Familial hypercholesterolaemia: what’s new?

Autosomal Dominant Familial Hypercholesterolaemia (FH) is the commonest inherited disorder of lipoprotein metabolism. Untreated monogenic FH caused by mutations in the LDLR, APOB or PCSK9 genes result in early onset cardiovascular death (below the age of 60 years). In the UK the prevalence of heterozygous FH is 1 in 270 and homozygous FH is 160,000 approximately.The introduction of statins nearly three decades ago has altered the natural history of FH, with a significant reduction of cardiovascular related morbidity and mortality. There is increasing evidence that early childhood interventions such as lifestyle choices, healthy eating and commencing statins by the age of 10 years would potentially prevent early onset cardiovascular disease and mortality in monogenic FH. The medium term safety of statins in children has been demonstrated. The UK paediatric FH register data has shown that children with FH are less obese than the normal population and the register aims to monitor the longer-term safety of statins in children with FH. Child-parent screening would potentially benefit the child and enables identifying a parent with FH, before the onset of a life threatening cardiovascular event. In addition, genetic cascade testing of relatives of an affected individual has been shown to be highly cost effective.We review the current literature with brief updates on genetics, the UK paediatric FH register data, published recommendations for the management of homozygous and heterozygous FH, lipid lowering therapies in children and screening for FH in childhood.     

Niacinamide and 12‐hydroxystearic acid prevented benzo(a)pyrene and squalene peroxides induced hyperpigmentation in skin equivalent

Skin surface is constantly exposed to environmental and secreted stressors such as UV, air pollution and peroxidized sebum. The current study aims to use reconstructed human skin equivalents to demonstrate topical stressor‐induced hyperpigmentation and evaluate bioactives’ potential protective effect. Given that polycyclic aromatic hydrocarbons are representative airborne particle‐bound organic compounds with known relevance to pigmentation pathways, benzo(a)pyrene was selected as surrogate environmental toxin. On the other hand, squalene monohydroperoxides are well‐characterized sebum peroxidation product under UV and pollutant exposure, thus are used as another representative skin stressor. With 3‐day continuous exposure, 30 pmol/cm² of benzo(a)pyrene and 3.4 nmol/cm² of squalene monohydroperoxides induced significant viability loss, inflammatory response, and approximately 10 shades of pigmentation increase in pigmented living skin equivalents. At the same time, pretreatment and co‐treatment with 12‐hydroxystearic acid (12‐HSA, 20 μmol/L) or niacinamide (5 mmol/L) ameliorated such stressor‐induced consequences. Niacinamide was particularly effective against benzo(a)pyrene damage, probably as a substrate for important NAD+ dependent detoxification pathways, while 12‐HSA was potent against squalene monohydroperoxides through barrier enhancing, anti‐inflammatory, and anti‐oxidative mechanisms. In summary, topical stressor‐induced hyperpigmentation was achieved in vitro, with known bioactives showing protective benefits.     

Suprascapular nerve entrapment in young kayaker: a case report

ABSTRACT

Kayaking has become one of the most popular paddle sports throughout the world. The shoulder is the most commonly injured area of the body among kayaking participants as a result of acute traumatic events and chronic overuse injuries. Therefore, kayaking participants may often seek advice for shoulder problems and there is a scarcity of studies regarding shoulder injuries in this population. In this case report, we present a young male recreational whitewater kayaker with a severe suprascapular nerve (SSN) entrapment who presented with shoulder pain and inability to perform his sport. He was initially evaluated elsewhere and was treated with nonsteroidal anti-inflammatory medications and physical therapy for presumptive diagnosis of subacromial impingement. After 5 months of failed non-operative treatment, the patient sought a second opinion with our group. SSN entrapment diagnosis was confirmed by a thorough careful physical examination, magnetic resonance imaging and electrodiagnostic study. Given the failure of non-operative treatment, the patient was treated with arthroscopic SSN decompression and successfully returned to kayaking without symptoms. While SSN entrapment has been reported in a variety of sports, especially those involving overhead movements, this is the first case report of SSN entrapment reported which impaired participation in kayaking. This case report supports the consideration of SSN entrapment in the differential diagnosis of painful shoulder among kayaking participants and highlights the importance of undressing the patient and examining the posterior shoulder for atrophy, winging or deformity.     

Therapy‐related B‐lymphoblastic leukemia associated with Philadelphia chromosome and MLL rearrangement: Single institution experience and the review of the literature

Therapy related acute lymphoblastic leukemia (t‐ALL) of B cell origin is rare and constitutes approximately 2% of all ALL. Previously compiled data on the complete cytogenetic analysis of 48 t‐B‐ALL cases suggested that MLL rearrangement at 11q23 gene locus is the most common abnormality. Philadelphia chromosome (Ph) and a normal karyotype were reported as the second and third most common karyotypes, respectively. We investigated cytogenetic karyotypes of six t‐B‐ALL cases with a pre‐B cell immunophenotype. Ph + t‐B‐ALL was noted in four of six patients previously treated with radiation and/or chemotherapy. In addition, one case demonstrated MLL rearrangement at 11q23 locus while one case demonstrated normal cytogenetic karyotype. Five of the six t‐B‐ALL patients had persistent leukemia following initiation of chemotherapy for secondary leukemia with survival ranging from 10 to 21 months. To our knowledge, only fourteen patients with Ph + t‐B‐ALL have been described in the literature. In the current study, three of four cases with Ph + t‐B‐ALL were associated with treated breast carcinoma while one patient was treated for Hodgkin lymphoma. All four patients had undergone radiation therapy. The results may indicate a plausible association between Ph+t‐B‐ALL and prior radiation exposure.