METHODS: This was a two-centre randomised controlled trial of CI versus IB dosing of beta-lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post-randomisation, 14- and 30-day survival, and time to white cell count normalisation.
RESULTS: A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p MIC than the IB arm on day 1 (97 versus 70 %, p
MATERIALS & METHODS: This is a case-control study consisting of 47 MDD patients and 47 healthy controls. MDD patients were treated with antidepressant drugs according to their physician's choice. The severity of MDD was assessed using Beck Depression Inventory (BDI) and Montgomery-Asberg Depression Rating Scale (MADRS) at the time of recruitment. Healthy controls completed the Depression Anxiety Scoring System (DASS21) questionnaire to ensure they were in good mental health without history of MDD. The percentage and absolute count of CD4+ CD25+ Tregs and CD4+ CD25+ FOXP3+ Tregs were identified by multiparameter flow cytometry.
RESULTS: The percentage and absolute count of CD4+ CD25+ Treg cells were significantly higher in MDD patients than in healthy controls (P<0.001, in both cases). Likewise, the percentage and absolute count of CD4+ CD25+ FOXP3+ Treg cells were also significantly higher in MDD patients compared to healthy controls (P=0.003 and P=0.002, respectively). However, there was no significant correlation between the percentage and absolute count of CD4+ CD25+ Treg and CD4+ CD25+ FOXP3+ Treg cells with BDI or MADRS score.
CONCLUSIONS: Our results suggest that antidepressant treatments contributed to an upregulation of Tregs in MDD patients.
METHODS AND RESULTS: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared to normal germinal centre B (GCB) cells, were expressed more highly in the activated B cell-like DLBCL (ABC-DLBCL) subtype and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL cases (P < 0.05). Our immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly with more aggressive clinical parameters, including higher lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) scores or stage (P < 0.01 for each of the parameters) and the ABC-DLBCL subtype (P = 0.016). TRPM4 positivity conferred significantly worse OS (P = 0.004) and progression-free survival (PFS) (P = 0.005). Worse OS remained associated significantly with TRPM4 positivity in multivariate analysis, including higher International Prognostic Index (IPI) or the non-GCB DLBCL phenotype (P < 0.05).
CONCLUSIONS: TRPM4 protein expression is up-regulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patient outcomes.
MATERIALS AND METHODS: A comparative cross-sectional study involving 98 RA patients was conducted at Hospital Universiti Sains Malaysia, Kubang Kerian, Malaysia. Clinical oral examination was carried out to determine the CP status of RA patients. RF, ACPA and erythrocyte sedimentation rate (ESR) were measured, and the 28-joint Disease Activity Score (DAS-28) was assessed.
RESULTS: Forty-five patients (45.9%) were found to have CP (95% CI: 0.36-0.56). No significant difference was observed in the prevalence of positive RF (p=0.989) or ACPA (p=0.431) in CP and non-CP RA patients. There was also no significant association between active RA disease (DAS-28 score ≥3.2) and RF positivity in CP (p=0.927) and non-CP (p=0.431) RA patients as well as ACPA positivity in CP (p=0.780) and non-CP (p=0.611) RA patients.
CONCLUSION: In our cohort of RA patients, we did not find significant associations between elevated RF, ACPA, or active RA disease with the presence of CP. There were also no significant associations between elevated RF or ACPA with active RA disease.
MATERIALS AND METHODS: A prospective cohort study over one-year duration was conducted from December, 2014 until December, 2015, involving 237 women who presented with abnormal vaginal discharge, preterm labour or preterm prelabour rupture of membrane between 22- and 34-weeks period of gestation. Vaginal swabs were sent for culture and sensitivity, BV® Blue testing and PCR for Gardnerella vaginalis (GV).
RESULTS: BV was diagnosed in 24/237 (10.1%) cases. The median gestational age was 31.6 weeks. GV was isolated from 16 out of 24 (66.7%) in the BV positive group. There was a significantly higher preterm birth rate, below 34 weeks (22.7% vs. 6.2%, p = 0.019) in women with BV. There was no statistically significant difference in maternal outcome such as clinical chorioamnionitis or endometritis. However, placental pathology revealed more than half (55.6%) of women with BV had histologic chorioamnionitis. Neonatal morbidity was significantly higher with exposure to BV, with a lower median birth weight, higher rate of neonatal intensive care unit admission (41.7% vs. 19.0%, p = 0.010), increased intubation for respiratory support (29.2% vs. 7.6%, p = 0.004) and respiratory distress syndrome (33.3% vs. 9.0%, p = 0.002).
CONCLUSION: More research is needed to formulate guidelines for prevention, early detection and treatment of BV during pregnancy to reduce intrauterine inflammation and the associated adverse fetal outcomes.
MATERIALS AND METHODS: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle- related transcripts was analysed based on a previous microarray dataset.
RESULTS: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of ERα protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied.
CONCLUSIONS: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.