RESUMO
Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy. Patients who visited the outpatient clinic of the General Medicine Department of Ogaki Municipal Hospital and received steroids were enrolled. The rates of DXA implementation and compliance with GIO pharmacotherapy guidelines before and after pharmacist to physician-suggested interventions were compared. Guideline compliance was defined as prescription of osteoporosis drugs to patients with a score of ≥3. Administered prophylaxes and bone mineral density were subsequently assessed. The before and after intervention DXA rates were 1% (1/100 patients) and 96.0% (96/100 patients; P<0.01), respectively. Overall, 96.9% (93/96) of the patients met the GIO criteria for pharmacotherapy initiation (score ≥3), and the guideline compliance rates before and after the intervention were 39.8% (37/93) and 93.5% (87/93; P<0.01), respectively. Of the 56 patients who did not receive prophylaxis, 52 were recommended treatment, yielding an acceptance rate of 82.7% (43/52). Among the 37 patients receiving prophylaxis, 20 (54.1%) had a DXA-related young adult mean of ≤70%, of whom 11 (55.0%) agreed to drug therapy. The acceptance rate of pharmacotherapy recommendations for patients not receiving prophylaxis was higher than that for those receiving prophylaxis (P=0.03). Pharmacist-initiated interventions for GIO facilitates the administration of appropriate pharmacotherapy.
Assuntos
Absorciometria de Fóton , Conservadores da Densidade Óssea , Densidade Óssea , Glucocorticoides , Fidelidade a Diretrizes , Osteoporose , Farmacêuticos , Humanos , Densidade Óssea/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Feminino , Masculino , Idoso , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Pessoa de Meia-Idade , Conservadores da Densidade Óssea/administração & dosagem , Idoso de 80 Anos ou mais , AdultoRESUMO
We report here the first observation of the 0_{2}^{+} state of ^{8}He, which has been predicted to feature the condensatelike α+^{2}n+^{2}n cluster structure. We show that this state is characterized by a spin parity of 0^{+}, a large isoscalar monopole transition strength, and the emission of a strongly correlated neutron pair, in line with theoretical predictions. Our finding is further supported by the state-of-the-art microscopic α+4n model calculations. The present results may lead to new insights into clustering in neutron-rich nuclear systems and the pair correlation and condensation in quantum many-body systems under strong interactions.
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Vincristine (VCR) is an important drug used in R-CHOP regimens for the treatment of non-Hodgkin's lymphoma. The purpose of this study was to examine whether the administration method affects the incidence of VCR-induced peripheral neuropathy. We investigated the ratio of VCR-induced peripheral neuropathy during rapid intravenous infusion and intravenous drip infusion. A total of 71 patients who had received six or more courses of R-CHOP from January, 2015 to December, 2016 at Komaki City Hospital and Ogaki Municipal Hospital were retrospectively investigated. Peripheral neuropathy was observed in 27/39 patients (69 %) and 24/32 (75 %) in rapid intravenous infusion and intravenous drip infusion of VCR, respectively (P = 0.79). Peripheral neuropathy was observed at a high frequency in this study. Additionally, there was no difference in frequency of peripheral neuropathy due to the difference in administration method. In both groups, the degree of peripheral neuropathy was grade 1 and grade 2 in most patients. However, in rapid intravenous infusion, grade 3 peripheral neuropathy was observed. Some cases required dose reduction and discontinuation in rapid intravenous infusion. In contrast, there were no discontinuing patients in the intravenous drip infusion. Therefore, it was suggested that intravenous drip infusion of VCR reduced serious peripheral neuropathy because the ratio requiring dose reduction and discontinuation was less than that in the rapid group. In conclusion, this study is informative as there are few reports focusing on the administration method of vincristine.
Assuntos
Linfoma não Hodgkin , Doenças do Sistema Nervoso Periférico , Doxorrubicina/efeitos adversos , Humanos , Infusões Intravenosas , Linfoma não Hodgkin/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/patologia , Estudos Retrospectivos , Vincristina/efeitos adversosRESUMO
A kinematically complete quasifree (p,pn) experiment in inverse kinematics was performed to study the structure of the Borromean nucleus ^{17}B, which had long been considered to have a neutron halo. By analyzing the momentum distributions and exclusive cross sections, we obtained the spectroscopic factors for 1s_{1/2} and 0d_{5/2} orbitals, and a surprisingly small percentage of 9(2)% was determined for 1s_{1/2}. Our finding of such a small 1s_{1/2} component and the halo features reported in prior experiments can be explained by the deformed relativistic Hartree-Bogoliubov theory in continuum, revealing a definite but not dominant neutron halo in ^{17}B. The present work gives the smallest s- or p-orbital component among known nuclei exhibiting halo features and implies that the dominant occupation of s or p orbitals is not a prerequisite for the occurrence of a neutron halo.
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This study aimed to identify the overall survival prolongation index in patients who received paclitaxel plus ramucirumab as second line chemotherapy for human epidermal growth factor receptor (HER) 2-negative advanced/ recurrent gastric cancer (AGC). We included 77 patients who underwent second line chemotherapy (paclitaxel plus ramucirumab) for AGC at our institution between January 2015 and September 2020. To determine factors associated with survival, univariate and multivariate analyses were performed, and hazard ratios and their 95% confidence intervals (95% CI) were calculated. In the multivariate analysis, grade ≥1 neutropenia (yes) and the number of anti-cancer drugs used (≥5) were independently and significantly associated with survival. Compared to the patients without grade ≥1 neutropenia, patients with grade ≥1 neutropenia had a survival hazard ratio of 0.455 (95% CI: 0.214-0.966; p = 0.040). The median second line treatment durations in patients with grade ≥1 neutropenia (n = 54) and in those without grade ≥1 neutropenia (n = 23) were 133 days (95% CI, 98-190 days) and 70 days (95% CI, 41-128 days), respectively (log-rank test, p = 0.026). This study demonstrated that AGC patients with initial neutropenia may benefit from paclitaxel plus ramucirumab therapy.
Assuntos
Neoplasias Gástricas , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel , Prognóstico , Receptor ErbB-2 , Neoplasias Gástricas/tratamento farmacológico , RamucirumabRESUMO
We retrospectively evaluated the incidence of skin immune-related adverse effects (irAEs) in patients treated with pembrolizumab (PMB) and explored and the relationship between skin irAEs and PMB efficacy. Thirty-two patients with non-small cell lung cancer treated with PMB between April 2017 and May 2018 were enrolled. The patients were separated into two groups, namely, skin irAEs and no-skin irAEs group. We investigated the ratio and degree of express skin irAEs, period of skin irAEs and treatment, and the PFS between the two groups. Additionally, we evaluated the PFS between the irAE and no-irAEs groups. The median patient age was 76.5 (range 56-92) years. The European Cooperative Oncology Group Performance Status (ECOG PS) score of 26, 5, and 1 was 0-1, 2, and 3, respectively. The male/female ratio was 23/9. In terms of clinical stages, 6, 21, and 5 patients were in stages III and IV, and postoperative relapse, respectively. Skin irAEs were observed in 10 patients (31%). The progression-free survival of patients with skin irAEs (median, 390 days) was longer than that of patients without skin irAEs (median, 128.5 days). Overall, we suggested a significant association between skin irAEs and the efficacy of PMB in treating non-small cell lung cancer. As skin irAEs can be an indicator of treatment efficacy, it is important for medical staff, including pharmacists, to closely observe these adverse events.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Anormalidades da Pele/etiologia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele/imunologia , Resultado do TratamentoRESUMO
An inelastic excitation and cluster-decay experiment ^{2}H(^{16}C,^{4}He+^{12}Be or ^{6}He+^{10}Be)^{2}H was carried out to investigate the linear-chain clustering structure in neutron-rich ^{16}C. For the first time, decay paths from the ^{16}C resonances to various states of the final nuclei were determined, thanks to the well-resolved Q-value spectra obtained from the threefold coincident measurement. The close-threshold resonance at 16.5 MeV is assigned as the J^{π}=0^{+} band head of the predicted positive-parity linear-chain molecular band with (3/2_{π}^{-})^{2}(1/2_{σ}^{-})^{2} configuration, according to the associated angular correlation and decay analysis. Other members of this band were found at 17.3, 19.4, and 21.6 MeV based on their selective decay properties, being consistent with the theoretical predictions. Another intriguing high-lying state was observed at 27.2 MeV which decays almost exclusively to ^{6}He+^{10}Be(â¼6 MeV) final channel, corresponding well to another predicted linear-chain structure with the pure σ-bond configuration.
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This study aimed to clarify the relationship between neutropenia and progression-free survival (PFS) under palbociclib treatment for advanced/recurrent breast cancer and the risk factors for severe neutropenia. We retrospectively identified 37 patients who received palbociclib for advanced breast cancer at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and June 2020. Kaplan-Meier log-rank test was used to compare PFS (mild [neutrophil count 1,000-2,000/mm 3 ] versus severe [neutrophil count <500-1,000/mm³]). Multivariate analysis was performed to evaluate the relationships between baseline patient characteristics and severe neutropenia development. There were three, four, 25, and five cases with grade 1, 2, 3, and 4 neutropenia, respectively. Median PFS in patients who developed severe neutropenia (n = 30) and those who did develop mild neutropenia (n = 7) was 176 days (range: 62-894 days) and 91 days (range: 19-384 days), respectively (log-rank test, p = 0.005). Severe neutropenia was independently associated with pre-treatment neutrophil count (odds ratio: 27.700; p =0.007). Severe neutropenia is more likely to occur with a pre-treatment neutrophil count of less than 3,680 mm³. Neutropenia prolongs PFS under palbociclib treatment, suggesting management of AEs and patient education as highly important, especially to prevent drug interruption/dose reduction of palbociclib due to these AEs.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Piperazinas/uso terapêutico , Intervalo Livre de Progressão , Piridinas/uso terapêutico , Idoso , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Neutropenia/mortalidade , Estudos RetrospectivosRESUMO
Long-term azacitidine (AZA) treatment is necessary for its maximal therapeutic effect. This study examined the continuity and efficacy of AZA treatment in real-world use. We conducted a retrospective study in 38 patients who had completed AZA treatment at the Ogaki Municipal Hospital between April 2011 and August 2019. The median number of AZA received cycles was 4. The number of AZA treatment cycles received was 1-3 cycles in 15 (39.5%), 4-6 cycles in 15 (39.5%), and ≥ 7 cycles in 8 (21.1%). The most common reason for discontinued AZA treatment was infection. Overall response rate was 33.3% in patients with discontinued AZA use (< 4 cycles) and 56.5% in patients with continued AZA (≥ 4). Median overall survival (OS) was 124 (15-529) days and 391 (132-2,825) days in the respective groups (p<0.01). The presence of peripheral blood blasts (PBs) was a prognostic factor for continuation of treatment (p =0.03). Discontinued AZA treatment due to infection (p <0.01), and PBs (p =0.03) were unfavourable prognostic factors for OS. Long-term AZA use is beneficial for improvement and survival. Infection control and presence of PBs were important factors for continuing AZA. These data support the idea of long-term continued treatment with AZA for optimal benefit to patients.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Feminino , Humanos , Infecções/complicações , Infecções/epidemiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
AIM: To investigate the proliferation and mineralization of a human cementoblast cell line under alkaline conditions. METHODOLOGY: A human cementoblast cell line was cultured in alkaline media with several pHs (pH 7.6, 8.0 and 8.4) without CO2 . Cell numbers, phospho-p44/42 expression, alkaline phosphatase (ALP) activity and mineralization were evaluated. The significance of differences between groups was assessed using two-way analysis of variance 15 (ANOVA) followed by Bonferroni's multiple comparison test (α = 0.01). RESULTS: Cell numbers increased in a time-dependent manner in the high pH medium groups. Western blot analysis revealed the upregulated expression of phospho-p44/42 under alkaline conditions. ALP activity was also increased at pH 8.0 and 8.4. Alizarin red staining revealed increased mineralization in the high pH medium groups. The incorporation of the transient receptor potential ankyrin subfamily member 1 (TRPA1) antagonist HC030031 markedly negated the effect on proliferation and mineralization. CONCLUSIONS: Extracellular alkaline conditions promoted the proliferation and mineralization of human cementoblasts in vitro via TRPA1.
Assuntos
Fosfatase Alcalina , Cemento Dentário , Calcificação Fisiológica , Contagem de Células , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Células Cultivadas , HumanosRESUMO
OBJECTIVE: Vertical jump height and oral function affect the general muscle condition. This study aimed to evaluate the association between vertical jump height and oral function among healthy older individuals. BASIC RESEARCH DESIGN: Cross-sectional analytic study. PARTICIPANTS: 231 independent older people (mean age, 74.4 ± 5.6 years) who participated in the Kyoto Elders Physical Fitness Measurement Research Project. Individuals with partial or complete edentulousness who did not use a prosthetic device or complained of oral/maxillofacial pain were excluded from the study. INTERVENTIONS: Grip strength was measured using a Smedley Hand Dynamometer. To measure masticatory performance, the participants were instructed to chew a gummy jelly on their habitual chewing side (left or right) for 20 s. Occlusal force, contact area, and pressure were also assessed. MAIN OUTCOME MEASURES: The outcome variable was vertical jump height. The predictor variables were physical status (age, body mass index, and grip strength), oral status (number of present teeth and denture use), and oral function (masticatory performance, occlusal force, occlusal contact area, occlusal pressure, and tongue pressure). These relationships were evaluated with univariate analysis, and then multiple regression analysis was performed with age as the covariate for each male and female participant. RESULTS: Vertical jump height was significantly associated with grip strength in both men and women. Moreover, in women, it was associated with masticatory performance, occlusal force, and occlusal contact area. CONCLUSIONS: Vertical jump height was closely associated with oral function among healthy older women.
Assuntos
Força de Mordida , Língua , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Mastigação , PressãoRESUMO
This retrospective study compares the economic superiority of palbociclib versus everolimus for advanced and recurrent breast cancer. Furthermore, we investigated the safety and treatment continuity of palbociclib and everolimus regimens. Expected costs were calculated based on data from patients with advanced and recurrent breast cancer who were treated with palbociclib and everolimus. The progression-free survival (PFS) from the PALOMA-3 clinical trial and BOLERO-2 clinical trial was used to evaluate the therapeutic efficacy of the regimens. The cost-effectiveness ratio of each chemotherapy agent was calculated by dividing the expected cost by the progression-free survival (PFS). The cost-effectiveness ratio per month was JPY 391,551.3/PFS for palbociclib and JPY 488,690.5/PFS for everolimus (p=0.627). The incremental cost-effectiveness ratio per month of everolimus to palbociclib was JPY 100,133.7/PFS. For patients receiving everolimus, adverse drug reactions included stomatitis (77.3%), rash (59.1%) and leukopenia (59.1%). For patients receiving palbociclib, neutropenia (69.2%), leukopenia (69.2%) and anemia (30.8%) occurred. In terms of discontinuation owing to adverse events (AEs), pneumonitis, thrombocytopenia, edema, fatigue, and neutropenia were experienced in the everolimus group. The cost-effectiveness of everolimus and palbociclib are equivalent, but since the prevalence of AEs is high in patients receiving everolimus, its AE management is important.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Everolimo/economia , Everolimo/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Piperazinas/economia , Piperazinas/uso terapêutico , Piridinas/economia , Piridinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Everolimo/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Piridinas/efeitos adversosRESUMO
S-1 and cisplatin therapy (SP therapy) is widely used as the first-line of advanced/recurrent gastric cancer. However, severe neutropenia is often observed (40%) during this therapy. Therefore, the risk management of neutropenia is important. From September 2014 to April 2017, we investigated 76 patients who underwent SP therapy as primary treatment for advanced/recurrent gastric cancer at Ogaki Municipal Hospital. Risk factors for grade 3/4 neutropenia were examined by univariate and multivariate analyses. In SP therapy, 19 patients (25%) experienced grade 3/4 neutropenia. The results of multivariate analysis of factors with p <0.05 in the univariate analysis indicated that less than 10.6 g/dL of the haemoglobin value before the course at the lowest neutrophil count (odds ratio: 7.900; 95% CI: 1.280-48.60; p = 0.026), more than six courses of the total course (odds ratio: 9.13; 95% CI: 2.13-39.1; p = 0.003), and less than 3140 m2 neutrophil counts (odds ratio: 5.33; 95% CI: 1.47-19.3; p = 0.011) before chemotherapy were risk factors of grade 3/4 neutropenia. A low haemoglobin value before the course at the lowest neutrophil count was revealed as a risk factor causing severe neutropenia in SP therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Neoplasias Gástricas/complicações , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Combinação de Medicamentos , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neutrófilos/efeitos dos fármacos , Ácido Oxônico/administração & dosagem , Fatores de Risco , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagemRESUMO
Vitamin (V) K deficiency may cause severe bleeding tendencies, which necessitates extreme caution. We report a case of a 30-year-old man diagnosed with VK deficiency of unknown etiology. He was treated with intravenous menatetrenone three times a week in an outpatient setting for about 1 year and 9 months. Eventually, he developed an allergic reaction to intravenous menatetrenone and was under steroid therapy. In order to reduce his hospital visits and discontinue steroid use, the pharmacist proposed to change the method of menatetrenone administration from intravenous to oral (high dose). The change in treatment method has greatly improved the patient's quality of life.
Assuntos
Hemostáticos/efeitos adversos , Hemostáticos/uso terapêutico , Vitamina K 2/análogos & derivados , Deficiência de Vitamina K/terapia , Administração Intravenosa , Administração Oral , Adulto , Hipersensibilidade a Drogas/tratamento farmacológico , Hemostáticos/administração & dosagem , Humanos , Masculino , Qualidade de Vida , Esteroides/uso terapêutico , Vitamina K 2/administração & dosagem , Vitamina K 2/efeitos adversos , Vitamina K 2/uso terapêuticoRESUMO
For patients with advanced/recurrent colorectal cancer, the trifluridine/tipiracil combination tablet (TAS 102) and regorafenib are last-line treatments. This study aimed to clarify prognostic factors in patients receiving last-line chemotherapy. Between April 2014 and December 2016, 47 patients received last-line chemotherapy at Ogaki Municipal Hospital, Japan. The primary outcome was overall survival. To determine factors associated with survival, those considered significant in the univariate analysis (p <0.10), were entered into a multivariate Cox proportional hazards model. KRAS type and the use of opioid formulations were independently and significantly associated with survival in the multivariate analysis. For patients with KRAS-wild relative to KRAS-mutation cancers, the hazard ratio for death was 0.478 (95% CI, 0.249-0.919; p = 0.03). For patients taking opioid formulations, relative to those not, the hazard ratio for death was 3.557 (95% CI, 1.032-12.257; p = 0.04). The median overall survival duration for patients with KRAS-wild (n = 24) and KRAS-mutation (n = 23) cancers were 223.5 days (range: 115-703) and 154 days (range: 51-503), respectively (p = 0.05). This finding provides a useful index to make an early decision on discontinuation of treatment and to guide decisions around agents to use in last-line chemotherapy.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Dor do Câncer/tratamento farmacológico , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Análise de SobrevidaRESUMO
As a result of the RAINBOW trial, ramucirumab plus paclitaxel was established as a second-line treatment of advanced gastric cancer. Regarding the safety of ramucirumab plus paclitaxel in the Japanese, a subgroup analysis of the RAINBOW trial was conducted. The incidence of neutropenia was higher in Japanese patients. However, information is lacking concerning the safety of ramucirumab after marketing in Japanese patients. Therefore, the aim of this study was to evaluate the safety of ramucirumab in Japanese patients with advanced gastric cancer. The inclusion criteria were patients diagnosed with advanced gastric cancer who had commenced treatment with ramucirumab plus paclitaxel or paclitaxel only at Ogaki Municipal Hospital (Gifu, Japan) between January 2015 and December 2016. There were 26 patients in the ramucirumab plus paclitaxel group and 22 patients in the paclitaxel only group. Treatment-related adverse events were documented in 100.0% of the patients in the ramucirumab plus paclitaxel group (Grade 3-4, 73.1%) and 90.9 % of the patients in the paclitaxel only group (Grade 3-4, 45.5 %). The most frequently observed adverse event in both treatment groups was anemia. The second common adverse event was neutropenia. The incidence of neutropenia of Grade ≥3 was significantly higher in the ramucirumab plus paclitaxel group than in the paclitaxel only group. In conclusion, the incidence of neutropenia is high. However, we believe that ramucirumab plus paclitaxel can be safely administered.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Gástricas/sangue , RamucirumabRESUMO
Elucidating the factors influencing severe neutropenia could aid in earlier management of neutropenia during oral trifluridine-tipiracil (TAS-102) chemotherapy in advanced and recurrent colorectal cancer (CRC). This study was conducted to assess the risk of TAS-102-induced grade 3 or more neutropenia. Between August 2014 and July 2017, 60 patients underwent oral TAS-102 monotherapy at Ogaki Municipal Hospital, Japan. The patients were divided into two groups based on the development of grade 3 or more neutropenia (9 patients) or not (51 patients). Risk factors for grade 3 or more neutropenia were examined by univariate and multivariate analyses. Creatinine clearance rate (CrCl) before TAS-102 administration significantly correlated with the incidence of Grade 3 or more neutropenia after TAS-102 administration (odds ratio 6.5, 95% confidence interval 1.14-30.00; p = 0.02). Multivariate analysis revealed that a CrCl of lower than 57.1 mL/min before TAS-102 administration (odds ratio 54.06, 95% confidence interval 2.14-1364.2; p = 0.02) was an independent risk factor significantly contributing to the development of grade 3 or more neutropenia, induced by TAS-102. CrCl < 57.1 mL/min in patients with advanced and recurrent CRC who underwent TAS-102 chemotherapy was associated with grade 3 or more neutropenia.
Assuntos
Neoplasias Colorretais/complicações , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Trifluridina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Creatinina/sangue , Combinação de Medicamentos , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neutrófilos , Pirrolidinas , Estudos Retrospectivos , Fatores de Risco , Timina , Trifluridina/uso terapêutico , Uracila/análogos & derivadosRESUMO
Hepatitis B virus (HBV) reactivation has been reported during antihepatitis C treatment in patients with hepatitis C virus (HCV) and HBV co-infection. We aimed to evaluate the frequency and risk factors of HBV reactivation during anti-HCV therapy and compared those between interferon (IFN)-free direct-acting antiviral (DAA) therapies and IFN-based therapies. Three hundred and twenty-two patients with HCV infection receiving anti-HCV therapy were retrospectively screened. The baseline HBV infection statuses of all eligible patients and the HBV-DNA level of all patients with current or previous HBV infection were examined at the end of treatment. In patients with baseline anti-HBs positivity, changes in anti-HBs titre were evaluated. Of 287 patients who met the inclusion criteria, 157 had current (n=4) or previous (n=153) HBV infection; 85 were treated with IFN-free DAA therapies and 72 were treated with IFN-based therapies. Six patients experienced HBV reactivation (n=2) or HBV reappearance (n=4) after IFN-free DAA therapies, while no patient developed HBV reactivation after IFN-based therapies. The risk factors of HBV reactivation or reappearance were DAA therapies and a reduction in anti-HBs titre to <12 mIU mL-1 by the end of treatment. The decline changes of anti-HBs titre were significantly higher in patients treated with DAA therapies. Although HBV reactivation hepatitis was not observed, three of four patients with HBV reactivation or reappearance after achieving HCV eradication had viremia 8 weeks after completion of therapy. A significant proportion of patients develop HBV reactivation or reappearance without hepatitis after IFN-free DAA therapies. Low levels of anti-HBs and their decrease to <12 mIU mL-1 after treatment are significant risk factors for HBV reactivation or reappearance.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Ativação Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Viral/sangue , Feminino , Hepatite B Crônica/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de RiscoRESUMO
Histone deacetylases (HDACs) play an important role in the regulation of chromatin structure and gene expression. We found that dark pigmentation of Magnaporthe oryzae (anamorph Pyricularia oryzae) ΔMohda1, a mutant strain in which an orthologue of the yeast HDA1 was disrupted by double cross-over homologous recombination, was significantly stimulated in liquid culture. Analysis of metabolites in a ΔMohda1 mutant culture revealed that the accumulation of shunt products of the 1,8-dihydroxynaphthalene melanin and ergosterol pathways were significantly enhanced compared to the wild-type strain. Northern blot analysis of the ΔMohda1 mutant revealed transcriptional activation of three melanin genes that are dispersed throughout the genome of M. oryzae. The effect of deletion of the yeast HDA1 orthologue was also observed in Fusarium asiaticum from the Fusarium graminearum species complex; the HDF2 deletion mutant produced increased levels of nivalenol-type trichothecenes. These results suggest that histone modification via HDA1-type HDAC regulates the production of natural products in filamentous fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Natural products of fungi have significant impacts on human welfare, in both detrimental and beneficial ways. Although HDA1-type histone deacetylase is not essential for vegetative growth, deletion of the gene affects the expression of clustered secondary metabolite genes in some fungi. Here, we report that such phenomena are also observed in physically unlinked genes required for melanin biosynthesis in the rice blast fungus. In addition, production of Fusarium trichothecenes, previously reported to be unaffected by HDA1 deletion, was significantly upregulated in another Fusarium species. Thus, the HDA1-inactivation strategy may be regarded as a general approach for overproduction and/or discovery of fungal metabolites.
Assuntos
Proteínas Fúngicas/genética , Fusarium/enzimologia , Deleção de Genes , Histona Desacetilases/genética , Magnaporthe/enzimologia , Oryza/microbiologia , Doenças das Plantas/microbiologia , Proteínas Fúngicas/metabolismo , Fusarium/genética , Fusarium/metabolismo , Histona Desacetilases/metabolismo , Humanos , Magnaporthe/genética , Magnaporthe/metabolismo , Melaninas/metabolismo , Naftóis/metabolismo , Metabolismo Secundário , Tricotecenos/metabolismoRESUMO
WHAT IS KNOWN AND OBJECTIVE: Glucocorticoid-induced diabetes mellitus (GIDM) increases the risk of diabetes mellitus (DM)-related complications but is generally difficult to detect in clinical settings. The criteria for diagnosing GIDM have not been established. Recently, medical information databases (MIDs) have been used in post-marketing surveillance (PMS) studies. We conducted a pharmacoepidemiological study to develop an algorithm for detecting GIDM using MID. METHODS: We selected 1214 inpatients who were newly prescribed with a typical glucocorticoid, prednisolone, during hospitalization from 2008 to 2014 from an MID of Hamamatsu University Hospital in Japan. GIDM was screened based on fasting blood glucose (FBG) and haemoglobin A1c (HbA1c) levels according to the current Japan Diabetes Society (JDS) DM criteria, and its predictability was evaluated by an expert's review of medical records. We investigated further candidate screening factors using receiver operating characteristics analysis. RESULTS: Sixty-three inpatients were identified by the JDS DM criteria. Of these, 33 patients were definitely diagnosed as having GIDM by expert's review (positive predictive value = 52·4%). To develop a highly predictive algorithm, we compared the characteristics of inpatients diagnosed with definite GIDM and those diagnosed as non-GIDM. The maximum levels of HbA1c in patients with GIDM were significantly higher than those of patients with non-GIDM (66·9 mmol/mol vs. 58·7 mmol/mol, P < 0·001). The patients with GIDM had significantly higher relative increase in maximum level of HbA1c (RIM-HbA1c) than those with non-GIDM (0·3 vs. 0·03, P < 0·001). However, we did not observe a significant difference in those of fasting blood glucose (FBG) levels. We applied the RIM-HbA1c as a second screening factor to improve the detection of GIDM. It showed that a 13% increase in RIM-HbA1c separated patients with from patients without GIDM. WHAT IS NEW AND CONCLUSIONS: Patients with GIDM had significantly higher RIM-HbA1c than patients with non-GIDM. There was a 13% increase in RIM-HbA1c in patients with GIDM compared to the others. Our detection algorithm for GIDM using an MID achieved high sensitivity and specificity, and was superior to one based only on the current JDS DM criteria. Our results suggest that monitoring changes in HbA1c levels is important for detecting GIDM and adds to current diagnostic criteria for type 2 DM.