patients with colorectal cancer using a Visual Analog Scale (VAS) and a PainVision PS-2100 device. We compared VAS score between chemotherapy regimens with or without oxaliplatin, and between genders. We also examined the correlations of VAS score with pain intensity examined by the PainVision PS-2100, and with age and vessel diameter. A total of 98 patients with colorectal cancer were enrolled in this study, including 78 patients who received oxaliplatin via peripheral venous administration and 20 who received chemotherapy without oxaliplatin. The median VAS scores in patients with and without oxaliplatin were 36.5 (interquartile range 9.0-60.0) and 0 (0-4.0), respectively (P < 0.001), and the median pain intensities according to PainVision were 43.5 (14.3-98) and 36.5 (9.3-58.5), respectively (P < 0.001). There was a positive correlation between VAS and pain intensity (r = 0.584), but no correlation between VAS score and age (r = -0.174) or vessel diameter (r = -0.107). Peripheral venous administration of oxaliplatin induced vascular pain, measured both subjectively and objectively, in patients with colorectal cancer, regardless of vessel diameter.
Subject(s)
Oxaliplatin/adverse effects , Pain/chemically induced , Vascular Diseases/chemically induced , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/drug therapy , Female , Humans , Male , Middle Aged , Oxaliplatin/therapeutic use , Phlebotomy/adverse effects , Sex FactorsABSTRACT
Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is rare and offers a poor prognosis; more accurate prognostic biomarkers are required. Our laboratory recently demonstrated that tumor budding, characterized by tumor cell clusters (< 5 cells), and laminin 5-γ2 staining of SCC of the EAC are associated with shorter survival. However, clusters composed of ≥ 5 tumor cells are also found in the stroma. Previous reports of colorectal cancer suggest that poorly differentiated clusters (PDCs) are a negative prognostic indicator. Here, we report on the association between PDCs and prognosis in SCC of the EAC. PDCs and tumor budding were histopathologically and immunohistochemically (cytokeratin AE1/AE3) analyzed in 31 cases of pre-treatment biopsy SCC of the EAC. Clusters in the stroma composed of < or ≥ 5 cancer cells were defined as tumor budding or PDCs, respectively. Entire tumors were initially scanned to identify greatest PDC density. Tumors with low or high PDC density were classified as low- and high-grade, respectively. Patients with high-grade PDCs had a significantly poorer outcome than those with low-grade. Even in cases of low-grade tumor budding, those with high-grade PDCs had a poor prognosis. Multivariate analysis results indicated that high-grade PDCs were associated with poor prognosis. PDC grade can provide a more accurate prognosis than tumor budding in SCC of the EAC.
Subject(s)
Ear Canal/pathology , Ear Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck/pathology , Adult , Aged , Aged, 80 and over , Ear Neoplasms/mortality , Female , Humans , Male , Middle Aged , Neoplasm Grading/methods , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/mortalityABSTRACT
BACKGROUND: Levels of the biomarkers presepsin and procalcitonin are affected by renal function. We evaluated the accuracies of presepsin and procalcitonin levels for diagnosing sepsis in patients with and without acute kidney injury (AKI). METHODS: We evaluated patients with presepsin and procalcitonin data, and classified them into AKI and non-AKI groups based on the Kidney Disease Improving Global Outcomes criteria. Each group was then subdivided according to sepsis status for each stage of AKI. Receiver operating characteristic curve analyses were used to investigate the accuracies of biomarker levels for diagnosing sepsis. RESULTS: In the non-AKI group, the area under the curves (AUCs) for procalcitonin and presepsin levels were 0.897 and 0.880, respectively (pâ¯=â¯.525) and optimal cut-off values were 0.10â¯ng/ml (sensitivity: 85.1%, specificity: 79.1%) and 240â¯pg/ml (sensitivity: 80.9%, specificity: 83.2%), respectively. In the stage 3 subgroup, the AUC for procalcitonin (0.946) was significantly higher than that for presepsin (0.768, pâ¯<â¯.001). The optimal cut-off values for diagnosing sepsis were 4.07â¯ng/ml (sensitivity: 87.2%, specificity: 93.5%) for procalcitonin and 500â¯pg/ml (sensitivity: 89.7%, specificity: 59.7%) for presepsin. CONCLUSIONS: In patients with severe AKI, the accuracy of the diagnosis of sepsis with procalcitonin was significantly higher than with presepsin.
Subject(s)
Acute Kidney Injury/complications , Limit of Detection , Lipopolysaccharide Receptors/metabolism , Peptide Fragments/metabolism , Procalcitonin/metabolism , Sepsis/diagnosis , Sepsis/metabolism , Aged , Female , Humans , Male , Middle Aged , Sepsis/complicationsABSTRACT
INTRODUCTION: Two opening methods are used for injection needle products: the "peel-apart method" where the adhesive surface of the packaging mount is peeled off, and the "push-off top method," where the needle hub is pressed against the mount to break it. However, the risks of bacterial contamination as a result of opening method remain unknown. The aim of our study was to evaluate the bacterial contamination of needle hubs upon the opening of injection needles by the peel-apart or push-off top method under various conditions. METHODS: Bacterial contamination upon the opening of injection needles was examined in two materials, paper and plastic. Various concentrations of Staphylococcus aureus were applied to the mount and were maintained under wet or dry conditions. Injection needles were opened using the peel-apart or push-off top method. Needle hub contamination was examined using agar medium colony counting. Clinically assumed conditions (the hands and saliva of anesthesiologists) were also evaluated. Data were statistically examined using the Cochran-Mantel-Haenszel, Jonckheere, and Fisher's exact tests. RESULTS: The lateral surfaces of needle hubs were contaminated using the push-off top method, but not by the peel-apart method, in a manner that was dependent on S. aureus concentrations. No significant differences were observed between mount materials. Needle hub contamination was significantly more severe for the wet than for the dry opening portion. The clinically assumed condition study revealed that the lateral and bottom surfaces of the needle hub were contaminated significantly more in the saliva contamination group than in the dry and wet hand groups. CONCLUSIONS: The bacterial contamination of needle hubs may occur upon the opening of injection needles when the push-off top method is used and may be affected by hands contaminated with saliva under clinical conditions.
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Since the effect of a percutaneous absorption-type dopamine agonist (DA) preparation, rotigotine patch, stably persists by once-a-day application, this dosage form is appropriate for Parkinson's disease patients showing levodopa induced wearing off phenomenon. On the other hand, skin disorders, mainly application site reaction, are characteristic problems associated with use of the patch. In this study, to clarify the influence of a topical agent used to prevent or treat rotigotine patch-induced skin disorder on continuation of the patch application, patients who started rotigotine patch application at our hospital were retrospectively surveyed. The one-year continuation rate of rotigotine patch application was 37.3% (53 of 142 cases). It was insufficient to prevent skin disorders, only by the pre-treatment of a moisturizing agent alone. Regarding the effective rate of topical agents used to treat skin disorders, that of very strong-class steroids was 89.5%, being significantly higher than those of weak steroids, moisturizing agents, and antihistamines. It was suggested that for countermeasures against rotigotine patch-induced skin disorders, treatment with very strong-class steroids for external use early after development of skin disorders is more effective than preventive treatment with topical agents regardless of the type. (Received March 30, 2017; Accepted May 16, 2017; Published September 1, 2017).
Subject(s)
Dopamine Agonists/adverse effects , Skin Diseases/chemically induced , Tetrahydronaphthalenes/adverse effects , Thiophenes/adverse effects , Adult , Aged , Aged, 80 and over , Dopamine Agonists/administration & dosage , Female , Humans , Male , Middle Aged , Retrospective Studies , Tetrahydronaphthalenes/administration & dosage , Thiophenes/administration & dosage , Transdermal PatchABSTRACT
BACKGROUND: The purpose of this study was to investigate whether polymyxin B hemoperfusion (PMX-HP) improves the survival of patients with septic shock. METHODS: This was a retrospective, multicenter study conducted on patients treated during a 3-year period. We performed propensity-score analyses of the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study database. The study included data on 1723 patients with septic shock aged 16 years or older. Furthermore, we divided patients into to PMX-HP- and non-PMX-HP-treated groups. The primary endpoint was all-cause hospital mortality; secondary endpoints included intensive care unit (ICU) mortality and number of ICU-free days (ICUFDs) in the first 28 days. RESULTS: Of 1,723 eligible patients, 522 had received PMX-HP. Propensity score matching created 262 matched pairs (i.e., 262 patients in each of the non-PMX-HP and PMX-HP groups). The proportion of all-cause hospital mortality was significantly lower in the PMX-HP group than in the non-PMX-HP group (32.8% vs. 41.2%; odds ratio (OR): 0.681; 95% confidence interval (CI): 0.470-0.987; P = 0.042). The number of ICUFD in the first 28 days was significantly higher in the PMX-HP group than in the non-PMX-HP group (18 (0-22) vs. 14 (0-22) days, respectively; P = 0.045). On the other hand, there was no significant difference in ICU mortality between the two groups (21.8% vs. 24.4%; OR: 0.844; CI: 0.548-1.300; P = 0.443). CONCLUSIONS: Our results strongly suggest that PMX-HP reduces all-cause hospital mortality and length of ICU stay in patients with septic shock.
Subject(s)
Disseminated Intravascular Coagulation/mortality , Hemoperfusion/methods , Polymyxin B/pharmacology , Shock, Septic/drug therapy , Aged , Aged, 80 and over , Cohort Studies , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/prevention & control , Female , Hemoperfusion/standards , Humans , Intensive Care Units/organization & administration , Japan , Male , Middle Aged , Odds Ratio , Polymyxin B/therapeutic use , Propensity Score , Retrospective Studies , Shock, Septic/mortality , Survival AnalysisABSTRACT
Smoldering-type and chronic-type adult T-cell leukemia/lymphomas (ATLL) patients have relatively indolent clinical courses, but often progress into aggressive lymphoma-type and acute-type disease. We examined the roles of transcription factor C-MYC and its ubiquitin ligase FBXW7 in tumor tissues from 137 patients with ATLL. Immunohistochemical tests showed ≥50% of lymphoma cells in 78.7% (48/61) of lymphoma-type, and 64.9% (24/37) of acute-type samples expressed C-MYC, significantly higher than was seen in smoldering-type (3.6%) and chronic-type (9.1%) samples (P<0.01). Real-time polymerase chain reaction showed C-MYC mRNA expression in lymphoma-type and acute-type samples were significantly higher than in smoldering-type (P<0.01). C-MYC expression was highly correlated with its mRNA levels (ρ=0.65, P<0.0001), chromosomal amplification and duplication (ρ=0.3, P=0.045) and MIB1 labeling index (ρ=0.69, P<0.0001). Expression of FBXW7 protein and mRNA in lymphoma-type samples were significantly lower than those of smoldering-type (P<0.01 for each), and both were inversely correlated with C-MYC (protein: ρ=-0.4, P=0.0002; mRNA: ρ=-0.31, P=0.015). Seven patients with smoldering-type or chronic-type ATLL converted to acute-type, in 4 of whom C-MYC expression increased from <50% to ≥50%. Patients with ≥50% C-MYC or MIB1 had significantly worse prognosis than those with <50% C-MYC (P=0.0004) or MIB1 (P<0.0001), as did those with ≥7.5 C-MYC mRNA scores (P=0.033); whereas significantly better prognosis was associated with ≥50% FBXW7 protein (P=0.0006) or ≥0.17 FBXW7 mRNA (P=0.016). C-MYC and FBXW7 affect ATLL proliferation and progression, and low FBXW7 may increase C-MYC expression. C-MYC was a critical prognostic factor in ATLL patients.