Bmc Med
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Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood-brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets. ⋯ ADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.
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Duchenne muscular dystrophy (DMD) is a progressive, degenerative muscular disorder and cognitive dysfunction caused by mutations in the dystrophin gene. It is characterized by excess inflammatory responses in the muscle and repeated degeneration and regeneration cycles. Neutral sphingomyelinase 2/sphingomyelin phosphodiesterase 3 (nSMase2/Smpd3) hydrolyzes sphingomyelin in lipid rafts. This protein thus modulates inflammatory responses, cell survival or apoptosis pathways, and the secretion of extracellular vesicles in a Ca2+-dependent manner. However, its roles in dystrophic pathology have not yet been clarified. ⋯ nSMase2/Smpd3-modulated lipid raft integrity is a potential therapeutic target for DMD.
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Prosthetic joint infection (PJI) following total hip replacement (THR) surgery is a serious complication that negatively impacts patients' lives and is financially burdensome for healthcare providers. As the number of THRs increases, so does this financial burden. This research estimates the economic burden with respect to inpatient and day case hospital admissions for patients receiving revision surgery for PJI following primary THR. ⋯ In the 5 years following primary THR, patients who develop PJI and have revision surgery cost approximately £33,000 (over 5-fold) more than patients not revised for PJI based on their hospital inpatient and day case admissions alone. The total burden of PJI is likely to be much higher when also considering outpatient, primary and community care costs. This highlights the need to find both ways to reduce the incidence of PJI following THR and cost-effective treatment strategies if PJI occurs.
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Meta Analysis
Platelet activation in adult HIV-infected patients on antiretroviral therapy: a systematic review and meta-analysis.
Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The current evidence on platelet activation levels in patients with HIV remains inconclusive. We therefore aimed to systematically synthesise evidence on the association of platelet activation in HIV-infected patients on successful treatment. ⋯ The levels of platelet activation are elevated in treatment-naïve HIV-infected patients, and these persist during successful ART. Further studies should assess the clinical relevance of monitoring the levels of platelet activation in HIV-infected patients on ART.
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Historical Article
Socioeconomic inequalities in blood pressure: co-ordinated analysis of 147,775 participants from repeated birth cohort and cross-sectional datasets, 1989 to 2016.
High blood pressure (BP) is a key modifiable determinant of cardiovascular disease and a likely determinant of other adverse health outcomes. While socioeconomic inequalities in BP are well documented, it remains unclear (1) how these inequalities have changed across time, given improvements over time in the detection and treatment of high BP (hypertension); (2) whether BP inequalities are present below and above hypertension treatment thresholds; and (3) whether socioeconomic position (SEP) across life has cumulative effects on BP. We sought to address these gaps using evidence from two complementary sources: birth cohort and repeated cross-sectional datasets. ⋯ Socioeconomic inequalities in BP have persisted from 1989 to 2016 in Britain/England, despite improved detection and treatment of high BP. To achieve future reductions in BP inequalities, policies addressing the wider structural determinants of high BP levels are likely required, particularly those curtailing the obesogenic environment-targeting detection and treatment alone is unlikely to be sufficient.