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Clinical trials have shown that the addition of pertuzumab to trastuzumab-based chemotherapy for first-line treatment of ERBB2-positive metastatic breast cancer is associated with considerable improvement in overall survival (OS). In the second-line setting, trastuzumab emtansine (T-DM1) improves OS compared with capecitabine/lapatinib in patients previously treated with trastuzumab-based chemotherapy. However, there are few data describing long-term real-world outcomes with these agents.

To describe practice patterns and outcomes associated with pertuzumab and T-DM1 in routine clinical practice.

This population-based retrospective cohort study used the Ontario Cancer Registry linked to electronic treatment databases to identify all patients treated with pertuzumab and T-DM1 following reimbursement approval in Ontario, Canada, which has a single-payer public health system. click here Participants included women with stage IV ERBB2-positive metastatic breast cancer receiving treatment with pertuzumab for first-linets with prior pertuzumab treatment than in the pertuzumab-naive subgroup (12 vs 19 months; adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = .004).

In this population-based cohort study, the survival of patients treated with pertuzumab and T-DM1 in routine practice appeared inferior to results from pivotal clinical trials. Differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice. Further work is needed to understand the effectiveness of T-DM1 after pertuzumab exposure.

In this population-based cohort study, the survival of patients treated with pertuzumab and T-DM1 in routine practice appeared inferior to results from pivotal clinical trials. Differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice. Further work is needed to understand the effectiveness of T-DM1 after pertuzumab exposure.

To investigate the temporal characteristics of visual processing at the fovea and the periphery in high myopia.

Eighteen low (LM, ≤ -0.50 and > -6.00 D) and 18 high myopic (HM, ≤ -6.00 D) participants took part in this study. The contrast thresholds in an orientation discrimination task under various stimulus onset asynchrony (SOA) masking conditions were measured at the fovea and a more peripheral area (7°) for the two groups. An elaborated perceptual template model (ePTM) was fit to the behavioral data for each participant.

An analysis of variance with three factors (SOA, degree of myopia and eccentricity) was performed on the threshold data. The interaction between SOA and degree of myopia in the fovea was significant (F (4, 128) = 2.66, P = 0.036), suggesting that the masking effect had different temporal patterns between the two groups. The temporal profiles for the two groups were derived based on the ePTM model. The peak and the spread of the temporal window in the fovea were much lower and wider, respectively, in the HM group than that in the LM group (both Ps < 0.05). There was no significant difference in the peripheral temporal window between the two groups.

High myopia is associated with defective temporal processing in the fovea, captured by a flattened temporal window.

High myopia is associated with defective temporal processing in the fovea, captured by a flattened temporal window.

To determine the role of scavenger receptor expressed by endothelial cell-1 (SREC-Ⅰ) in vitro and in a mouse model of Aspergillus fumigatus keratitis.

SREC-Ⅰ mRNA and protein expression were tested in both normal and A fumigatus stimulated human corneal epithelial cells (HCECs). Immunofluorescence was used to detect SREC-Ⅰ expression in human corneas with or without A fumigatus infection. HCECs were incubated with SREC-Ⅰ small interfering RNA, then the mRNA levels of LOX-1, IL-1β, and TNF-α were detected after A fumigatus stimulation. A mouse fungal keratitis (FK) model was established and SREC-Ⅰ mRNA and protein expression were detected by RT-PCR, Western blot and immunofluorescence. The severity of FK was evaluated by clinical score. CLCX1, LOX-1, IL-1β, and TNF-α mRNA expression levels were tested before and after anti-SREC-Ⅰ treatment.

SREC-Ⅰ expressed in normal and A fumigatus treated HCECs and human corneal epithelium. In vitro experiment showed that SREC-Ⅰ mRNA and protein levels were significantly increased after A fumigatus stimulation. SREC-Ⅰ small interfering RNA treatment inhibited the expressions of LOX-1, IL-1β, and TNF-α in HCECs. The expressions of CLCX1, LOX-1, IL-1β, and TNF-α were elevated in mice with A fumigatus keratitis, which could be decreased by SREC-Ⅰ-neutralizing antibody treatment.

SREC-Ⅰ is a key mediator in inflammatory response induced by A fumigatus keratitis. SREC-Ⅰ blockade could be a potential therapeutic approach for FK.

SREC-Ⅰ is a key mediator in inflammatory response induced by A fumigatus keratitis. SREC-Ⅰ blockade could be a potential therapeutic approach for FK.

To investigate the association between precorneal tear film (PCTF)- and meibum-derived (O-Acyl)-omega-hydroxy fatty acids (OAHFAs) and PCTF thinning in meibomian gland health and dysfunction.

Of 195 eligible subjects (18-84 years, 62.6% female), 178 and 170 subjects provided both PCTF optical coherence tomography (OCT) imaging and mass spectrometry data for tears (n = 178) and meibum (n = 170). The PCTF thinning rate was measured in the right eye using an ultra-high-resolution, custom-built OCT. Tear and meibum samples from the right eye were infused into the SCIEX 5600 TripleTOF mass spectrometer in the negative ion mode. Intensities (m/z) of preidentified OAHFAs were measured with Analyst 1.7TF and LipidView 1.3 (SCIEX). Principal component (PC) analyses and Spearman's correlations (ρ) were performed to evaluate the association between OAHFAs and PCTF thinning rates.

In meibum and tear samples, 76 and 78 unique OAHFAs were detected, respectively. The first PC scores of the meibum-derived OAHFAs had sthe stabilization and thinning of the PCTF. The tear-film derived OAHFAs were, however, independent of the rate of PCTF thinning.