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1.
Psychooncology ; 28(8): 1687-1694, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31267595

RESUMO

OBJECTIVE: The objective of the study is to investigate depressive symptoms before and after the initiation of chemotherapy and their impact on overall survival (OS) among patients with hematological malignancies. METHODS: We performed a prospective analysis of consecutive patients with newly diagnosed malignant lymphoma or multiple myeloma enrolled between September 2010 and March 2016. We evaluated depression symptoms at two time points: before starting chemotherapy (T1) and 1 month later (T2), using PHQ-9 and known prognostic factors. We allocated participants with depressive symptoms at T1 and/or T2 to a depression group that was subdivided as follows: new depressive symptoms at T2, ("new-onset"), remission of depressive symptoms at T2 ("remission"), and persistent depressive symptoms from T1 to T2 ("persistent"). The main outcome, OS, was evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards modeling. RESULTS: Of the 294 eligible participants, we analyzed 255 patients, including 83 with depression. There were 19 participants in the new-onset, 38 in the remission, and 26 in the persistent depression group. The OS of participants with depression was significantly shorter than that of those without depression (adjusted hazard ratio [AjHR] 2.43; 95% confidence interval [CI] 1.43-4.12; P < .001). Using the never-depressive symptoms group as a reference group, AjHRs were as follows: new-onset, 1.91 (95% CI, 0.77-4.75; 0.166); remission, 2.98 (95% CI, 1.55-5.74; 0.001), and persistent, 2.17 (95%CI, 1.01-4.68; 0.047). CONCLUSIONS: Among patients with mature lymphoid malignancy, the group with depression at baseline had a poorer survival, both in the group that remained depressive and the group that recovered from depressive symptoms.

2.
Ultrasound Med Biol ; 45(8): 1970-1976, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31064699

RESUMO

Femoral anteversion has been assessed with ultrasound using femoral neck tilting angle (FN-TA); however, femoral torsion angle (FTA), which is defined using FN-TA and condylar axis tilting angle, has not been assessed with ultrasound. This study aimed to establish the ultrasonographic assessment of FTA (US-FTA) by comparing data obtained through US-FTA and computed tomography (CT). Twenty-one patients (age range, 38-82 y) with 21 intact hips were included. In the US-FTA, the femoral head and anterior tubercle of the greater trochanter were used as bony landmarks. The intra-rater and inter-rater reliabilities and standard error of measurement (SEM) of US-FTA were 0.994 (SEM 0.93) and 0.994 (SEM 0.94), respectively. A strong agreement was found between FTA variables obtained with ultrasound and CT (R = 0.939, p < 0.001). Ultrasound is useful and can be a valid alternative to CT for the evaluation of the femoral torsion angle without radiation exposure.

3.
J Invest Dermatol ; 139(6): 1329-1338.e7, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30776434

RESUMO

Chronic low-grade inflammation can cause several metabolic syndromes. Patients with psoriasis, a chronic immunological skin inflammation, often develop diabetes. However, it is not clear to date how psoriasis leads to, or is correlated with, glucose intolerance. Here, we investigate whether psoriasis itself is correlated with hyperglycemia in humans and mice. In patients, the severity of psoriasis was correlated with high blood glucose levels, and treatment of psoriasis by phototherapy improved insulin secretion. Imiquimod-induced systemic and cutaneous inflammation in mice, with features of human psoriasis, also resulted in hyperglycemia. Although it should be determined if psoriasis-like cutaneous inflammation alone can induce hyperglycemia, imiquimod-treated mice showed impairment of insulin secretion without significant islet inflammation. Administration of anti-IL-17A monoclonal antibody improved hyperglycemia in patients with psoriasis and imiquimod-treated mice with psoriasiform features. These results suggest that hyperglycemia is highly associated with psoriasis, mainly through IL-17.

4.
Jpn J Clin Oncol ; 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508206

RESUMO

Background: The family members of terminally ill patients are often requested to make difficult surrogate decisions during palliative care. This study sought to clarify the appropriate communication style for physicians as perceived by family members confronting difficult surrogate decision-making. Methods: This experimental psychological study used scripted videos. In the videos, the physician described treatment options including continuous deep sedation to the family members of patients with cancer and terminal delirium using an autonomous or paternalistic style. Medical professionals with clinical experience in oncology were randomly assigned to either group viewing the videos. The primary outcomes were physician compassion, decisional conflict and emotion scores. We also evaluated the communication style preference. Results: In total, 251 participants completed this study. Although participants in both groups reported high physician compassion, participants in the autonomous style group reported lower compassion scores (reflecting higher physician compassion) (mean 15.0 vs. 17.3, P = 0.050), lower decisional conflicts scores (51.1 vs. 56.8, P = 0.002) and comparable emotions compared with those in the paternalistic style group. Seventy-six percent of participants preferred the autonomous style. Conclusions: Regarding difficult surrogate decision-making, the autonomous style might be more appropriate than the paternalistic style. However, various factors, such as family members' communication style preferences, family members' values, physician-family relationships and ethnic cultures, should be considered.

5.
Surg Today ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30511319

RESUMO

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) lobectomy is performed widely for patients with clinical stage I non-small cell lung cancer (NSCLC) because of its superior short-term outcomes to those of thoracotomy lobectomy. However, the long-term outcomes of VATS lobectomy vs. thoracotomy lobectomy remain controversial. METHODS: We reviewed the clinical data of 202 consecutive patients who underwent lobectomy for clinical stage IA NSCLC at our institution between January, 2008 and December, 2013. Stage IA NSCLC was confirmed pathologically in 162 of these patients, 60 of whom underwent VATS lobectomy and 102 of whom underwent thoracotomy lobectomy. We compared the perioperative clinical factors and outcomes of these two groups, using a propensity score-matched analysis. RESULTS: In an analysis of 58 matched cases, the VATS group showed less blood loss, a shorter duration of chest tube placement, a shorter postoperative hospital stay, and a lower peak C-reactive protein value, despite a longer operative time. The VATS group also had significantly longer survival than the thoracotomy group [5-year overall survival, 100% vs. 87%, respectively (p = 0.01); 5-year disease-free survival, 100% vs. 86% (p = 0.03)]. CONCLUSIONS: These findings suggest that VATS may have better long-term as well as short-term outcomes than thoracotomy for patients with early-stage NSCLC.

6.
Mod Rheumatol ; : 1-16, 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30334636

RESUMO

OBJECTIVES: The aim of the present study was to determine if the HLA phenotype is related to severe sacroiliitis in Japanese patients with psoriatic arthritis. METHODS: This study was a single-center, retrospective, cross-sectional, observational study. We reviewed the clinical information and radiologic examinations of patients with psoriatic arthritis (PsA) who visited our hospital from January 2011 to December 2016. Radiographic changes in the sacroiliac joints were assessed by four independent investigators according to the recommendations of the Assessment of Spondyloarthritis International Society. RESULTS: Of 113 PsA patients, 63 (55.8%) had sacroiliitis. The HLA phenotype was investigated in 39 patients. Ordered logistic regression analysis revealed that the presence of HLA-B46 was an independent risk factor for severe sacroiliitis in Japanese PsA patients (odds ratio 3.2; 95% confidence interval 1.16-9.81). Therefore, the clinical features were divided into two groups according to the presence of HLA-B46. Both the Nail Psoriasis Severity Index and grade of sacroiliitis were significantly higher in the HLA-B46-positive group (Mann-Whitney U test; p = 0.0003 and p = 0.028, respectively). CONCLUSIONS: HLA-B46 is considered a risk factor for severe sacroiliitis in Japanese patients with PsA.

7.
Nagoya J Med Sci ; 80(3): 357-366, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30214085

RESUMO

Some patients undergo postoperative chemotherapy despite showing impaired wound healing after a major surgery. We speculated that postoperative chemotherapy further delays wound healing in these patients. This study aimed to compare the effects of doxorubicin (DXR) in ischemic skin flap and normal incisional wound models after surgery. A 2-cm incisional wound was made in group 1 rats, and saline was injected intravenously, following surgery on the same day. Incisional wound was made in group 2-5 rats, and 8 mg/kg DXR was injected intravenously, following surgery on the same day and after 7, 14, and 21 days respectively. H-shaped double flaps were made in group 6 rats, and saline was injected intravenously, following surgery on the same day. Flaps were made in group 7-10 rats, and 8 mg/kg DXR was injected intravenously, following surgery on the same day and after 7, 14, and 21 days respectively. On days 7, 14, 21, and 28 after surgery, the suture wounds were removed, tensile wound strengths were measured, and tissue samples were collected for histopathological evaluation. The tensile strength was significantly lower in the DXR-treated groups than in the control groups for both ischemic skin flaps and incision wounds. Additionally, the cross effect between DXR and ischemia was not significant. On pathological examination, DXR showed atrophic skin changes and degeneration of skin appendages on days 14-21 after the surgery in both the models. DXR decreased the wound tensile strength and caused an atrophic change in the ischemic wound.

8.
Artigo em Inglês | MEDLINE | ID: mdl-30230963

RESUMO

Therapeutic hypothermia following neonatal encephalopathy is neuroprotective. However, approximately one in two cooled infants still die or develop permanent neurological impairments. Further understanding of variables associated with the effectiveness of cooling is important to improve the therapeutic regimen. To identify clinical factors associated with short-term outcomes of cooled infants, clinical data of 509 cooled infants registered to the Baby Cooling Registry of Japan between 2012 and 2014 were evaluated. Independent variables of death during the initial hospitalization and survival discharge from the cooling hospital at ≤28 days of life were assessed. Death was associated with higher Thompson scores at admission (p < 0.001); higher heart rates after 3-72 hours of cooling (p < 0.001); and higher body temperature after 24 hours of cooling (p = 0.002). Survival discharge was associated with higher 10 minutes Apgar scores (p < 0.001); higher blood pH and base excess (both p < 0.001); lower Thompson scores (at admission and after 24 hours of cooling; both p < 0.001); lower heart rates at initiating cooling (p = 0.003) and after 24 hours of cooling (p < 0.001) and lower average values after 3-72 hours of cooling (p < 0.001); higher body temperature at admission (p < 0.001); and lower body temperature after 24 hours and lower mean values after 3-72 hours of cooling (both p < 0.001). Survival discharge was best explained by higher blood pH (p < 0.05), higher body temperature at admission (p < 0.01), and lower body temperature and heart rate after 24 hours of cooling (p < 0.01 and <0.001, respectively). Lower heart rate, higher body temperature at admission, and lower body temperature during cooling were associated with favorable short-term outcomes.

9.
J Palliat Med ; 21(10): 1436-1441, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29893612

RESUMO

BACKGROUND: Preclinical studies show that opioids promote angiogenesis, tumor progression, and metastasis, resulting in shorter survival. OBJECTIVE: To explore whether opioids are associated with the overall survival (OS) of patients with incurable nonsmall cell lung cancer (NSCLC). DESIGN: Prospective cohort study of patients with NSCLC. SETTING: We investigated patients newly diagnosed with advanced or post-operative recurrent NSCLC between April 2013 and December 2015 at a single institute. MEASUREMENTS: We evaluated OS, opioid requirements, opioid doses, pain levels, and prognostic factors of advanced NSCLC. The effects of variables on survival were analyzed using univariable and multivariable models. Patients were stratified according to oral morphine equivalents (OMEs)/day (<60 or ≥60 mg) to assess the association between opioid dose and OS. RESULTS: We analyzed 150 patients, including 64 who received opioid treatment during follow-up. The median OS was 242 days in the opioid group and 627 days in the no-opioid group (log-rank p < 0.001). Multivariable models revealed that the opioid requirement was an independent predictor of shorter OS, after adjustment for prognostic variables, including sex, histology, stage, history of systemic chemotherapy, and performance status (hazard ratio 1.73, 95% confidence interval 1.137-2.631). There was no significant difference in OS between patients who received ≥60 mg OME/day for 250 days versus <60 OME/day for 242 days. CONCLUSIONS: The opioid dose does not shorten the survival of patients with advanced NSCLC. The opioid requirement is associated with shorter survival when opioids are administered any time during the clinical course, independent of the influence of other key factors.

10.
Leukemia ; 2018 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-29946189

RESUMO

Studies have previously shown that mutant calreticulin (CALR), found in a subset of patients with myeloproliferative neoplasms (MPNs), interacts with and subsequently promotes the activation of the thrombopoietin receptor (MPL). However, the molecular mechanism behind the activity of mutant CALR remains unknown. Here we show that mutant, but not wild-type, CALR interacts to form a homomultimeric complex. This intermolecular interaction among mutant CALR proteins depends on their carboxyl-terminal domain, which is generated by a unique frameshift mutation found in patients with MPN. With a competition assay, we demonstrated that the formation of mutant CALR homomultimers is required for the binding and activation of MPL. Since association with MPL is required for the oncogenicity of mutant CALR, we propose a model in which the constitutive activation of the MPL downstream pathway by mutant CALR multimers induces the development of MPN. This study provides a potential novel therapeutic strategy against mutant CALR-dependent tumorigenesis via targeting the intermolecular interaction among mutant CALR proteins.

11.
J Neurosci ; 38(19): 4598-4609, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29661967

RESUMO

In the rodent olfactory system, neuroblasts produced in the ventricular-subventricular zone of the postnatal brain migrate tangentially in chain-like cell aggregates toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After reaching the OB, the chains are dissociated and the neuroblasts migrate individually and radially toward their final destination. The cellular and molecular mechanisms controlling cell-cell adhesion during this detachment remain unclear. Here we report that Fyn, a nonreceptor tyrosine kinase, regulates the detachment of neuroblasts from chains in the male and female mouse OB. By performing chemical screening and in vivo loss-of-function and gain-of-function experiments, we found that Fyn promotes somal disengagement from the chains and is involved in neuronal migration from the RMS into the granule cell layer of the OB. Fyn knockdown or Dab1 (disabled-1) deficiency caused p120-catenin to accumulate and adherens junction-like structures to be sustained at the contact sites between neuroblasts. Moreover, a Fyn and N-cadherin double-knockdown experiment indicated that Fyn regulates the N-cadherin-mediated cell adhesion between neuroblasts. These results suggest that the Fyn-mediated control of cell-cell adhesion is critical for the detachment of chain-forming neuroblasts in the postnatal OB.SIGNIFICANCE STATEMENT In the postnatal brain, newly born neurons (neuroblasts) migrate in chain-like cell aggregates toward their destination, where they are dissociated into individual cells and mature. The cellular and molecular mechanisms controlling the detachment of neuroblasts from chains are not understood. Here we show that Fyn, a nonreceptor tyrosine kinase, promotes the somal detachment of neuroblasts from chains, and that this regulation is critical for the efficient migration of neuroblasts to their destination. We further show that Fyn and Dab1 (disabled-1) decrease the cell-cell adhesion between chain-forming neuroblasts, which involves adherens junction-like structures. Our results suggest that Fyn-mediated regulation of the cell-cell adhesion of neuroblasts is critical for their detachment from chains in the postnatal brain.

12.
Neurourol Urodyn ; 37(4): 1258-1265, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29112292

RESUMO

OBJECTIVE: To investigate whether c-kit ligand, stem cell factor (SCF) affects the biological behavior of overactive bladder (OAB) and discuss the role of SCF as a possible mediator inducing OAB. MATERIALS AND METHODS: First, we performed an immunohistochemical study to examine the localization of SCF in the guinea pig and human bladder. Next, urinary SCF levels were measured in patients with OAB and in control subjects to evaluate a potential biomarker for the diagnosis of OAB. Third, we examined the effect of SCF administration on the urinary bladder using guinea pigs to obtain additional information about SCF. The animals were administered with mouse SCF, and cystometry was performed. The following urodynamic parameters were analyzed: inter-contraction interval, maximum voiding pressure, pressure threshold, detrusor baseline pressure, and the number of non-voiding contractions. RESULTS: Immunohistochemical study showed that the expression of SCF was observed throughout the bladder wall, but especially in the urothelium of guinea pig and human bladder. Medians and IQRs of urinary SCF and SCF/creatinine levels in OAB patients (85.9 pg/mL [42.8, 199.0] and 1.30 [0.56, 2.71], respectively) were significantly higher than in control subjects (18.9 pg/mL [5.0, 43.6] and 0.26 [0.13, 0.43], respectively). SCF administration dose-dependently shortened the intercontraction interval and an increased number of non-voiding contractions (P < 0.05). CONCLUSIONS: Our present data suggest that SCF produced in the urinary bladder may act as a possible mediator by binding to c-kit, which is expressed in ICC-like cells in the suburothelial and muscle layers, to control bladder function.

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