Exposure to MF59-adjuvanted influenza vaccines during pregnancy—A retrospective analysis

Pregnant women are at increased risk for complications and death associated with pandemic H1N1 influenza infection and they are prioritized for vaccination by public health authorities. Few data are available on the safety of adjuvants as components of pandemic vaccines that could be given systematically to pregnant women. Here we review nonclinical and clinical data on pregnancy outcomes associated with exposure to MF59^®, an adjuvant used in licensed H1N1 pandemic vaccines. Evaluation of the reproductive and developmental toxicity of MF59 alone and of a candidate MF59-adjuvanted H5N1 vaccine in animals demonstrated no evidence of teratogenicity or impact on fetal or early perinatal development. The clinical trial database encompassing all Novartis vaccine studies from 1991 to 2009 was searched to compare pregnancy outcomes in subjects exposed to MF59-adjuvanted or unadjuvanted influenza vaccines. Analysis of the clinical trial database found that the distribution of pregnancy outcomes (normal, abnormal, or ending in induced abortion) was similar in subjects exposed to MF59-adjuvanted and unadjuvanted influenza vaccine at any time in pregnancy and also, specifically, in early pregnancy: the respective proportions reported as a normal pregnancy outcome were 70% and 75%, respectively, overall, and 61% and 68%, respectively, in early pregnancy. Although data from the clinical database are too few to draw definitive conclusions on risks associated with exposure to MF59-adjuvanted influenza vaccines during pregnancy, available observations, so far, indicate no signals of a risk. Further data will be forthcoming from planned post-licensure studies of adjuvanted H1N1 vaccines as they are distributed in the pandemic response.     

Antibody response against heterogeneous circulating influenza virus strains elicited by MF59- and non-adjuvanted vaccines during seasons with good or partial matching between vaccine strain and clinical isolates

MF59 is already known to enhance the breadth of antibody response to mismatched influenza seasonal and avian strains. However, little is known on the effect of MF59 on immunogenicity of influenza vaccines when “apparent” good matching between circulating and vaccine strains exists. To this end, we compared the immune response elicited by MF59-adjuvanted or non-adjuvanted subunit vaccine, containing A/California/7/04(H3N2) strain, against circulating viruses isolated between 2004/2005 and 2006/2007 seasons, belonging to different clades. The advantage offered by MF59 in terms of higher immunogenicity, expressed as higher post-vaccination HI titres, is observable also against viruses showing antigenic and molecular pattern undistinguishable from vaccine strain, but it became even more evident as the antigenic and molecular distance between vaccine and circulating strains grew. These data show that seasonal influenza vaccine adjuvanted with MF59 can offer a stronger benefit as compared to non-adjuvanted vaccine in protecting against a broader range of virus strains circulating during the influenza season.     

A simulation-based comparison of techniques to correct for measurement error in matched case-control studies

The presence of measurement errors affecting the covariates in regression models is a relevant topic in many scientific areas, as, for example, in epidemiology. An example is given by an epidemiological population-based matched case-control study on the aetiology of childhood malignancies, which is currently under completion in Italy. This study was aimed at evaluating the effects of childhood exposure to extremely low electromagnetic fields on the risk of disease occurrence by taking into account the possibility of erroneous measures of the exposure. Within this framework, we focus on the application of likelihood methods to correct for measurement error. This approach, which has received less attention in literature with respect to alternatives, is compared with commonly used methods such as regression calibration and SIMEX. The comparison is performed by simulation, under a broad range of measurement error structures.     

Successful treatment of syringotropic CD8+ mycosis fungoides accompanied by hypohidrosis with vorinostat and retinoids

We describe a 34‐year‐old Japanese man with syringotropic CD8+ mycosis fungoides (MF) accompanied by hypohidrosis who was treated with vorinostat and retinoids. Interestingly, immunohistochemical staining for dermcidin revealed a decrease of sweat in the eccrine glands, and a sweat test by the iodine starch method proved hypohidrosis in the MF‐affected areas. Six months after treatment with this combination therapy, the patient's advanced MF was under control.     

MicroRNAs in Cutaneous T-Cell Lymphoma: The Future of Therapy

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Ustekinumab in severe complicated erythrodermic psoriasis: rapid clearing,safety, and sustained remission

Erythrodermic psoriasis is a severe type of psoriasis associated with comorbidities and high mortality. Patients with erythrodermic psoriasis need hospitalization and systemic treatment. Conventional drugs and biologic agents may not manage to control refractory and complicated erythrodermic psoriasis resulting from treatment failure. Ustekinumab, a human monoclonal antibody against interleukin‐12 and 23, seems to be an effective therapeutic option in erythrodermic psoriasis whenever other therapies have failed.     

Heart rate variability during extracorporeal membrane oxygenation and recovery in severe neonatal disease

BACKGROUND: Heart rate variability (HRV) reveals information on the functional state of the autonomic nervous system (ANS) in neonates. During severe illness, heart rate variability is impaired. AIM: This study was initiated to measure the changes in HRV in neonates during extracorporeal membrane oxygenation (ECMO) and recovery from severe respiratory and circulatory failure. Moreover, we compared our data with HRV data of healthy newborns and we investigated the differences in HRV parameters between ECMO-survivors and non-survivors. STUDY DESIGN: This study is of an observational character. We performed short-term recordings of heart rate variability in 14 neonates during ECMO and recovery. We computed time- and frequency-domain HRV parameters. RESULTS: ECMO significantly affects time-domain HRV parameters. Severe neonatal illness causes a significant reduction of all calculated HRV parameters; clinical recovery is accompanied by an increase of HRV. In comparison with normative data of healthy newborns, however, HRV remains impaired. The ECMO-development ratio separated the non-survivors from the survivors during ECMO therapy. CONCLUSIONS: During severe neonatal illness, HRV is impaired. It remains to be clarified whether the impairment of HRV during severe illness can predict the neurological outcome. The ability of the E/D ratio as an HRV parameter to serve as a predictive tool has to be corroborated in larger group of patients.     

膜法分级纯化姬松茸子实体多糖的研究

目的通过微滤和超滤对姬松茸子实体粗多糖分级纯化,获得最佳试验操作条件,考察各级相对分子质量范围内的多糖分布情况及所得制品的纯度。方法使用微滤和不同截留相对分子质量的超滤串联工艺。结果试验按相对分子质量将其分成>3×105、3×105~8×104,8×104~1×104以及<1×1044个级别,所得多糖质量分布比例约为5∶1∶3∶1。试验确定操作条件为室温,操作压力0.08~0.1MPa,微滤和各级超滤分别将各级多糖最高浓缩至45、35和25g/L。在低温下干燥制备的姬松茸多糖制品,质量分数高于70%,多糖总回收率高达83.7%。结论该工艺简单可行,姬松茸子实体多糖相对分子质量主要分布于>3×105和8×104~1×105。     

Two distinct variants of mycosis fungoides (MF): Folliculotropic MF and erythrodermic MF

Mycosis fungoides (MF) is the most frequent type of cutaneous T‐cell lymphoma. Folliculotropic MF (fMF) and erythrodermic MF (eMF) are two distinct variants of MF. Both variants have been considered aggressive and most cases are less responsive to standard skin‐directed therapies than classical MF. We, however, experienced many cases with fMF or eMF who showed indolent clinical courses. In this article, we reviewed 10 cases with fMF and 13 cases with eMF who came to our department between 2005 and 2017. In patients with fMF, monotherapy with topical corticosteroid was effective in two cases (20%) and ultraviolet phototherapy with oral retinoid controlled disease activity in two cases (20%). Five patients with eMF (38%) responded well to ultraviolet phototherapy. In conclusion, patients with early fMF and a subgroup of eMF patients have an indolent disease course, as was proposed among the specialists. Skin‐directed therapies are preferable rather than aggressive treatment in those cases.