Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation.

BACKGROUND: Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood. METHODS: We report a novel model to investigate the in vitro mineralisation potential of a panel of mammary cell lines. Primary mammary tumours were produced by implanting tumourigenic cells into the mammary fat pads of female BALB/c mice. RESULTS: Hydroxyapatite (HA) was deposited only by the tumourigenic cell lines, indicating mineralisation potential may be associated with cell phenotype in this in vitro model. We propose a mechanism for mammary mineralisation, which suggests that the balance between enhancers and inhibitors of physiological mineralisation are disrupted. Inhibition of alkaline phosphatase and phosphate transport prevented mineralisation, demonstrating that mineralisation is an active cell-mediated process. Hydroxyapatite was found to enhance in vitro tumour cell migration, while calcium oxalate had no effect, highlighting potential consequences of calcium deposition. In addition, HA was also deposited in primary mammary tumours produced by implanting the tumourigenic cells into the mammary fat pads of female BALB/c mice. CONCLUSION: This work indicates that formation of mammary HA is a cell-specific regulated process, which creates an osteomimetic niche potentially enhancing breast tumour progression. Our findings point to the cells mineralisation potential and the microenvironment regulating it, as a significant feature of breast tumour development

ICAR: endoscopic skull‐base surgery

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Intravitreal Faricimab for Previously Treated Neovascular Age-Related Macular Degeneration

Abraham Hang, Taylor Ngo, Jaipreet Singh Virk, Kareem Moussa, Ala Moshiri, Parisa Emami-Naeini, Susanna S Park Department of Ophthalmology & Vision Science, University of California Davis Eye Center, Sacramento, CA, USACorrespondence: Susanna S Park, Department of Ophthalmology & Vision Science, University of California Davis Eye Center, Ernest E. Tschannen Eye Institute, 4860 Y Street, Sacramento, CA, 95817, USA, Tel +1-916-734-6080, Email [email protected]: To report our real-world experience using intravitreal faricimab, a novel anti-vascular endothelial growth factor (anti-VEGF) therapy, in eyes with neovascular age-related macular degeneration (nAMD) previously treated with other anti-VEGF therapy.Patients and Methods: A retrospective, single-center study of previously treated nAMD eyes treated with faricimab.Results: In 88 eyes (73 patients), mean baseline best-corrected visual acuity (BCVA) was 20/63 (range 20/20 to CF) with mean anti-VEGF injection interval of 6.1+ 2.0 weeks. Mean baseline central subfield thickness (CST) was 291+ 73 μm. During mean follow-up of 30.1+ 13.5 (range 7.0 to 50.3) weeks on faricimab, the eyes received an average of 5.1+ 2.4 injections (range 1 to 11). Mean BCVA remained at 20/63 (p=0.11), but injection interval increased to 7.4+ 2.6 weeks (p< 0.001), and CST decreased to 262+ 63 μm (p< 0.001). Multiple linear regression analysis revealed that higher number of different anti-VEGF drugs used at baseline was associated with a lower decrease in CST on faricimab (p=0.04) while total number of anti-VEGF injections at baseline (p=0.56) and time on faricimab (p=0.68) were not associated. Faricimab was discontinued in 23 eyes (26.1%), including 8 eyes for poor response, 2 eyes for persistent new floaters and 4 eyes for new vision decrease which reversed after stopping faricimab.Conclusion: In previously treated nAMD eyes, intravitreal faricimab was associated with increased mean treatment interval and decreased CST but no improvement in mean BCVA. The benefit of faricimab on CST reduction may be diminished in eyes previously treated with multiple different types of anti-VEGF therapy.Keywords: anti-VEGF therapy, intravitreal therapy, real-world experience, central subfield thickness, optical coherence tomograph

Patterns of illness in travelers visiting Mexico and Central America: the GeoSentinel experience

BACKGROUND: Mexico and Central America are important travel destinations for North American and European travelers. There is limited information on regional differences in travel related morbidity. METHODS: We describe the morbidity among 4779 ill travelers returned from Mexico and Central America who were evaluated at GeoSentinel network clinics during December 1996 to February 2010. RESULTS: The most frequent presenting syndromes included acute and chronic diarrhea, dermatologic diseases, febrile systemic illness, and respiratory disease. A higher proportion of ill travelers from the United States had acute diarrhea, compared with their Canadian and European counterparts (odds ratio, 1.9; P < .0001). During the 2009 H1N1 influenza outbreak from March 2009 through February 2010, the proportionate morbidity (PM) associated with respiratory illnesses in ill travelers increased among those returned from Mexico, compared with prior years (196.0 cases per 1000 ill returned travelers vs 53.7 cases per 1000 ill returned travelers; P < .0001); the PM remained constant in the rest of Central America (57.3 cases per 1000 ill returned travelers). We identified 50 travelers returned from Mexico and Central America who developed influenza, including infection due to 2009 H1N1 strains and influenza-like illness. The overall risk of malaria was low; only 4 cases of malaria were acquired in Mexico (PM, 2.2 cases per 1000 ill returned travelers) in 13 years, compared with 18 from Honduras (PM, 79.6 cases per 1000 ill returned travelers) and 14 from Guatemala (PM, 34.4 cases per 1000 ill returned travelers) during the same period. Plasmodium vivax malaria was the most frequent malaria diagnosis. CONCLUSIONS: Travel medicine practitioners advising and treating travelers visiting these regions should dedicate special attention to vaccine-preventable illnesses and should consider the uncommon occurrence of acute hepatitis A, leptospirosis, neurocysticercosis, acute Chagas disease, onchocerciasis, mucocutaneous leishmaniasis, neurocysticercosis, HIV, malaria, and brucellosis