Association of LDL-cholesterol <1.8 mmol/L and statin use with the recurrence of intracerebral hemorrhage.

BACKGROUND: Recent intensive low-density lipoprotein cholesterol (LDL-C) lowering trials, including FOURIER, ODYSSEY OUTCOMES, and Treat Stroke to Target (TST) trials, have mostly refuted the concern surrounding statin use, LDL-C lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than 10 times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking. AIMS: We aim to investigate the association between LDL-C levels and statin use with ICH risk among ICH survivors, and to determine whether the risk differed with patients' characteristics, especially ICH etiology. METHODS: Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ⩾1.8 mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models. RESULTS: In 502 ICH survivors (mean age = 64.2 ± 13.5 years, mean follow-up LDL-C = 2.2 ± 0.6 mmol/L, 28% with LDL-C <1.8 mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9 ± 2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio (AHR) = 1.07, 95% confidence interval (CI) = 0.57-2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8 mmol/L (AHR = 1.99, 95% CI = 1.06-3.73). This association was predominantly observed in ICH attributable to CAA (AHR = 2.52, 95% CI = 1.06-5.99) and non-statin users (AHR = 2.91, 95% CI = 1.08-7.86). CONCLUSION: The association between post-ICH LDL-C <1.8 mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.

Targeting proteoglycan receptor PTPσ restores sensory function after spinal cord dorsal root injury by activation of Erks/CREB signaling pathway.

Dorsal root injury commonly results in irreversible loss of sensory functions because of the limited intrinsic regenerative capacity of adult sensory axons and the growth-inhibitory environment at the dorsal root entry zone (DREZ) between the dorsal root and the spinal cord. Chondroitin sulfate proteoglycans (CSPGs) are the dominant suppressors of axonal regeneration, acting via neuronal receptors including protein tyrosine phosphatase-σ (PTPσ). ISP (Intracellular Sigma Peptide) is a small peptide mimetic of the PTPσ wedge region that has been developed to target PTPσ and relieve CSPG inhibition. Extracellular regulated kinases (Erks) and cAMP response element binding protein (CREB) are signaling molecules downstream of CSPGs and PTPσ; they are expressed in neurons and essential for axon growth. In this study, we observed that ISP administration could promote sensory function restoration in adult rats after dorsal spinal root crush injury. Our results show that systemic ISP administration would not only significantly increase sensory axon regeneration and functional recovery, but also activate Erk and CREB signaling pathway. Furthermore, ISP has also been verified to increase dorsal root ganglion axonal remyelination in vitro. These results suggest that modulation of PTPσ by ISP represents a promising therapeutic strategy for sensory neuronal injuries.

Malpractice litigation in acute stroke care - where are we now?

Acute stroke care has undergone momentous changes in recent years with the introduction of intravenous thrombolysis, mechanical thrombectomy and integrated stroke services. While these are welcome developments, they also carry unique medico-legal challenges. In 2015, a patient from Greater Manchester was awarded over £1 million in compensation after ambulance paramedics failed to admit her to a specialist unit. This paper explores the medico-legal implications of this first but over looked thrombolysis-related claim in the United Kingdom. It is submitted that the highly time-dependent and multidisciplinary nature of acute stroke care may expose a host of healthcare personnel, both medical and non-medical, to risks of legal pursuit for failing to provide appropriate care, and that available scientific evidence will likely support such claims. The situation calls for an urgent and concerted effort at implementing improvement measures at national levels. A reminder of the legal consequences of substandard acute stroke care is timely and necessary.

New Hong Kong statute protects factual statements in medical apologies from use in litigation.

Providing an apology which contains a factual explanation following a medical adverse incident may facilitate an amicable settlement and improve patient experience. Numerous apology laws exist with the aim of encouraging an apology but the lack of explicit and specific protection for factual admissions included in "full" apologies can give rise to legal disputes and deter their use. The new Hong Kong Apology Ordinance expressly prohibits the admission of a statement of fact in an apology as evidence of fault in a wide range of applicable proceedings and thus provides the clearest and most comprehensive apology protection to date. This should significantly encourage open medical disclosure and the provision of an apology when things go wrong. This paper examines the significance and implication of the Apology Ordinance in the medico-legal context.