Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Guy's cancer cohort - real world evidence for cancer pathways.

BACKGROUND: The burden of disease due to cancer remains substantial. Since the value of real-world evidence has also been recognised by regulatory agencies, we established a Research Ethics Committee (REC) approved research database for cancer patients (Reference: 18/NW/0297). CONSTRUCTION AND CONTENT: Guy's Cancer Cohort introduces the concept of opt-out consent processes for research in a subset of oncology patients diagnosed and treated at a large NHS Trust in the UK. From April 2016 until March 2017, 1388 eligible patients visited Guy's and St Thomas' NHS Foundation Trust (GSTT) for breast cancer management. For urological cancers this number was 1757 and for lung cancer 677. The Cohort consists of a large repository of routinely collected clinical data recorded both retrospectively and prospectively. The database contains detailed clinical information collected at various timepoints across the treatment pathway inclusive of diagnostic data, and data on disease progression, recurrence and survival. CONCLUSIONS: Guy's Cancer Cohort provides a valuable infrastructure to answer a wide variety of research questions of a clinical, mechanistic, and supportive care nature. Clinical research using this database will result in improved patient safety and experience. Guy's Cancer Cohort promotes collaborative research and will accept applications for the release of anonymised datasets for research purposes.

Happle-Tinschert, Curry-Jones and segmental basal cell naevus syndromes, overlapping disorders caused by somatic mutations in hedgehog signalling genes: the mosaic hedgehog spectrum.

Happle-Tinschert syndrome (HTS) and Curry-Jones syndrome (CJS; OMIM 601707) are rare, sporadic, multisystem disorders characterized by hypo- and hyperpigmented skin patches following Blaschko's lines, plus acral skeletal and other abnormalities. The blaschkoid pattern implies mosaicism, and indeed CJS was found in 2016 to be caused by a recurrent postzygotic mutation in a gene of the hedgehog signalling pathway, namely SMO, c.1234C>T, p.Leu412Phe. More recently the original case of HTS was found to carry the same somatic mutation. Despite this genetic and phenotypic overlap, two significant differences remained between the two syndromes. The histological hallmark of HTS, basaloid follicular hamartomas, is not a feature of CJS. Meanwhile, the severe gastrointestinal manifestations regularly reported in CJS had not been described in HTS. We report a patient whose phenotype was entirely consistent with HTS apart from intractable constipation, and a second patient with classic features of CJS plus early-onset medulloblastoma, a feature of basal cell naevus syndrome (BCNS). Both had the same recurrent SMO mutation. This prompted a literature review that revealed a case with the same somatic mutation, with basaloid follicular hamartomas and other features of both CJS and BCNS. Segmental BCNS can also be caused by a somatic mutation in PTCH1. We thus demonstrate for the first time phenotypic and genetic overlap between HTS, CJS and segmental BCNS. All of these conditions are caused by somatic mutations in genes of the hedgehog signalling pathway and we therefore propose the unifying term 'mosaic hedgehog spectrum'. What's already known about this topic? Happle-Tinschert syndrome (HTS) and Curry-Jones syndrome (CJS) are rare mosaic multisystem disorders with linear skin lesions. CJS is characterized by severe constipation, which has not previously been reported in HTS. HTS is characterized by basaloid follicular hamartomas, which are not a recognized feature of CJS. The recurrent mosaic SMO mutation found in CJS was recently reported in a patient with HTS. What does this study add? We describe a patient with HTS and intractable constipation, and a case of CJS with medulloblastoma. Both patients had the same recurrent somatic SMO mutation also found in a case reported as segmental basal cell naevus syndrome. SMO functions in the hedgehog pathway, explaining phenotypic overlap between HTS, CJS and mosaic basal cell naevus syndrome. We propose the term 'mosaic hedgehog spectrum' for these overlapping conditions.

Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility.

BACKGROUND: Several new genes and clinical subtypes have been identified since the publication in 2014 of the report of the last International Consensus Meeting on Epidermolysis Bullosa (EB). OBJECTIVES: We sought to reclassify disorders with skin fragility, with a focus on EB, based on new clinical and molecular data. METHODS: This was a consensus expert review. RESULTS: In this latest consensus report, we introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Other disorders with skin fragility, where blisters are a minor part of the clinical picture or are not seen because skin cleavage is very superficial, are classified as separate categories. These include peeling skin disorders, erosive disorders, hyperkeratotic disorders, and connective tissue disorders with skin fragility. Because of the common manifestation of skin fragility, these 'EB-related' disorders should be considered under the EB umbrella in terms of medical and socioeconomic provision of care. CONCLUSIONS: The proposed classification scheme should be of value both to clinicians and researchers, emphasizing both clinical and genetic features of EB. What is already known about this topic? Epidermolysis bullosa (EB) is a group of genetic disorders with skin blistering. The last updated recommendations on diagnosis and classification were published in 2014. What does this study add? We introduce the concept of genetic disorders with skin fragility, of which classical EB represents the prototype. Clinical and genetic aspects, genotype-phenotype correlations, disease-modifying factors and natural history of EB are reviewed. Other disorders with skin fragility, e.g. peeling skin disorders, erosive disorders, hyperkeratotic disorders, and connective tissue disorders with skin fragility are classified as separate categories; these 'EB-related' disorders should be considered under the EB umbrella in terms of medical and socioeconomic provision of care. Linked Comment: Pope. Br J Dermatol 2020; 183:603.

Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.

BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.

Classification of aplasia cutis congenita: a 25-year review of cases presenting to a tertiary paediatric dermatology department.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare, congenital disorder characterized by localized or widespread absence of skin at birth with heterogeneous clinical presentation. The classification proposed by Frieden in 1986 is widely used. AIM: To establish whether, 34 years on, the Frieden classification still meets the needs of dermatologists. METHODS: We conducted a retrospective chart review of all patients with a diagnosis of ACC presenting over a 25-year period to a tertiary paediatric dermatology department. We compiled demographic data, clinical characteristics (e.g. number, location and morphology of the lesions), imaging and genetic results where available, and other associated abnormalities, and grouped them according to the Frieden classification. For Type 6 ACC (Bart syndrome) we reviewed neonatal photographs of all babies born with epidermolysis bullosa (EB) over 5 years. RESULTS: Excluding Type 6, there were 56 children with ACC. The scalp was involved in 82.1%, and Type 1 was the commonest type. Over 5 years, 13 of 108 neonates (12%) with EB were born with the appearance of Type 6 ACC. Two children did not fit Frieden's original classification and one had a previously undescribed association of ACC with cleft lip/palate-ectodermal dysplasia 1 syndrome. CONCLUSION: We conclude that the Frieden classification remains valid with some modifications. Type 3 ACC probably represents a mosaic RASopathy syndrome, while Type 7 could cover nongenetic ACC attributable to trauma. Type 8 should be subdivided into two subgroups: teratogenic and infective. Type 9 covers at least four subgroups. The classification will continue to evolve as new genes and pathomechanisms emerge.

Midface toddler excoriation syndrome (MiTES) can be caused by autosomal recessive biallelic mutations in a gene for congenital insensitivity to pain, PRDM12.

BACKGROUND: Midface toddler excoriation syndrome (MiTES) is a condition recently reported in three unrelated children. Habitual scratching from the first year of life inflicted deep, chronic, scarring wounds around the nose and eyes. One child had a mild neurological deficit but there was no other evidence of insensitivity to pain. Bilateral distribution and localization to the midface distinguish MiTES from other causes of self-inflicted skin damage such as trigeminal trophic syndrome. An earlier study of five siblings from a consanguineous Irish family, with lesions corresponding to MiTES plus other sensory deficits, showed homozygous mutations in a gene for hereditary sensory and autonomic neuropathy type VIII (HSAN8), PRDM12. OBJECTIVES: To study further cases of MiTES, including analysis of PRDM12. METHODS: We describe five further children, from four families, with facial lesions typical of MiTES, in whom mutation analysis of PRDM12 was carried out. RESULTS: Homozygous or compound heterozygous pathogenic expansions of the PRDM12 polyalanine tract were found in four of five affected individuals, in three families. CONCLUSIONS: Our finding of autosomal recessive mutations in PRDM12 in four of five patients with MiTES extends the phenotypic spectrum of PRDM12 mutations, which usually cause HSAN8, characterized by mutilating self-inflicted wounds of the extremities, lips and tongue. By contrast, MiTES shows severe midfacial lesions with little if any evidence of generalized pain insensitivity. The condition is probably genetically heterogeneous, and other congenital insensitivity to pain and HSAN genes such as SCN11A may be implicated. This new understanding of the nature of MiTES, which can masquerade as factitious disease, will facilitate appropriate management.

A 10-year longitudinal follow-up study of a U.K. paediatric transplant population to assess for skin cancer.

BACKGROUND: Our earlier study, published in 2004,found no skin cancer in a cohort of paediatric organ transplant recipients (POTRs) 5-16 years post-transplantation. We re-evaluated the same cohort 10 years later. OBJECTIVES: To determine the prevalence of premalignant and malignant skin lesions and identify known risk factors associated with melanocytic naevi in a U.K. paediatric transplant population. METHODS: Ninety-eight POTRs from the original 2004 study were invited to participate in this longitudinal follow-up study. History of sun exposure, demographics and transplantation details were collected using face-to-face interviews, questionnaires and case note reviews. Skin examination was performed for regional count of malignant lesions, benign and atypical naevi. RESULTS: Of the 98 patients involved in the initial study, 45 POTRs (eight kidney, 37 liver), with a median follow-up of 19 years (range 15-26 years), agreed to participate. Neither skin cancer nor premalignant lesions were detected in these patients. When compared with the 2004 cohort, 41 patients in our current cohort had increased numbers of benign naevi (P < 0·001) with 11 patients having ≥ 50 benign naevi. Seventy-one per cent of benign naevi in our 2014 cohort occurred on sun-exposed sites (13% head/neck, 35% arms and 23% legs). Patients who regularly used sunscreen had more benign naevi on their arms (P = 0·008). CONCLUSIONS: Although skin cancer was not observed in our cohort, we identified a significant increase in the number of benign naevi, particularly in those reporting frequent sunburn and sunscreen use.

Functional role of airflow-sensing hairs on the bat wing.

The wing membrane of the big brown bat (Eptesicus fuscus) is covered by a sparse grid of microscopic hairs. We showed previously that various tactile receptors (e.g., lanceolate endings and Merkel cell neurite complexes) are associated with wing-hair follicles. Furthermore, we found that depilation of these hairs decreased the maneuverability of bats in flight. In the present study, we investigated whether somatosensory signals arising from the hairs carry information about airflow parameters. Neural responses to calibrated air puffs on the wing were recorded from primary somatosensory cortex of E. fuscus Single units showed sparse, phasic, and consistently timed spikes that were insensitive to air-puff duration and magnitude. The neurons discriminated airflow from different directions, and a majority responded with highest firing rates to reverse airflow from the trailing toward the leading edge of the dorsal wing. Reverse airflow, caused by vortices, occurs commonly in slowly flying bats. Hence, the present findings suggest that cortical neurons are specialized to monitor reverse airflow, indicating laminar airflow disruption (vorticity) that potentially destabilizes flight and leads to stall. NEW & NOTEWORTHY: Bat wings are adaptive airfoils that enable demanding flight maneuvers. The bat wing is sparsely covered with sensory hairs, and wing-hair removal results in reduced flight maneuverability. Here, we report for the first time single-neuron responses recorded from primary somatosensory cortex to airflow stimulation that varied in amplitude, duration, and direction. The neurons show high sensitivity to the directionality of airflow and might act as stall detectors.

The relationship of bone properties using high resolution peripheral quantitative computed tomography to radiographic components of hip osteoarthritis.

OBJECTIVE: Positive associations between radiographic osteoarthritis (OA) and areal bone mineral density (BMD) have been demonstrated and appear strongest when bony features of OA are considered. To date, these associations have not been assessed using HRpQCT. DESIGN: A total of 318 participants (170 men and 148 women), aged 72.1-81.4 years from a non-selected cohort, underwent HRpQCT of the distal radius and tibia along with hip radiography. Differences in bone microarchitecture were assessed between those with and without osteophytes, sclerosis or joint space narrowing (JSN) in either hip. RESULTS: Men with osteophytes alone had significantly higher radial trabecular volumetric BMD (Tb.vBMD) and radial and tibial trabecular thickness (Tb.Th). Men with both sclerosis and osteophytes had significantly higher cortical volumetric BMD (Ct.vBMD) and cortical thickness (Ct.Th) at the distal tibia than those with osteophytes alone (P < 0.05). These relationships were maintained after adjustment for age and Body Mass Index (BMI), and were not replicated in women. Bone microarchitecture did not differ significantly in those with JSN from those without it in men or women. CONCLUSIONS: Our findings suggest higher Tb.vBMD and Tb.Th in men with osteophytosis but higher tibial Ct.vBMD and Ct.Th in men with hip joint sclerosis. These results do however require replication in other cohorts.

A novel accelerometer-based method to describe day-to-day exposure to potentially osteogenic vertical impacts in older adults: findings from a multi-cohort study.

This observational study assessed vertical impacts experienced in older adults as part of their day-to-day physical activity using accelerometry and questionnaire data. Population-based older adults experienced very limited high-impact activity. The accelerometry method utilised appeared to be valid based on comparisons between different cohorts and with self-reported activity. INTRODUCTION: We aimed to validate a novel method for evaluating day-to-day higher impact weight-bearing physical activity (PA) in older adults, thought to be important in protecting against osteoporosis, by comparing results between four cohorts varying in age and activity levels, and with self-reported PA levels. METHODS: Participants were from three population-based cohorts, MRC National Survey of Health and Development (NSHD), Hertfordshire Cohort Study (HCS) and Cohort for Skeletal Health in Bristol and Avon (COSHIBA), and the Master Athlete Cohort (MAC). Y-axis peaks (reflecting the vertical when an individual is upright) from a triaxial accelerometer (sampling frequency 50 Hz, range 0-16 g) worn at the waist for 7 days were classified as low (0.5-1.0 g), medium (1.0-1.5 g) or higher (≥1.5 g) impacts. RESULTS: There were a median of 90, 41 and 39 higher impacts/week in NSHD (age 69.5), COSHIBA (age 76.8) and HCS (age 78.5) participants, respectively (total n = 1512). In contrast, MAC participants (age 68.5) had a median of 14,322 higher impacts/week. In the three population cohorts combined, based on comparison of beta coefficients, moderate-high-impact activities as assessed by PA questionnaire were suggestive of stronger association with higher impacts from accelerometers (0.25 [0.17, 0.34]), compared with medium (0.18 [0.09, 0.27]) and low impacts (0.13 [0.07,0.19]) (beta coefficient, with 95 % CI). Likewise in MAC, reported moderate-high-impact activities showed a stronger association with higher impacts (0.26 [0.14, 0.37]), compared with medium (0.14 [0.05, 0.22]) and low impacts (0.03 [-0.02, 0.08]). CONCLUSIONS: Our new accelerometer method appears to provide valid measures of higher vertical impacts in older adults. Results obtained from the three population-based cohorts indicate that older adults generally experience very limited higher impact weight-bearing PA.

Development of a clinical diagnostic matrix for characterizing inherited epidermolysis bullosa.

BACKGROUND: Accurately diagnosing the subtype of epidermolysis bullosa (EB) is critical for management and genetic counselling. Modern laboratory techniques are largely inaccessible in developing countries, where the diagnosis remains clinical and often inaccurate. OBJECTIVES: To develop a simple clinical diagnostic tool to aid in the diagnosis and subtyping of EB. METHODS: We developed a matrix indicating presence or absence of a set of distinctive clinical features (as rows) for the nine most prevalent EB subtypes (as columns). To test an individual patient, presence or absence of these features was compared with the findings expected in each of the nine subtypes to see which corresponded best. If two or more diagnoses scored equally, the diagnosis with the greatest number of specific features was selected. The matrix was tested using findings from 74 genetically characterized patients with EB aged > 6 months by an investigator blinded to molecular diagnosis. For concordance, matrix diagnoses were compared with molecular diagnoses. RESULTS: Overall, concordance between the matrix and molecular diagnoses for the four major types of EB was 91·9%, with a kappa coefficient of 0·88 [95% confidence interval (CI) 0·81-0·95; P < 0·001]. The matrix achieved a 75·7% agreement in classifying EB into its nine subtypes, with a kappa coefficient of 0·73 (95% CI 0·69-0·77; P < 0·001). CONCLUSIONS: The matrix appears to be simple, valid and useful in predicting the type and subtype of EB. An electronic version will facilitate further testing.

Mosaic NRAS Q61R mutation in a child with giant congenital melanocytic naevus, epidermal naevus syndrome and hypophosphataemic rickets.

The association of hypophosphataemic rickets with verrucous epidermal naevus (EN) and elevated fibroblast growth factor 23 levels is known as cutaneous-skeletal hypophosphataemia syndrome (CSHS), and can be caused by somatic activating mutations in RAS genes. We report a unique patient with CSHS associated with giant congenital melanocytic naevus (CMN), neurocutaneous melanosis and EN syndrome, manifesting as facial linear sebaceous naevus, developmental delay and ocular dermoids. An activating mutation Q61R in the NRAS gene was found in affected skin and ocular tissue but not blood, implying that the disparate manifestations are due to a multilineage activating mutation (mosaic RASopathy). We speculate on the apparently rare association of CSHS with CMN compared with EN. We also report the favourable outcome of this patient at the age of 8 years after extensive neonatal curettage of the giant CMN and use of vitamin D and phosphate supplementation.

Mid-face toddler excoriation syndrome (MiTES): a new paediatric diagnosis.

Chronic ulcerating lesions on the face are rarely seen in toddlers. Blistering disease, vasculitis, infections and self-mutilation due to neurometabolic disease can usually be excluded on clinical and histological grounds. In the absence of identifiable disease, such lesions are sometimes attributed to child abuse or fabricated illness. We describe three toddlers with chronic mid-face erosions, two from India and one from the UK. One had moderate developmental delay and one had had seizures. The lesions appeared to be self-inflicted, no underlying disease was identified and there was no suspicion of child abuse. Recognition of the same disease pattern in different continents implies a distinct pathological entity. The pattern closely resembles that seen in some patients with mutations in the pain-insensitivity genes PRDM12 and SCN11A. We suggest the term 'mid-face toddler excoriation syndrome' (MiTES) to acknowledge the existence of this condition, encourage further reports and help clarify the pathogenesis.

A stratified analysis of the perioperative outcome of 17623 patients undergoing major head and neck cancer surgery in England over 10 years: Towards an Informatics-based Outcomes Surveillance Framework.

OBJECTIVES: To perform a national analysis of the perioperative outcome of major head and neck cancer surgery to develop a stratification strategy and outcomes assessment framework using hospital administrative data. DESIGN: A Hospital Episode Statistics N = near-all analysis. SETTINGS: The English National Health Service. MAIN OUTCOME MEASURES: Local audit data were used to assess and triangulate the quality of the administrative dataset. Within the national dataset, cancer sites, morbidities, social deprivation, treatment, complications, and in-hospital mortality were recorded. RESULTS: Within local audit datasets, the accuracy of assigning newly-derived Cancer Site Strata and Resection Strata were 92.3% and 94.2%, respectively. Accuracy of morbidities assignment was 97%. Within the national dataset, we identified 17 623 major head and neck cancer resections between 2002 and 2012. There were 12 413 males and mean age at surgery was 63 ± 12 years. The commonest cancer site strata were oral cavity (42%) and larynx-hypopharynx (32%). The commonest resection site was the larynx (n = 4217), and 13 211 and 11 841 patients had neck dissection and flap-based reconstruction, respectively. There were prognostically significant baseline differences between patients with oromandibular and pharyngolaryngeal malignancy. Patients with pharyngolaryngeal malignancies had a greater burden of morbidities, lower socio-economic status, fewer primary resections, and a sixfold increased risk of undergoing their major resection during an emergency hospital admission. Mean length of stay was 25 days and each complication linearly increased it by 9.6 days. There were 609 (3.5%) in-hospital deaths and a basket of seven medical and three surgical complications significantly increased the risk of in-hospital death. At least one potentially lethal complication occurred in 26% of patients. The risk of in-hospital death in a patient with no potentially lethal complication was 1.1% and this increased to 6% with one potentially lethal complication, and to 15.1% if two potentially lethal complications occurred in one patient. Complex oral-pharyngeal resections and pharyngolaryngectomies had the highest risks of complications and mortality. CONCLUSION: Mortality following head and neck cancer surgery shows variation across different resection strata. We propose an Informatics-based Framework for Outcomes Surveillance (IFOS) in Head and Neck Surgery for perpetual quality assurance, using the local hospital coding data or its collated destination, the national administrative dataset.

Lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with bone microstructure abnormalities in women.

In older women, the presence of lower leg arterial calcification assessed by high-resolution peripheral quantitative computed tomography is associated with relevant bone microstructure abnormalities at the distal tibia and distal radius. INTRODUCTION: Here, we report the relationships of bone geometry, volumetric bone mineral density (BMD) and bone microarchitecture with lower leg arterial calcification (LLAC) as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: We utilized the Hertfordshire Cohort Study (HCS), where we were able to study associations between measures obtained from HR-pQCT of the distal radius and distal tibia in 341 participants with or without LLAC. Statistical analyses were performed separately for women and men. We used linear regression models to investigate the cross-sectional relationships between LLAC and bone parameters. RESULTS: The mean (SD) age of participants was 76.4 (2.6) and 76.1 (2.5) years in women and men, respectively. One hundred and eleven of 341 participants (32.6 %) had LLAC that were visible and quantifiable by HR-pQCT. The prevalence of LLAC was higher in men than in women (46.4 % (n = 83) vs. 17.3 % (n = 28), p < 0.001). After adjustment for confounding factors, we found that women with LLAC had substantially lower Ct.area (ß = -0.33, p = 0.016), lower Tb.N (ß = -0.54, p = 0.013) and higher Tb.Sp (ß = 0.54, p = 0.012) at the distal tibia and lower Tb.Th (ß = -0.49, p = 0.027) at the distal radius compared with participants without LLAC. Distal radial or tibial bone parameter analyses in men according to their LLAC status revealed no significant differences with the exception of Tb.N (ß = 0.27, p = 0.035) at the distal tibia. CONCLUSION: In the HCS, the presence of LLAC assessed by HR-pQCT was associated with relevant bone microstructure abnormalities in women. These findings need to be replicated and further research should study possible pathophysiological links between vascular calcification and osteoporosis.

Ischemic heart disease is associated with lower cortical volumetric bone mineral density of distal radius.

UNLABELLED: In this study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to investigate geometric, volumetric and microstructural parameters at the distal radius and at the distal tibia in participants with ischaemic heart disease. We found that, compared with participants without ischaemic heart disease, they had substantially lower cortical volumetric bone mineral density (BMD) at the distal radius. INTRODUCTION: HR-pQCT captures novel aspects of bone geometry and volumetric bone mineral density (vBMD) and offers the ability to measure bone microarchitecture, but data relating measures obtained from this technique in patients with ischemic heart disease (IHD) are lacking. METHODS: Here, we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between measures obtained from HR-pQCT of distal radius and distal tibia in 350 participants (184 men and 166 women) aged 71.5-80.5 years with or without IHD (e.g. heart attack, angina or heart failure; n = 75 and n = 275, respectively). RESULTS: Analyses for all participants (men and women together) revealed that cortical vBMD (Ct.vBMD) was lower (p < 0.001) and cortical thickness (Ct.th) was not different (p = 0.519), whereas cortical porosity (Ct.Po) was higher (p = 0.016) in participants with IHD at the distal radius. Moreover, trabecular microarchitectural parameters were not significantly different in patients with IHD (p > 0.05 for all). Adjustment for a priori confounders (age, gender, body mass index, smoking status, alcohol consumption, high blood pressure and diabetes mellitus) did not materially affect the relationship described for Ct.vBMD (p = 0.002), but differences in Ct.Po were attenuated. Analyses in men alone revealed that only Ct.vBMD was lower at the distal radius in participants with IHD with and without adjustment for a priori confounders (p = 0.0002 and p = 0.004, respectively), whereas no statistical differences were found in women, although patterns of differences were similar in both sexes. Moreover, no association was found between IHD and bone parameters at the distal tibia either in men or women. CONCLUSIONS: We have demonstrated that IHD is associated with lower Ct.vBMD of the distal radius.

Effective secondary fracture prevention: implementation of a global benchmarking of clinical quality using the IOF Capture the Fracture® Best Practice Framework tool.

UNLABELLED: Fracture Liaison Services are the best model to prevent secondary fractures. The International Osteoporosis Foundation developed a Best Practice Framework to provide a quality benchmark. After a year of implementation, we confirmed that a single framework with set criteria is able to benchmark services across healthcare systems worldwide. INTRODUCTION: Despite evidence for the clinical effectiveness of secondary fracture prevention, translation in the real-world setting remains disappointing. Where implemented, a wide variety of service models are used to deliver effective secondary fracture prevention. To support use of effective models of care across the globe, the International Osteoporosis Foundation's Capture the Fracture® programme developed a Best Practice Framework (BPF) tool of criteria and standards to provide a quality benchmark. We now report findings after the first 12 months of implementation. METHODS: A questionnaire for the BPF was created and made available to institutions on the Capture the Fracture website. Responses from institutions were used to assign gold, silver, bronze or black (insufficient) level of achievements mapped across five domains. Through an interactive process with the institution, a final score was determined and published on the Capture the Fracture website Fracture Liaison Service (FLS) map. RESULTS: Sixty hospitals across six continents submitted their questionnaires. The hospitals served populations from 20,000 to 15 million and were a mix of private and publicly funded. Each FLS managed 146 to 6200 fragility fracture patients per year with a total of 55,160 patients across all sites. Overall, 27 hospitals scored gold, 23 silver and 10 bronze. The pathway for the hip fracture patients had the highest proportion of gold grading while vertebral fracture the lowest. CONCLUSION: In the first 12 months, we have successfully tested the BPF tool in a range of health settings across the globe. Initial findings confirm a significant heterogeneity in service provision and highlight the importance of a global approach to ensure high quality secondary fracture prevention services.

Familial progressive hyper- and hypopigmentation and malignancy in two families with new mutations in KITLG.

BACKGROUND: Familial progressive hyper- and hypopigmentation (FPHH) is an autosomal dominant skin condition presenting in childhood with generalized macular dyspigmentation, usually reported in patients of East Asian origin. It overlaps phenotypically with other dyschromatoses, but can now be distinguished by mutations in the KIT ligand gene (KITLG). AIM: We report two unrelated white families with similar phenotypic presentations of FPHH developing in early childhood in several generations. METHODS: Sanger sequencing of the exons and flanking introns of KITLG was performed. RESULTS: This identified a new heterozygous missense mutation in each family (p.Thr34Asn and p.Val37Gly, respectively). Of the six affected individuals examined by us, two had cancer: a 62-year-old man in family 1 had developed two primary melanomas and a pharyngeal carcinoma, and a 42-year-old woman in family 2 had developed thyroid carcinoma. All had unusually sparse lateral eyebrows, a finding not previously reported in this condition. CONCLUSIONS: We summarize the genetic spectrum of the dyschromatoses and discuss a possible increased risk of malignancy in FPHH.