Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

PURPOSE: A flow diverter (FD) is an effective treatment option for intracranial aneurysms. The Flow Re-direction Endoluminal Device (FRED) is a relatively new flow diverter with a unique dual-layer design. We report our experience and short-term results with the FRED. MATERIALS AND METHODS: We did a retrospective review of all consecutive cases in which the FRED was used to treat intracranial aneurysms at a single institution from March 2014 till December 2015. Clinical parameters, aneurysm characteristics, technical results and short-term outcomes were reviewed. RESULTS: Eleven intracranial aneurysms were treated with the FRED in 11 patients. The technical device deployment success rate was 100%. Immediate reduction in intra-aneurysmal flow after deployment was noted in 10 cases. The aneurysm occlusion rate at 6 months was 75%. There was 1 complication of in-stent thrombosis immediately after deployment. There was no side branch occlusion, delayed aneurysm rupture, stroke, or intraparenchymal haemorrhage. There was no neurological deficit, morbidity, or mortality. CONCLUSION: The FRED is a new FD. It has shown to be safe and effective in our series. The unique dual-layer design of the device renders it to have technical advantages over other FDs. The 6-month aneurysm occlusion rate and complication profile of FRED are similar to other FDs.
Aneurysm ; Follow-Up Studies* ; Humans ; Intracranial Aneurysm* ; Mortality ; Retrospective Studies ; Rupture ; Stents ; Stroke ; Thrombosis

BACKGROUNDSince Macao's return of sovereignty to China in December 1999, the life style of Macao residents has changed. The aim of this study was to investigate changes of death patterns in Macao residents from 1986 to 2006 in order to identify the trends and patterns of major public health problems, which could provide the guidance for developing public health policies.

METHODSA retrospective study was conducted for this investigation. Research data were collected from official websites and statistical yearbooks and classified by the International Classification of Diseases (ICD)-9.

RESULTSIt was observed that mortality from the three major causes of (1) infectious, maternal and childhood diseases, (2) chronic non-communicable diseases, and (3) injury and poisoning were 17.7, 298.2 and 26.0 per 100 000, respectively. The largest decrease in death rate over the 21-year study-period was from infectious, maternal and childhood diseases (62.5%). The highest mortality rate was ischemic heart diseases (37.0%). The largest increase in mortality rate was lung cancer (46.9%).

CONCLUSIONSMortality rate of Macao residents progressively decreased, but the constituent ratio of death from chronic non-communicable diseases was increasing. The mortality rate of lung cancer was clearly ascending, so emphasis should be put on tertiary prevention in future.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cause of Death ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Macau ; epidemiology ; Male ; Middle Aged ; Neoplasms ; mortality ; Primary Health Care ; Retrospective Studies ; Time Factors

Endogenous ribonucleotides(RNs)and deoxyribonucleotides(dRNs)are important metabolites related to the pathogenesis of many diseases.In light of their physiological and pathological significances,a novel and sensitive pre-column derivatization method with N-(t-butyldimethylsilyl)-N-methyltri-fluoroacetamide(MTBSTFA)was developed to determine RNs and dRNs in human cells using high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).A one-step extraction of cells with 85％methanol followed by a simple derivatization reaction within 5 min at room temper-ature contributed to shortened analysis time.The derivatives of 22 nucleoside mono-,di-and tri-phosphates were retained on the typical Cig column and eluted by ammonium acetate and acetonitrile in 9 min.Under these optimal conditions,good linearity was achieved in the tested calibration ranges.The lower limit of quantitation(LLOQ)was determined to be 0.1-0.4 μM for the tested RNs and 0.001-0.1 μM for dRNs.In addition,the precision(CV)was＜15％and the RSD of stability was lower than 10.4％.Furthermore,this method was applied to quantify the endogenous nucleotides in human colorectal carcinoma cell lines HCT116 exposed to 10-hydroxycamptothecin.In conclusion,our method has proven to be simple,rapid,sensitive,and reliable.It may be used for specific expanded studies on intracellular pharmacology in vitro.

Child ; Female ; Humans ; Male ; Mucopolysaccharidosis IV ; genetics ; Mutation ; N-Acetylgalactosamine-4-Sulfatase ; genetics

The terms "Surgery 1.0" to "Surgery 4.0" came from the term "Industry 4.0" . In 2011, the German Government at the Hannover Messe introduced the term "Industry 4.0" to describe the four stages of industrial developments: Industrial revolution, which happened in England in the 18th century, was considered as "Industry 1.0" . The beginning of "Industry 1.0" and the subsequent developments into "Industry 2.0" , "Industry 3.0" and "Industry 4.0" were all based on important scientific discoveries at those material time periods. In 2018, Hooshair A first introduced the concept of similar developments from "surgery 1.0" to "surgery 4.0" . Similar to industrial developments, these stages of surgical developments were based on important scientific discoveries, although the time periods of developments of these surgical stages were slightly different from those of the industrial developmental stages. "Surgery 4.0" started at the beginning of the 21st century. Its development is based on the scientific advances in big data, artificial intelligence, automation, modern robots and 5G technology. Within a short period of 20 years, each of these scientific discoveries has rapidly progressed. As each of these developments leads to increase in demand of another one, this leads to a virtuous cycle with rapid developments in all these individual scientific discoveries. Is there any room for further development of "Surgery 4.0" ? The authors predict that there will be a rapid development into "Surgery 5.0" by integrating these discoveries. Instead of individual and rapid development of each of the scientific advances, these advances will integrate into a single system with further fast and rapid growth. It is ambitions for the authors to make such a prediction when "Surgery 4.0" is still at an developmental stage. However the authors are confident that "surgery 5.0" will not only come, but it will come within a reasonably short time, as this is the natural development of science.

BACKGROUNDData of classical inborn errors of metabolism (IEM) of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.

METHODSThe laboratory records of plasma amino acids, plasma acylcarnitines and urine organic acids analyses from year 2005 to 2009 inclusive in three regional chemical pathology laboratories providing biochemical and genetic diagnostic services for IEM were retrospectively reviewed.

RESULTSAmong the cohort, 43 patients were diagnosed of IEM, including 30 cases (69%) of amino acidemias (predominantly citrin deficiency, hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency and tyrosinemia type I), 5 cases (12%) of organic acidemias (predominantly holocarboxylase synthetase deficiency) and 8 cases (19%) of fatty acid oxidation defects (predominantly carnitine-acylcarnitine translocase deficiency). The incidence of classical IEM in Hong Kong was roughly estimated to be at least 1 case per 4122 lives births, or 0.243 cases per 1000 live births. This incidence is similar to those reported worldwide, including the mainland of China. The estimated incidence of hyperphenylalaninemia was 1 in 29 542 live births.

CONCLUSIONSOur data indicate that it is indisputable for the introduction of expanded newborn screening program in Hong Kong. Since Hong Kong is a metropolitan city, a comprehensive expanded newborn screening program and referral system should be available to serve the neonates born in the area.

Acids ; urine ; Amino Acids ; blood ; Carnitine ; analogs & derivatives ; blood ; Hong Kong ; epidemiology ; Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; blood ; diagnosis ; epidemiology ; urine ; Neonatal Screening ; methods ; Tandem Mass Spectrometry

OBJECTIVETo investigate the efficacy of a herbal formula in the prevention of influenza or influenza-like syndrome among elderies residing in old-people's home in Hong Kong. The secondary objectives are to investigate the quality of life (QOL) and symptomology changes among the herbal users and to evaluate the safety of this formula.

METHODSIn ten old people's home or community centres in New Territories, Hong Kong, 740 eligible subjects agreed to join the study and were randomized to receive a herbal formula or a placebo on alternate days over 8 weeks. Among those 740 participants, 113 had provided blood samples for immunological assessments before and after the study drug. Assessments were done at 0, 4, 8 and 12 weeks. Participants were instructed to keep a daily record of body temperature and any symptoms as sore throat, myalgia, running nose or cough, and to report to assessor accordingly. Those reporting body temperature of 37.8 °C and above would be visited and a proper nasopharyngeal swab be taken for viral study.

RESULTSSeventy-two participants developed influenza-like-symptoms but none of them was proven influenza in their nasopharyngeal swabs, 40 of these patients belonged to the herbal group and 32 to the placebo group, without significant differences between groups. The difference on the changes in QOL between the two groups was not statistically significant. However, in the immunological study, the natural killer cell absolute count was significantly increased in the herbal group compared with the placebo group (463 ± 253 vs 413 ± 198, P<0.05).

CONCLUSIONSThe herbal preparation was not effective compared with placebo in the prevention of influenza-like syndrome. It was however safe and possibly supporting immunological responses.

Aged ; Demography ; Double-Blind Method ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Humans ; Immunologic Tests ; Influenza, Human ; drug therapy ; immunology ; prevention & control ; Male ; Quality of Life ; Vaccination

Objectives: Type 2 diabetes mellitus (T2DM) shares a complex relationship with bone metabolism and few studies investigated the effect of impaired bone health on the risk of T2DM. This study was conducted to investigate the association between hip fractures and the risk of incident T2DM. Methods: This is a retrospective cohort study using data from the real-world hip fracture cohort. Hong Kong Chinese patients aged ≥ 65 years without T2DM who were admitted to public hospitals due to a fall between 2008 and 2015 were included in the study. Patients who sustained falls with and without hip fractures were matched by propensity score (PS) at a 1:1 ratio. Competing risk regression was used to evaluate the association between hip fracture and incident T2DM, with death being the competing event. Results: A total of 23,314 hip fracture cases were matched to 23,314 controls. The median follow-up time was 5.09 years. The incidence rate of T2DM was 11.947 and 14.505 per 1000 person-years for the hip fracture and control group respectively. After accounting for the competing risk of death, the hip fracture group had a significantly lower risk of developing T2DM (HR: 0.771, 95% CI: 0.719–0.827). Similar results were observed in all subgroups after stratification by age and sex. Conclusions Hip fracture was found to be associated with a reduced risk of T2DM. These findings provide insight into the topic of bone and glucose metabolism and prompt further research in evaluating the role of bone health in the management of T2DM.