Hepatitis delta genotype 5 is associated with favourable disease outcome and better response to treatment compared to genotype 1.

BACKGROUND & AIMS: Coinfection with HDV causes rapid progression to liver cirrhosis and hepatic decompensation in patients with chronic hepatitis B. Factors that are associated with disease progression are poorly understood. In this study we aim to identify risk factors associated with disease progression and better characterise clinical differences and treatment response between HDV genotype 1 and 5. METHODS: In this retrospective study, all patients under our care between 2005 and 2016 with HBV/HDV coinfection (HBsAg+, anti-HDV antibodies positive) were analysed. Patients were excluded if follow-up was less than 6 months, if they had HCV and/or HIV coinfection or an acute HDV infection. Demographic data, stage of liver disease, development of liver complications and treatment response were recorded. RESULTS: One-hundred seven patients (mean age 36.0 years, 57% male) were followed for a median period of 4.4 years (range 0.6-28.1 years); 64% were of African origin and 17% were of European origin, with 28% of patients being cirrhotic at first visit; 43% patients had actively replicating HDV virus (anti-HDV-IgG+, anti-HDV-IgM+ or HDV RNA+) and 57% of patients were HDV exposed (anti-HDV-IgG+, HDV RNA-). Patients with actively replicating HDV more often developed liver complications than HDV-exposed patients (p = 0.002), but no differences in baseline characteristics were observed. Patients with HDV genotype 5 less often developed cirrhosis or hepatic decompensation compared to patients with HDV genotype 1. Twenty-four patients were treated with peg-IFN and post-treatment response was significantly better in patients infected with genotype 5 (10% GT1 vs. 64% GT5, p = 0.013). CONCLUSION: Patients infected with HDV genotype 5 appear to have a better prognosis with fewer episodes of hepatic decompensation and better response to peg-IFN treatment than patients infected with HDV genotype 1. LAY SUMMARY: Hepatitis delta is a virus that affects the liver. The virus is known to have different subtypes, called genotypes. With this research we discovered that hepatitis delta virus genotype 1 behaves differently than genotype 5 and causes faster development of liver disease. This is important for education of our patients and to determine how often we need to check our patients.

Mapping of fire blight resistance in Malus ×robusta 5 flowers following artificial inoculation.

BACKGROUND: Although the most common path of infection for fire blight, a severe bacterial disease on apple, is via host plant flowers, quantitative trait loci (QTLs) for fire blight resistance to date have exclusively been mapped following shoot inoculation. It is not known whether the same mechanism underlies flower and shoot resistance. RESULTS: We report the detection of a fire blight resistance QTL following independent artificial inoculation of flowers and shoots on two F1 segregating populations derived from crossing resistant Malus ×robusta 5 (Mr5) with susceptible 'Idared' and 'Royal Gala' in experimental orchards in Germany and New Zealand, respectively. QTL mapping of phenotypic datasets from artificial flower inoculation of the 'Idared' × Mr5 population with Erwinia amylovora over several years, and of the 'Royal Gala' × Mr5 population in a single year, revealed a single major QTL controlling floral fire blight resistance on linkage group 3 (LG3) of Mr5. This QTL corresponds to the QTL on LG3 reported previously for the 'Idared' × Mr5 and an 'M9' × Mr5 population following shoot inoculation in the glasshouse. Interval mapping of phenotypic data from shoot inoculations of subsets from both flower resistance populations re-confirmed that the resistance QTL is in the same position on LG3 of Mr5 as that for flower inoculation. These results provide strong evidence that fire blight resistance in Mr5 is controlled by a major QTL on LG3, independently of the mode of infection, rootstock and environment. CONCLUSIONS: This study demonstrates for the first time that resistance to fire blight caused by Erwinia amylovora is independent of the mode of inoculation at least in Malus ×robusta 5.

Can quantitative hepatitis B surface antigen levels predict the severity of liver disease in genotype E Patients?

The utility of quantitative Hepatitis B surface antigen (qHBsAg) level as a marker of chronic hepatitis B (CHB)-related liver damage is not fully delineated, but is becoming increasingly relevant. Quantitative HBsAg levels are linked with progression of liver disease in HBeAg-negative genotype B and C patients, but it is not clear whether this is consistent across all HBV genotypes. In this single-centre, cross-sectional observational study, we evaluated whether qHBsAg levels can predict the severity of liver disease in genotype E patients. Demographic characteristics, viral, biochemical markers and qHBsAg levels were assessed at time of liver biopsy [all HBV DNA>2000 IU/mL and/or abnormal alanine transaminase (ALT)]. Patients were divided into three groups according to the severity of fibrosis on biopsy: mild (F0-1), moderate (F2-4), severe (F5-6) liver disease and into two groups according to the NI grading, low (NI 0-3) and high inflammation (NI ≥4). A total of 259 HBeAg-negative CHB treatment-naive genotype E patients were studied. The median age of this cohort was 38 years, and 61% were males. Advanced (severe) fibrosis patients had higher ALT, HBV DNA, and lower HBsAg level and qHBsAg/DNA ratio. Patients with NI ≥4 had higher ALT, HBV DNA, but lower qHBsAg/DNA ratio. There was no correlation between HBsAg and HBV DNA levels. Quantitative HBsAg levels were lower in more advanced liver fibrosis. There was no correlation between qHBsAg and HBV DNA levels. This may reflect discordance between viral replication and transcriptional activity or differential HBsAg expression in HBeAg-negative genotype E patients with advanced liver disease.

Tumor Necrosis Factor-α Inhibitor Use in Psoriasis Patients With a First-degree Relative With Multiple Sclerosis.

Tumor necrosis factor (TNF)-α inhibitors are currently the gold standard for treating moderate to severe plaque psoriasis and other immune-mediated diseases. The presence of previously existing demyelinating disease is amongst the contraindications to their use. However, controversy surrounds the use of TNF-α inhibitors in patients who are more predisposed to developing multiple sclerosis (MS), specifically first-degree relatives of MS patients. In fact, the major guidelines committees' recommendations on this issue by the American Academy of Dermatology, the British Association of Dermatologists, and the European S3-Guidelines are not consistent. The data we present suggest that the number needed to treat is at least an order of magnitude smaller than the number needed to harm across all comparisons of anti-TNF-α agents and first-degree relative relationships. Based on these data, physicians could weigh the treatment options available and work closely with neurological colleagues when prescribing anti-TNF-α therapy in this patient population rather than practicing absolute prohibition of anti-TNF-α agents in patients who have a first-degree relative with MS.

Resident rounds part III: case report: a papulo- nodular eruption with systemic signs and symptoms.

This is a typical presentation of erythema nodosum leprosum in a patient with lepromatous leprosy who recently migrated from Micronesia. The clinical presentation, pathology findings, pathogenesis, and therapeutic options are reviewed here.

The spectrum of oculocutaneous disease: Part I. Infectious, inflammatory, and genetic causes of oculocutaneous disease.

Many skin diseases are associated with ocular findings, emphasizing the need for dermatologists to be fully aware of their presence, and as a result, avoid overlooking conditions with potentially major ocular complications, including blindness. We review important oculocutaneous disease associations with recommendations for the management of the ocular complications and appropriate referral to our ophthalmology colleagues. Part I of this 2-part review focuses on the infectious, inflammatory, and genetic relationships.

Redefining Disease Severity with Special Area Involvement and Reflecting on Treatment Patterns in a Real-World Psoriasis Population.

BACKGROUND: The International Psoriasis Council (IPC) recommends an approach that considers body surface area (BSA), involvement in special areas, and treatment history for classifying patients as candidates for topical or systemic treatment. This study aimed to quantify the burden of psoriasis by describing BSA distribution, special area involvement, and treatments in a real-world population. METHODS: This retrospective cohort study included patients with psoriasis from the Optum® deidentified Electronic Health Records database with a BSA value (< 3%, 3-10%, and > 10%) recorded between 1 March 2014 and 1 September 2020. Treatments and special area involvement (face, scalp, palms/soles, nails, genitals) were identified within 90 days of the BSA value and stratified by BSA category. RESULTS: Among eligible patients (N = 5120), mean age was 51.4 years and 49.3% were women. The majority of patients (78.9%) were treated with any topical. Proportions of patients with BSA < 3%, 3-10%, and > 10% were 23.4%, 41.9%, and 34.6%, respectively; proportions with 0, 1, and 2+ special areas were 21.6%, 31.6%, and 45.7%, respectively; and 44.4%, 45.7%, and 45.9% of patients with BSA < 3%, 3-10%, and > 10%, respectively, had 2+ special areas. CONCLUSION: The IPC classification can likely identify many more patients who may benefit from systemic therapy than BSA alone.

Putative resistance gene markers associated with quantitative trait loci for fire blight resistance in Malus 'Robusta 5' accessions.

BACKGROUND: Breeding of fire blight resistant scions and rootstocks is a goal of several international apple breeding programs, as options are limited for management of this destructive disease caused by the bacterial pathogen Erwinia amylovora. A broad, large-effect quantitative trait locus (QTL) for fire blight resistance has been reported on linkage group 3 of Malus 'Robusta 5'. In this study we identified markers derived from putative fire blight resistance genes associated with the QTL by integrating further genetic mapping studies with bioinformatics analysis of transcript profiling data and genome sequence databases. RESULTS: When several defined E.amylovora strains were used to inoculate three progenies from international breeding programs, all with 'Robusta 5' as a common parent, two distinct QTLs were detected on linkage group 3, where only one had previously been mapped. In the New Zealand 'Malling 9' X 'Robusta 5' population inoculated with E. amylovora ICMP11176, the proximal QTL co-located with SNP markers derived from a leucine-rich repeat, receptor-like protein (MxdRLP1) and a closely linked class 3 peroxidase gene. While the QTL detected in the German 'Idared' X 'Robusta 5' population inoculated with E. amylovora strains Ea222_JKI or ICMP11176 was approximately 6 cM distal to this, directly below a SNP marker derived from a heat shock 90 family protein gene (HSP90). In the US 'Otawa3' X 'Robusta5' population inoculated with E. amylovora strains Ea273 or E2002a, the position of the LOD score peak on linkage group 3 was dependent upon the pathogen strains used for inoculation. One of the five MxdRLP1 alleles identified in fire blight resistant and susceptible cultivars was genetically associated with resistance and used to develop a high resolution melting PCR marker. A resistance QTL detected on linkage group 7 of the US population co-located with another HSP90 gene-family member and a WRKY transcription factor previously associated with fire blight resistance. However, this QTL was not observed in the New Zealand or German populations. CONCLUSIONS: The results suggest that the upper region of 'Robusta 5' linkage group 3 contains multiple genes contributing to fire blight resistance and that their contributions to resistance can vary depending upon pathogen virulence and other factors. Mapping markers derived from putative fire blight resistance genes has proved a useful aid in defining these QTLs and developing markers for marker-assisted breeding of fire blight resistance.

Dowling-Degos disease involving the vulva and back: case report and review of the literature.

Dowling-Degos disease is a rarely encountered pigmentary disorder in which small brown-to-black macules appear in a clustered or reticulated pattern primarily at flexural sites. It usually occurs as an autosomal dominant trait but sporadic cases have also been reported. Dowling-Degos disease is sometimes associated with other cutaneous abnormalities, many of which appear to occur as a result of abnormal follicular development. The histology is distinctive with marked, heavily pigmented, slender, and often branched, elongation of the rete ridges. Dowling-Degos disease is caused by one of several loss-of-function mutations in the keratin 5 gene. Similar mutations are found in patients with Galli-Galli disease and that disorder is now considered to be a subset of Dowling-Degos disease. Medical therapy is ineffective but two patients have responded well to ablative laser therapy. We report a patient with the sporadic form of the disease who developed pigmented macules in the rarely involved sites of the lower back and vulva. Her vulvar lesions were treated with Er:YAG laser ablation.

Cutaneous porphyrias part II: treatment strategies.

The porphyrias are diverse in pathophysiology, clinical presentation, severity, and prognosis, presenting a diagnostic and therapeutic challenge. Although not easily curable, the dermatological manifestations of these diseases, photosensitivity and associated cutaneous pathology, can be effectively prevented and managed. Sun avoidance is essential, and patient education regarding the irreversibility of photocutaneous damage is a necessary corollary. Beyond preventative measures, the care of fragile, vulnerable skin, and pain management, each of the porphyrias has a limited number of unique additional therapeutic options. Many of the treatments have been published only in small case series or anecdotal reports and do not have well-understood nor proven mechanisms of action. This article presents a comprehensive review of available therapeutic options and long-term management recommendations for the cutaneous porphyrias.

Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology.

The porphyrias are a group of disorders characterized by defects in the heme biosynthesis pathway. Many present with skin findings including photosensitivity, bullae, hypertrichosis, and scarring. Systemic symptoms may include abdominal pain, neuropsychiatric changes, anemia, and liver disease. With advances in DNA analysis, researchers are discovering the underlying genetic causes of the porphyrias, enabling family members to be tested for genetic mutations. Here we present a comprehensive review of porphyria focusing on those with cutaneous manifestations. In Part I, we have included the epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Treatment and management options will be discussed in Part II.

Development and validation of an efficient in-house real-time reverse transcription polymerase chain reaction assay for the quantitative detection of serum hepatitis delta virus RNA in a diverse South London population.

Hepatitis delta virus (HDV) causes both acute and chronic hepatitis, always in the presence of hepatitis B. Analysis of global HDV isolates has shown that at least eight genotypes exist. HDV RNA quantitation and genotyping are important tools in the diagnosis and management of infected individuals. There is, as yet, no commercially available quantitative HDV RNA assay. Several laboratories have developed in-house assays, but equivalent detection and quantitation across all HDV genotypes has not been demonstrated. In this study, the development of an in-house real-time reverse transcription polymerase chain reaction (RT PCR) assay is described to quantify HDV RNA in serum or plasma. Its efficiency was validated by testing 99 samples from patients with known chronic HDV infection, along with 22 samples from individuals without HDV. The assay has a dynamic range of 6.4×10(2) to 6.4×10(8)copies/mL. Amplicons of the quantitative PCR can be directly used for sequence analysis and genotyping. HDV-1, HDV-5 and HDV-6 were identified, reflecting the areas of origin of our cohort of patients. The ability to genotype and to accurately quantify HDV RNA levels in the more recently discovered African genotypes will be important for investigating the natural history of HDV in this group, compared to those with genotype 1 disease.

The increasing prevalence of hepatitis delta virus (HDV) infection in South London.

On the basis of historical studies, hepatitis delta virus (HDV) infection is considered uncommon in the United Kingdom (UK) and mainly confined to intravenous drug users. In order to assess the current prevalence of HDV co-infection in patients with chronic hepatitis B (HBV), a retrospective analysis was performed of 962 consecutive HBV-infected adult patients referred to King's College Hospital between January 1st 2000 and March 31st 2006. The 82 subjects positive for HDV antibody (8.5%) had a similar age to those without HDV (median 36 years, interquartile range 30-47, vs. 35 years, 29-43). Excluding non-UK residents, the prevalence of HDV Antibody was 7.1%. Most HDV-infected subjects were born in regions where HDV is endemic, for example, Southern or Eastern Europe (28.1%), Africa (26.8%) or Middle-East (7.3%). Forty one (50%) were considered to have acquired HDV infection via intra-familial transmission but intravenous drug use was still a common route of transmission (24.4%). Comparing HBV/HDV co-infected to HBV mono-infected patients, a higher proportion were hepatitis C antibody positive (25.6% versus 3.8%; odds ratio 8.89, 95% confidence interval 4.4-17.9; P < 0.00001) and more had cirrhosis (26.8% vs. 12.9%; odds ratio 2.64, 95% confidence interval 1.55-4.49; P < 0.0001) but, despite this, the risk of hepatocellular carcinoma was similar (odds ratio 1.34, 95% confidence interval 0.62-2.91). Although HDV infection is reportedly declining in some endemic regions, our data demonstrate a high prevalence in South London. HDV co-infection is associated with increased morbidity and patients with HBV should be tested for HDV infection.

Avaliaçäo nutricional de pré-escolares: um subsídio para o planejamento / Nutritional evaluation in pre-school children: a support to planning

Apresentam-se os resultados de uma avaliaçäo do estado nutricional de crianças em idade pré-escolar, selecionando-se dentre os fatores condicionantes, a dieta e o poder aquisitivo familiar. Utiliza-se a classificaçäo de Waterlow (1977), recomendada pela Organizaçäo Mundial da Saúde (OMS), para identificar a prevalência, a natureza e a severidade da desnutriçäo proteico-energética, com base na antropometria. A avaliaçäo da dieta das familias com crianças de 1 a 5 anos baseia-se em 3 aspectos: fontes de energia, adequaçäo proteico-energética e diversidade. O cálculo dos requerimentos nutricionais baseou-se nas mais recentes recomendaçöes da FAO/OMS (1973, 1975). A metodologia adotada encontra-se na publicaçäo "Requerimentos Nutricionais: Metodologia Aplicada aos Dados do ENDEF" ( IBGE, 1981a) (p 66). Säo contrapostos resultados para 2 polos extremos do desenvolvimento sócio-econômico brasileiro: o Estado de Säo Paulo e a Regiäo Nordeste, subdivididos em regiöes urbana e rural, respectivamente. As conclusöes apresentadas foram extraídas do "Perfil Estatístico de Crianças e Mäes no Brasil: Aspectos Nutricionais (UNICEF/IBGE, 1981). Conclui-se que o déficit de energia é o mais importante em todos os estrados, condicionando o déficit proteico. As dietas de quase um terço (31%) da populaçäo estudada näo satisfazem nem aos requerimentos energéticos mínimos. A situaçäo alimentar é, em geral, pior no Nordeste do que em Säo Paulo, confirmando os resultados antropométricos (p81)

Propostas para o atendimento a crianças carentes de 0 a 6 anos de idade / Proposals for the care of needy children from 0 to 6 years old

Apresenta-se uma síntese da situaçäo de crianças carentes de zero a 6 anos de idade e de suas mäes, a partir da qual as propostas de intervençäo através de políticos e serviços básicos, foram elaboradas. Dois aspectos de serviços básicos foram selecionados para elaboraçäo detalhada: o atendimento em creches e serviços correlatos e atendimento baseado em intervençäo nutricional. Cada forma de atendimento é detalhada em termos de objetivos, clientela, regime de atendimento, programaçäo básica, operacionalizaçäo, recursos físicos, humanos, materiais e financeiros, participaçäo comunitária, etc. Näo obstante, o subsídio principal à elaboraçäo das propostas de intervençäo nutricional é uma série de "10 Mensagens Básicas às Mäes, que correspondem aos fundamentos da assistência infantil e indispensáveis, que as mäes devem possuir. Ademais, säo elaborados dez propostas diferentes para programas de intervençäo nutricional, incluindo várias alternativas para a realizaçäo e implementaçäo do conteúdo das "10 Mensagens Básicas", também de forma detalhada. As informaçöes de apoio incluem dados demográficos quanto à distribuiçäo de crianças de zero a 6 anos em todo o país, por regiöes e por microrregiöes, subsídios ao planejamento e à avaliaçäo de programas e também, referências bibliográficas concernentes ao assunto

Consideraçöes sobre a situaçäo das crianças carentes de 0 a 6 anos: alguns aspectos relevantes / Situation of children from 0 to 6 years old:some relevant aspects

Apresenta-se o perfil do estado nutricional de crianças carentes de zero a 6 anos de idade. Constata-se que a prevalência de desnutriçäo na populaçäo infantil é uma das mais altas da América Latina. De acordo com o sistema de Gomez, 53% de todas as crianças no Brasil, ou 12 milhöes, têm desnutriçäo de 1, 2 e 3 graus. Quanto a severidade, a prevalência dos casos mais sérios de desnutriçäo, moderada e grave, respectivamente de 2 e 3 graus, é de 16% pelo sistema de Gomez, e de 28% ou 6,2 milhöes de crianças, pelo sistema de Waterlow. Ademais, a natureza do tipo de desnutriçäo mais comumente manifestada nas crianças brasileiras é a pregressa, isto é, crescimento de altura retardado. Em bases nacionais, a desnutriçäo pregressa é oito vezes mais prevalente do que a desnutriçäo aguda (recente) (p11). Salienta-se que as diferenças regionais urbana e rural na prevalência da desnutriçäo deixam de existir, uma vez considerado determinante o fator renda per capita. Näo obstante, a cifra de 12 milhöes de desnutridos e 13 milhöes de crianças de zero a 6 anos de baixa renda, demonstram a grave situaçäo no Brasil, quanto ao problema de desnutriçäo nessa parcela da populaçäo (p12). Através de convênio firmado entre o Fundo das Naçöes Unidas para a Infância (UNICEF) e Ministério da Previdência e Assistência Social (MPAS), por intermédio de sua Secretaria de Assistência Social (SAS), säo elaboradas e apresentadas propostas de atendimento ao grupo de crianças carentes de zero a 6 anos. Pretende-se contribuir, através dos subsídios para estudos e programaçöes, à melhoria das condiçöes de saúde, nutriçäo, aprendizagem e integraçäo social de crianças nessa faixa etária, particularmente daquelas pertencentes a famílias de baixa renda

Propostas de formas alternativas de atendimento ao pré-escolar / Proposals of alternatives of preschool child care

Apresentam-se formas alternativas de atendimento às crianças carentes de zero a 6 anos de idade, aos planejadores e administradores de programas sociais, de baixo custo e ampla abrangência dirigida à populaçäo de baixa renda. Dentre as formas alternativas de atendimento, foram escolhidas e säo detalhadamente descritas, 8 propostas a saber: creche domiciliar; Programa de Atendimento ao Pré-Escolar (PROAPE); Centro Comunitário Infantil (C.C.I); subsídio familiar; criança presente na comunidade; lares substitutos ou colocaçäo familiar; creche tradicional e abrigo - lares dispersos nos bairros. As formas escolhidas priorizam a prevençäo no sentido de levar às famílias carentes a ajuda para que as crianças permaneçam neste grupo, recebendo serviços integrados e contínuos que garantam o atendimento às suas necessidades básicas. Estes atendimentos informais estäo passando, outrossim, por avaliaçöes constantes analizadas por fundaçöes e universidades, que com informaçöes já obtidas, começam a justificar e aprovar as experiências. Em cada atendimento, formal ou informal, é sugerida a sua implantaçäo em áreas rurais ou urbanas levando em consideraçäo a concentraçäo de populaçäo de zero a 6 anos. Sabe-se, que no Brasil 33% da populaçäo ainda vive na área rural e é nesta área e nas periferias das cidades de médio e grande porte que o problema da criança carenciada é mais grave e necessita de atendimento mais urgente (p20). Ademais, a proposiçäo de entrosamento das formas de atendimento, desde as mais provisórias até definitivas e permanentes, oferecem possibilidades concretas e alternativas de intervençäo e asseguram um atendimento de boa qualidade ainda que de baixo custo. Finalizando, o entrosamento da creche domiciliar com o PROAPE e o C.C.I é mais detalhado uma vez que este entrosamento garante à criança um atendimento completo e eficiente para suas necessidades básicas