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Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL cotreatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal-inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. A 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pretreatment HMO mixture in vitro; thus, this ratio was selected and used for low-, middle-, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as BW loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short-chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggest that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.
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Lipopolissacarídeos , Oligossacarídeos , Camundongos , Animais , Oligossacarídeos/farmacologia , Inflamação/tratamento farmacológico , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Trissacarídeos/farmacologia , Lactose/análogos & derivadosRESUMO
AIM: To evaluate the reliability of synthetic diffusion-weighted imaging (DWI) using a high b-value in comparison to conventional DWI for paediatric abdominal MRI. MATERIALS AND METHODS: Paediatric patients (<19 years old) who underwent liver or pancreatobiliary MRI with DWI using 10 b-values (b = 0, 25, 50, 75, 100, 200, 400, 600, 800, 1,500 s/mm2) from March to October 2021 were included in this retrospective study. Using the software, synthetic DWI using b = 1,500 s/mm2 was generated automatically by selecting the b-value required as output. Conventional and synthetic DWI values for b = 1,500 s/mm2 were measured at the liver, spleen, paraspinal muscle, and mass lesions, if present, and apparent diffusion coefficient (ADC) values were calculated using the mono-exponential model. Intraclass correlation coefficients (ICCs) were calculated to assess the reliability of conventional and synthetic DWI and ADC values with b = 1,500 s/mm2. RESULTS: Thirty paediatric patients (M:F = 22:8, mean 10.8 ± 3.1 years old) were included and four had tumours on abdominal MRI. ICC values were 0.906-0.995 between conventional and synthetic DWI and ADC with b = 1,500 s/mm2 in the liver, spleen and muscle. For mass lesions, ICC values were 0.997-0.999 for both synthetic DWI and ADC images. CONCLUSIONS: Synthetic DWI and ADC values obtained using a high b-value showed excellent agreement with conventional DWI for the liver, spleen, muscle, and mass in paediatric MRI.
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Imagem de Difusão por Ressonância Magnética , Neoplasias , Humanos , Criança , Adulto Jovem , Adulto , Adolescente , Estudos Retrospectivos , Reprodutibilidade dos Testes , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
Background: The rotational thromboelastogram (ROTEM) has been used in the management of massive bleeding and transfusion strategy. This study investigated ROTEM parameters measured during Cesarean section as predictors for the progression of persistent postpartum hemorrhage (PPH) in parturients with placenta previa. Methods: This prospective observational study recruited 100 women scheduled for elective Cesarean section after being diagnosed with placenta previa. Recruited women were divided into two groups according to the amount of estimated blood loss: the PPH group (PPH > 1500 ml) vs. the non-PPH group. ROTEM with laboratory tests was performed three times, preoperative, intraoperative, and postoperative time, which were compared between the two groups. Results: The PPH and non-PPH groups included 57 and 41 women, respectively. The area under the receiver-operating characteristic curve of postoperative FIBTEM A5 to detect PPH was 0.76 (95% CI = 0.64 to 0.87; P < 0.001). When postoperative FIBTEM A5 was 9.5, the sensitivity and specificity were 0.74 (95% CI = 0.55 to 0.88) and 0.73 (95% CI = 0.57 to 0.86), respectively. When subgrouping the PPH group based on the postoperative FIBTEM A5 value of 9.5, intraoperative cEBL was similar between the two subgroups; however, postoperative RBC was transfused more in the subgroup with FIBTEM A5 < 9.5 than the subgroup with FIBTEM A5 ≥ 9.5 (7.4 ± 3.0 vs 5.1 ± 2.3 units, respectively; P = 0.003). Conclusion: Postoperative FIBTEM A5, with appropriate selection of the cut-off value, can be a biomarker for more prolonged PPH and massive transfusion following Cesarean section by placenta previa.
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BACKGROUND: Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR). PATIENTS AND METHODS: This phase I/II study (NCT03052933) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase-α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1000 mg/m2 on days 1 and 8) in 28-day cycles. RESULTS: Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase II evaluation. Twenty-five patients were enrolled in phase II of the study. Frequent grade ≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival was 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma than those with PTCL-not otherwise specified (55.6% versus 15.4%, respectively, P = 0.074) and progression-free survival was significantly longer (13.0 versus 5.1 months, respectively, P = 0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders. CONCLUSION: The combination of copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients.
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Linfoma de Células T Periférico , Desoxicitidina/análogos & derivados , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Pirimidinas , Quinazolinas , Resultado do Tratamento , GencitabinaRESUMO
In vivo T-cell depletion using anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis of GvHD. We investigated the influence of thymoglobulin dose (an ATG) on GvHD following matched sibling donor (MSD) HSCT with a busulfan and fludarabine preparative regimen. Medical records of 180 patients who received MSD HSCT with a conditioning regimen of busulfan, fludarabine, and ATG (BuFluATG) were reviewed retrospectively. The median age was 53 years (range 18-68). Initial diagnoses were acute myeloid leukemia (73.3%) and myelodysplastic syndrome (26.7%). Forty-four and 68 patients (24.4 and 37.7%) experienced acute and chronic GvHD of any grade, respectively. High-dose (⩾4.5 mg/kg) ATG was independently associated with decreased risk of acute GvHD (hazard ratio=0.36, 95% confidence interval (CI): 0.15-0.84, P=0.019) compared to low-dose ATG (<4.5 mg/kg). Although ATG dose was associated with the risk of acute GvHD, it was not associated with the risk of chronic GvHD in our study. A higher dose (⩾4.5 mg/kg) of ATG decreases the risk of acute GvHD but had no significant impact on disease-free survival in MSD HSCT patients conditioned with BuFluATG. The optimal dose of ATG should be further investigated in a large prospective study context.
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Soro Antilinfocitário/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Idoso , Soro Antilinfocitário/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bussulfano/farmacologia , Feminino , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vidarabina/farmacologia , Vidarabina/uso terapêutico , Adulto JovemRESUMO
Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/radioterapia , Adolescente , Adulto , Idoso de 80 Anos ou mais , Quimiorradioterapia , Estudos de Coortes , Esquema de Medicação , Feminino , Humanos , Linfoma Extranodal de Células T-NK/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Adulto JovemRESUMO
Background/Objectives Neutrophilic dermatoses can be associated with autoimmune connective tissue diseases such as systemic lupus erythematosus (SLE). We analyzed clinical and histological features of neutrophilic urticarial dermatosis (NUD) and Sweet-like neutrophilic dermatosis (SLND)-the most recently delineated entities of the neutrophilic dermatoses. Methods We retrieved database medical records of patients with SLE whose skin biopsy demonstrated a neutrophilic-predominant infiltrate of the skin, and included those whose biopsies revealed findings of SLND or NUD. Results SLND skin lesions lasted longer than those of NUD and were localized to sun-exposed areas. All NUD cases resolved within one week either spontaneously or with treatment such as antihistamines, but SLND skin lesions lasted longer than one week; prednisone was used in four of these five patients. All NUD cases were found in existing SLE patients and were not associated with systemic signs of flare-up of SLE. However, 80% of SLND cases experienced flare-up of SLE; and in 60%, SLND developed concomitantly with SLE as a presenting sign. Conclusion Different clinical courses and relationships with SLE suggest that NUD and SLND have different pathogeneses for neutrophilic inflammatory reactions.
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Lúpus Eritematoso Sistêmico/diagnóstico , Neutrófilos/imunologia , Dermatopatias/diagnóstico , Pele/imunologia , Síndrome de Sweet/diagnóstico , Urticária/diagnóstico , Adulto , Biópsia , Bases de Dados Factuais , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Pele/efeitos dos fármacos , Pele/patologia , Dermatopatias/tratamento farmacológico , Dermatopatias/imunologia , Síndrome de Sweet/imunologia , Fatores de Tempo , Resultado do Tratamento , Urticária/tratamento farmacológico , Urticária/imunologia , Adulto JovemRESUMO
AIMS: To investigate whether preoperative magnetic resonance imaging (MRI) in patients with primary breast cancer is predictive of disease-free (DFS) and overall survival and to determine the prognostic factors indicating survival. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. From 2009 to 2010, 828 women with primary breast cancer and preoperative MRI were matched with 1613 women without such imaging. Patients were matched with regards to 25 patient and tumour-related covariates. A Cox proportional hazards model was used to investigate the time to recurrence and to estimate the hazard ratio for preoperative MRI. Log-rank tests and Cox proportional hazards survival analysis were carried out on total recurrence DFS and overall survival in the unmatched datasets. RESULTS: In total, 799 matched pairs were available for survival analysis. The MRI group showed a tendency towards better survival outcome; however, there were no significant differences in DFS and overall survival. Age at diagnosis (DFS hazard ratio = 0.98; overall survival hazard ratio = 1.04), larger tumour size (DFS hazard ratio = 1.01; overall survival hazard ratio = 1.02), triple negative breast cancer (DFS hazard ratio = 2.64; overall survival hazard ratio = 3.44) and the presence of lymphovascular invasion (DFS hazard ratio = 2.12; overall survival hazard ratio = 2.70) were independent significant variables for worse DFS and overall survival. CONCLUSION: Preoperative MRI did not result in an improvement in a patient's outcome. Age at diagnosis, tumour size, molecular subtype and lymphovascular invasion were significant independent factors affecting both DFS and overall survival.
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Neoplasias da Mama/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaAssuntos
Aeromonas hydrophila/virologia , Bacteriófagos/isolamento & purificação , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Peixe-Zebra , Animais , Bacteriófagos/classificação , Bacteriófagos/genética , Doenças dos Peixes/prevenção & controle , Genoma Viral , Infecções por Bactérias Gram-Negativas/prevenção & controleRESUMO
OBJECTIVE: To determine the factors associated with rhinostomy shape after endoscopic dacryocystorhinostomy (DCR) in patients with primary acquired nasolacrimal duct obstruction. DESIGN: Retrospective comparative study. SETTING: University hospital. PARTICIPANTS: One hundred and two cases in 70 patients were included in the study. MAIN OUTCOME MEASURE: All cases were classified into three groups according to the healed appearance of the rhinostomy: flat, ladle and ice scoop type. The flat shape was characterised by an opening with a flat surrounding and no clear border between the lacrimal sac and the nasal mucosa. The ladle shape had a depressed base without markings of a lacrimal sac. The ice scoop shape had a depressed base with a clear border between the lacrimal sac and the nasal mucosa. Anatomic success was defined as patency with syringing and endoscopic evidence of ostial patency. Functional success was defined as visualisation of fluorescein dye at the ostium and relief from epiphora. Clinical information and intra- and postoperative endoscopic video findings were compared between the three groups. RESULTS: Of the 102 cases, 19 flat, 37 ladle and 46 ice scoop type rhinostomies were observed during the follow-up examinations. Among the variables studied, patient demographics and rhinostomy size and location did not differ between the three groups. However, intraoperative lacrimal sac findings (sac size, wall thickness and mobility), postoperative ostial shrinkage and rhinostomy movement were associated with postoperative rhinostomy shape (all P < 0.05). With regard to surgical outcomes, there were no differences in anatomical patency between the three groups. However, the flat group had a worse functional success rate (73.7%) than the ladle (91.9%) and ice scoop (97.8%) groups (P = 0.008). A higher degree of ostial shrinkage and poor rhinostomy movement was observed with the flat shape appearance, which had a small, thick and poorly mobile lacrimal sac. CONCLUSIONS: Lacrimal sac characteristics play a prominent role in determining rhinostomy shape after endoscopic DCR. The rhinostomy shape, along with the degree of ostial shrinkage and rhinostomy movement, is predictive of functional success after endoscopic DCR.
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Dacriocistorinostomia/métodos , Obstrução dos Ductos Lacrimais/diagnóstico , Ducto Nasolacrimal/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal , Ducto Nasolacrimal/diagnóstico por imagem , Período Pós-Operatório , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Essentials Recombinant factor VIII BAY 94-9027 conjugates in a site-specific manner with polyethylene glycol. BAY 94-9027 was given to patients with severe hemophilia A as prophylaxis and to treat bleeds. BAY 94-9027 prevented bleeds at dose intervals up to every 7 days and effectively treated bleeds. BAY 94-9027 treatment was mainly well tolerated and no patient developed factor VIII inhibitors. Click to hear Dr Tiede's perspective on half-life extended factor VIII for the treatment of hemophilia A SUMMARY: Background BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) that conjugates in a site-specific manner with polyethylene glycol. Objective Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A. Patients/methods In this multinational, phase 2/3, partially randomized, open-label trial, men aged 12-65 years with FVIII < 1% and ≥ 150 exposure days to FVIII received BAY 94-9027 for 36 weeks on demand or prophylactically at intervals determined following a 10-week run-in period on 25 IU kg-1 body weight two times per week. Patients with > 1 bleed during the run-in subsequently received 30-40 IU kg-1 two times per week; patients with ≤ 1 bleed were eligible for randomization to every-5-days (45-60 IU kg-1 ) or every-7-days (60 IU kg-1 ) prophylaxis (1 : 1) for 26 additional weeks until randomization arms were filled. Patients who were eligible but not randomized continued twice-weekly prophylaxis. The primary efficacy outcome was annualized bleeding rate (ABR). Results The intent-to-treat population included 132 patients (prophylaxis, n = 112; on demand, n = 20). Median ABR (quartile [Q1; Q3]) for patients treated two times per week who were not eligible for randomization (n = 13) improved after dose increase (17.4 [14.3; 26.0] to 4.1 [2.0; 10.6]). Median ABR for patients randomized to every-5-days treatment (n = 43) was 1.9 (0; 4.2), similar to patients eligible for randomization but who continued treatment two times per week (n = 11). Median ABR for 32/43 patients (74%) who continued every-7-days prophylaxis until study end was 0.96 (0.0; 4.3). Six hundred and thirty-six of 702 bleeds (90.6%) were controlled with ≤ 2 infusions. No patient developed a FVIII inhibitor. Conclusions BAY 94-9027 prevented bleeding across three individually tailored dose regimens and was effective for treatment of bleeds.
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Fator VIII/farmacologia , Hemofilia A/tratamento farmacológico , Hemorragia/tratamento farmacológico , Polietilenoglicóis/farmacologia , Adolescente , Adulto , Idoso , Peso Corporal , Criança , Esquema de Medicação , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Domínios Proteicos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To compare the image quality between conventional volume interpolated breath-hold examination (VIBE) and radial VIBE in contrast-enhanced fat-suppressed T1-weighted images of paediatric abdominal magnetic resonance imaging (MRI) during free-breathing. MATERIALS AND METHODS: Images from paediatric patients who underwent contrast-enhanced abdominal MRI with a 3 T magnet using conventional VIBE (conventional group) and radial VIBE (radial group) while freely breathing were reviewed retrospectively. For objective analysis, the mean values of noise and signal-to-noise ratio (SNR) in the liver on contrast-enhanced fat-suppressed T1-weighted images were compared. For subjective analysis, overall image quality, respiratory motion, portal vein clarity, and hepatic margin sharpness were assessed using four-point scales. RESULTS: Nine patients (mean age of 2.8±2.3 years) in the conventional and 17 patients (mean age of 2.4±2.8 years) in the radial groups were included. According to the objective analysis, the noise was significantly lower and the SNR was significantly higher in the radial group than those in the conventional group (all, p<0.001). In the subjective analysis, overall image quality, respiratory motion, portal vein clarity, and hepatic margin sharpness were all significantly higher in the radial group (all, p<0.001). CONCLUSION: Paediatric abdominal MRI images with radial VIBE showed lower noise with higher SNR in objective analysis and higher image quality in subjective analysis, compared to conventional VIBE.
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Abdome/diagnóstico por imagem , Suspensão da Respiração , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Artefatos , Criança , Pré-Escolar , Meios de Contraste , Feminino , Humanos , Aumento da Imagem/métodos , Lactente , Masculino , Reprodutibilidade dos Testes , Respiração , Estudos Retrospectivos , Razão Sinal-RuídoRESUMO
BACKGROUND: We evaluated the effect of magnesium sulphate on increased pain in 44 patients undergoing staged bilateral total knee arthroplasty (TKA). METHODS: The magnesium group (n=22) and the control group (n=22) received magnesium sulphate and isotonic saline, respectively, throughout the surgery. Postoperative pain (visual analogue scale, VAS) at rest and the amounts of patient-controlled analgesia (PCA, fentanyl) and rescue analgesia (ketoprofen) administered during the first 48 h were compared between the two groups and within each group between the first and second TKA. RESULTS: The VAS scores were significantly higher in the control group than in the magnesium group not only after the first TKA [29 (11) vs 19 (9) at 24 h and 33 (8) vs 24 (10) at 48 h; P=0.001] but also after the second TKA [44 (17) vs 20 (10) at 24 h and 43 (14) vs 25 (10) at 48 h; P<0.001]. In the control group, VAS scores were significantly higher for the second than for the first operated knee [44 (17) vs 29 (11) at 24 h and 43 (14) vs 33 (8) at 48 h; P<0.001 and P=0.006, respectively]. In the magnesium group, there were no significant differences in VAS scores between the first and second TKA. Magnesium significantly reduced the amounts of rescue analgesics and fentanyl administered over the first 48 h postoperatively. CONCLUSIONS: Magnesium sulphate administration significantly reduced postoperative pain and minimized the difference in pain intensity between the first and second operations. CLINICAL TRIAL REGISTRATION: KCT0001361.
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Dor Aguda/tratamento farmacológico , Artroplastia do Joelho , Sulfato de Magnésio/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escala Visual AnalógicaRESUMO
We evaluated changes in rotational thromboelastometry (ROTEM(®) ) parameters and clinical outcomes in patients undergoing total hip replacement arthroplasty, with concomitant infusions of tranexamic acid and of 6% hydroxyethyl starch 130/0.4. Fifty-five patients were randomly assigned to either the tranexamic acid (n = 29) or the control (n = 26) group. Hydroxyethyl starch was administered in the range of 10-15 ml.kg(-1) during the operation in both groups. In the control group, the clot formation time and maximum clot firmness of APTEM showed significant differences when compared with those of EXTEM at one hour postoperatively, suggestive of fibrinolysis. In the tranexamic acid group, there was no significant difference between each postoperative EXTEM and APTEM parameter. In the tranexamic acid and control group, postoperative blood loss was 308 ml (210-420 [106-745]) and 488 ml (375-620 [170-910], p = 0.002), respectively, and total blood loss was 1168 ml (922-1470 [663-2107]) and 1563 ml (1276-1708 [887-1494], p = 0.003). Haemoglobin concentration was higher in the tranexamic acid group on the second postoperative day (10.5 (9.4-12.1 [7.9-14.0]) vs. 9.6 (8.9-10.5[7.3-16.0]) g.dl(-1) , p = 0.027). In patients undergoing total hip replacement arthroplasty, postoperative fibrinolysis aggravated by hydroxyethyl starch was attenuated by co-administration of 10 mg.kg(-1) tranexamic acid, which may have led to less postoperative blood loss.
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Antifibrinolíticos/farmacologia , Artroplastia de Quadril , Coagulação Sanguínea/efeitos dos fármacos , Tromboelastografia/métodos , Ácido Tranexâmico/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Tranexâmico/efeitos adversosRESUMO
The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.
Assuntos
Transformação Celular Neoplásica/genética , Proteína Forkhead Box M1/genética , Fígado/metabolismo , Peroxirredoxinas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Knockout , Camundongos Nus , Camundongos Transgênicos , Células NIH 3T3 , Peptídeos/farmacologia , Peroxirredoxinas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transplante HeterólogoRESUMO
Monosomal karyotype (MK) defined by either ⩾2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated.
Assuntos
Leucemia Mieloide Aguda/genética , Monossomia/genética , Monossomia/patologia , Cariótipo Anormal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Povo Asiático , Terapia Combinada , Análise Citogenética , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Adulto JovemRESUMO
BACKGROUND: Limited research has been conducted on the association between intake of fruits and vegetables and hypertriglyceridemia, especially in Asian populations. This study aimed to investigate the association between total fruit and vegetable intake, as well as subgroups of fruit and vegetable intake, with hypertriglyceridemia among Korean adults. METHODS: We conducted a cross-sectional study of 7934 adults aged 19-64 years from the fourth Korean Health and Nutrition Examination Survey. Fruit and vegetable intake was estimated from a food frequency questionnaire. Subgroups of fruits and vegetables included citrus, non-citrus and carotene-rich fruits and cruciferous, green leafy and carotene-rich vegetables. Hypertriglyceridemia (plasma triglyceride ⩾150 mg/dl) was diagnosed using a blood sample drawn after 12+ hours of fasting. RESULTS: There were 2001 (25.2%) cases of hypertriglyceridemia among the participants. Total fruit intake was significantly inversely associated with the prevalence of hypertriglyceridemia; the multivariate odds ratios (95% confidence intervals) of hypertriglyceridemia across increasing quintiles were 1.00 (ref), 0.76 (0.62, 0.92), 0.72 (0.58, 0.90), 0.68 (0.54, 0.85) and 0.64 (0.49, 0.82; Ptrend=0.001) after controlling for survey year, body mass index, waist circumference, smoking, alcohol drinking, physical activity, education and income. Similar inverse associations were found for all fruit subgroups. However, we found no significant association between intakes of total or subgroups of vegetable and hypertriglyceridemia; the odds ratio for top vs bottom quintile was 1.00 (0.81-1.24) for total vegetable intake. CONCLUSIONS: Our findings support a potential beneficial role of fruit consumption to reduce blood triglyceride levels in Asian populations.