Background: Important progress has been made in our understanding of the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert–Eaton myasthenic syndrome (LEMS) and ...neuromyotonia (Isaacs’ syndrome).
Methods: To prepare consensus guidelines for the treatment of the autoimmune NMT disorders, references retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts.
Conclusions: Anticholinesterase drugs should be given first in the management of MG, but with some caution in patients with MuSK antibodies (good practice point). Plasma exchange is recommended in severe cases to induce remission and in preparation for surgery (recommendation level B). IvIg and plasma exchange are effective for the treatment of MG exacerbations (recommendation level A). For patients with non‐thymomatous MG, thymectomy is recommended as an option to increase the probability of remission or improvement (recommendation level B). Once thymoma is diagnosed, thymectomy is indicated irrespective of MG severity (recommendation level A). Oral corticosteroids are first choice drugs when immunosuppressive drugs are necessary (good practice point). When long‐term immunosuppression is necessary, azathioprine is recommended to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (recommendation level A). 3,4‐Diaminopyridine is recommended as symptomatic treatment and IvIG has a positive short‐term effect in LEMS (good practice point). Neuromyotonia patients should be treated with an antiepileptic drug that reduces peripheral nerve hyperexcitability (good practice point). For paraneoplastic LEMS and neuromyotonia optimal treatment of the underlying tumour is essential (good practice point). Immunosuppressive treatment of LEMS and neuromyotonia should be similar to MG (good practice point).
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Paraneoplastic myasthenia gravis (MG) is accompanied by a neoplasm, usually thymoma. In patients with thymoma and a specific genetic make‐up, the paraneoplastic immune response develops further in ...thymic remnant or peripheral lymphatic tissue. Paraneoplastic MG and late‐onset MG (age ≥ 50 years) share a similar immunological profile with high titin and ryanodine receptor (RyR) antibody prevalence. This profile is the most important predictor of clinical outcome in paraneoplastic MG. The presence of a thymoma per se does not cause more severe MG. MG severity is linked to the patient’s immunological profile. Paraneoplastic MG causes a distinctive non‐limb symptom profile at MG onset, characterized by bulbar, ocular, neck, and respiratory symptoms. When the diagnosis of paraneoplastic MG is established, the neoplasm should be removed surgically. Pre‐thymectomy plasmapheresis or iv‐IgG should be considered in these patients to minimize post‐thymectomy MG exacerbation risk. Paraneoplastic MG usually continues after thymectomy. The pharmacological treatment of paraneoplastic MG does not differ from non‐paraneoplastic MG, except for tacrolimus that should be considered in difficult cases. Tacrolimus is an immunosuppressant acting specifically in RyR antibody positive patients through enhancing RyR‐related sarcoplasmic calcium release that in theory might be blocked by RyR antibodies, causing symptomatic relief in paraneoplastic MG.
Resection of meningiomas involving the cavernous sinus often is incomplete and associated with considerable morbidity. As a result, an increasing number of patients with such tumors have been treated ...with gamma knife surgery (GKS). However, few studies have investigated the long-term outcome for this group of patients.
100 patients (23 male/77 female) with meningiomas involving the cavernous sinus received GKS at the Department of Neurosurgery at Haukeland University Hospital, Bergen, Norway, between November 1988 and July 2006. They were followed for a mean of 82.0 (range, 0-243) months. Only 2 patients were lost to long-term follow-up. Sixty patients underwent craniotomy before radiosurgery, whereas radiosurgery was the primary treatment for 40 patients.
Tumor growth control was achieved in 84.0% of patients. Twelve patients required re-treatment: craniotomy (7), radiosurgery (1), or both (4). Three out of 5 patients with repeated radiosurgery demonstrated secondary tumor growth control. Excluding atypical meningiomas, the growth control rate was 90.4%. The 1-, 5-, and 10-year actuarial tumor growth control rates are 98.9%, 94.2%, and 91.6%, respectively. Treatment failure was preceded by clinical symptoms in 14 of 15 patients. Most tumor growths appeared within 2.5 years. Only one third grew later (range, 6-20 yr). The complication rate was 6.0%: optic neuropathy (2), pituitary dysfunction (3), worsening of diplopia (1), and radiation edema (1). Mortality was 0. At last follow-up, 88.0% were able to live independent lives.
GKS gives long-term growth control and has a low complication rate. Most tumor growths manifest within 3 years following treatment. However, some appear late, emphasizing the need for long-term follow-up.
Objectives
Myasthenia gravis (MG) represents a spectrum of clinical subtypes with differences in disease mechanisms and treatment response. MG with muscle‐specific tyrosine kinase (MuSK) antibodies ...accounts for 1%‐10% of all MG patients. We conducted a meta‐analysis to evaluate the association between HLA genes and MuSK‐MG susceptibility.
Subjects and methods
Studies were searched in Pubmed, EMBASE database and other sources between 2001 and 2018. Genotype, allele and haplotype frequencies of HLA loci in MuSK‐MG patients and healthy controls were extracted from each included study.
Results
The meta‐analysis showed that HLA DQB1*05, DRB1*14 and DRB1*16 were strongly associated with an increased risk of MuSK‐MG (P < .0001), whereas HLA DQB*03 was less frequent in MuSK patients compared with healthy controls (P < .05). Haplotype analysis showed that these DQB1 and DRB1 alleles were closely linked, forming both risk (DQ5‐DR14, DQ5‐DR16, P < .0001) and protective (DQ3‐DR4, DQ3‐DR11, P < .05) haplotypes.
Conclusion
The distinct genetic patterns of MuSK‐MG indicate that variation in HLA class II genes plays an important role in the pathogenesis of MuSK‐MG patients.
Objective: This paper describes the ad hoc methodological concepts and procedures developed to improve the comparability of Nutrient databases (NDBs) across the 10 European countries participating in ...the European Prospective Investigation into Cancer and Nutrition (EPIC). This was required because there is currently no European reference NDB available. Design: A large network involving national compilers, nutritionists and experts on food chemistry and computer science was set up for the 'EPIC Nutrient DataBase' (ENDB) project. A total of 550-1500 foods derived from about 37 000 standardized EPIC 24-h dietary recalls (24-HDRS) were matched as closely as possible to foods available in the 10 national NDBs. The resulting national data sets (NDS) were then successively documented, standardized and evaluated according to common guidelines and using a DataBase Management System specifically designed for this project. The nutrient values of foods unavailable or not readily available in NDSs were approximated by recipe calculation, weighted averaging or adjustment for weight changes and vitamin/mineral losses, using common algorithms. Results: The final ENDB contains about 550-1500 foods depending on the country and 26 common components. Each component value was documented and standardized for unit, mode of expression, definition and chemical method of analysis, as far as possible. Furthermore, the overall completeness of NDSs was improved (>or=99%), particularly for β-carotene and vitamin E. Conclusion: The ENDB constitutes a first real attempt to improve the comparability of NDBs across European countries. This methodological work will provide a useful tool for nutritional research as well as end-user recommendations to improve NDBs in the future.
Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we ...investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive ER+/PR+ and 1,018 estrogen and progesterone receptor negative ER−/PR−). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio HR = 0.94 95% confidence interval CI: 0.88, 1.00 ptrend = 0.048, and HR = 0.93 95% CI: 0.87, 0.99 ptrend = 0.037, respectively). The association was more pronounced in ER−/PR− tumors (HR = 0.80 95% CI: 0.65, 0.99 ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor‐negative tumors. The results support the potential scope for BC prevention through dietary modification.
What's new?
Many factors can affect susceptibility to breast cancer, including menopausal status and diet. This study investigated the association between breast cancer and an adapted version of the “Mediterranean diet,” excluding alcohol. They found that the diet reduced the risk of breast cancer by 6% overall, and by 7% in postmenopausal women. For tumors lacking the estrogen or progesterone receptors, however, the diet reduced risk by 20% in postmenopausal women. This study also confirmed a previously observed lack of association between Mediterranean diet and breast cancer in premenopausal women.
Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and ...vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor ER, progesterone receptor PR and human epidermal growth factor receptor 2 HER2), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4‐Q1 = 1.26; 95% CI 1.00–1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4‐Q1 = 1.29; 95% CI 1.02–1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
What's new?
Does B‐vitamin intake play a role in breast cancer (BC) risk? Results have been inconsistent. In this analysis of data from a large, prospective European study, the authors found that, overall, folate and vitamin B12 status were not clearly associated with BC risk. However, the risk did seem to increase somewhat for women who had higher vitamin B12 levels and either low plasma folate or increased alcohol consumption. The authors suggest that this may involve nutrient‐nutrient or gene‐nutrient interactions, such as changes in DNA methylation, which require further investigation.
Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk ...is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow‐up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p‐trends<0.001. Population attributable risk calculations showed that 18.8% of all GC and 62.4% of cardia GC cases could have been prevented if participants in this population had followed the healthy lifestyle behaviors of this index. Adopting several healthy lifestyle behaviors including not smoking, limiting alcohol consumption, eating a healthy diet and maintaining a normal weight is associated with a large decreased risk of GC.
What's new?
Several modifiable lifestyle factors, including smoking status, alcohol consumption, diet quality and weight, have been independently associated with gastric cancer. Behavioral patterns often cluster, however, “lifestyle scores” can be used to analyse overlapping risk factors. In this study, the authors used a “healthy‐lifestyle index” to evaluate the combined effects of all of the above factors on the risk of developing gastric cancer (GC). They found that following a healthy lifestyle dramatically decreases the burden of gastric cancer.
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