High Population Frequency of GNRHR p.Q106R in Malta: An Evaluation of Fertility and Hormone Profiles in Heterozygotes.

Context: The gonadotropin-releasing hormone receptor variant GNRHR p.Q106R (rs104893836) in homozygosity, compound heterozygosity, or single heterozygosity is often reported as the causative variant in idiopathic hypogonadotropic hypogonadism (IHH) patients with GnRH deficiency. Genotyping of a Maltese newborn cord-blood collection yielded a minor allele frequency (MAF) 10 times higher (MAF = 0.029; n = 493) than that of the global population (MAF = 0.003). Objective: To determine whether GNRHR p.Q106R in heterozygosity influences profiles of endogenous hormones belonging to the hypothalamic-pituitary axis and the onset of puberty and fertility in adult men (n = 739) and women (n = 239). Design Setting and Participants: Analysis of questionnaire data relating to puberty and fertility, genotyping of the GNRHR p.Q106R variant, and hormone profiling of a highly phenotyped Maltese adult cohort from the Maltese Acute Myocardial Infarction Study. Main Outcome and Results: Out of 978 adults, 43 GNRHR p.Q106R heterozygotes (26 men and 17 women) were identified. Hormone levels and fertility for all heterozygotes are within normal parameters except for TSH, which was lower in men 50 years or older. Conclusion: Hormone data and baseline fertility characteristics of GNRHR p.Q106R heterozygotes are comparable to those of homozygous wild-type individuals who have no reproductive problems. The heterozygous genotype alone does not impair the levels of investigated gonadotropins and sex steroid hormones or affect fertility. GNRHR p.Q106R heterozygotes who exhibit IHH characteristics must have at least another variant, probably in a different IHH gene, that drives pathogenicity. We also conclude that GNRHR p.Q106R is likely a founder variant due to its overrepresentation and prevalence in the island population of Malta.

Kounis syndrome uncovers severe coronary disease: an unusual case of acute coronary syndrome secondary to allergic coronary vasospasm.

Acute coronary syndrome occurring during the course of a type I hypersensitivity reaction constitutes Kounis syndrome. We report a case of a 64-year-old man who presented with a non-ST elevation myocardial infarction and peripheral blood eosinophilia. He had rhinitis and constitutional symptoms for several days prior to presentation. Blood investigations revealed moderate eosinophilia and elevated IgE levels. A cardiac MRI showed generalised oedema with a subtle wall motion abnormality in basal inferior/inferolateral wall, and subendocardial high signal on late gadolinium enhancement suggesting a localised myocardial infarction. A coronary angiogram then revealed triple vessel disease. A diagnosis of Kounis syndrome was made. Within days of starting appropriate treatment, the patient's eosinophil count returned to normal with improvement of clinical picture.

Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: a study among rheumatologists and patients from 44 European countries.

OBJECTIVES: To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries. METHODS: We conducted three cross-sectional surveys in 50 European countries: one on work (re-)integration and social security (SS) system arrangements in case of sick leave and long-term WD due to RA (one rheumatologist per country), and two among approximately 15 rheumatologists and 15 patients per country on perceptions regarding SS arrangements on work participation. Differences in regulations and perceptions were compared across categories defined by gross domestic product (GDP), type of social welfare regime, European Union (EU) membership and country RA WD rates. RESULTS: Forty-four (88%) countries provided data on regulations, 33 (75%) on perceptions of rheumatologists (n=539) and 34 (77%) on perceptions of patients (n=719). While large variation was observed across all regulations across countries, no relationship was found between most of regulations or income compensation and GDP, type of SS system or rates of WD. Regarding perceptions, rheumatologists in high GDP and EU-member countries felt less confident in their role in the decision process towards WD (ß=-0.5 (95% CI -0.9 to -0.2) and ß=-0.5 (95% CI -1.0 to -0.1), respectively). The Scandinavian and Bismarckian system scored best on patients' and rheumatologists' perceptions of regulations and system performance. CONCLUSIONS: There is large heterogeneity in rules and regulations of SS systems across Europe in relation to WD of patients with RA, and it cannot be explained by existing welfare regimes, EU membership or country's wealth.

The impact of passive and active smoking on inflammation, lipid profile and the risk of myocardial infarction.

OBJECTIVE: To investigate the effect of passive smoking, active smoking and smoking cessation on inflammation, lipid profile and the risk of myocardial infarction (MI). METHODS: A total of 423 cases with a first MI and 465 population controls from the Maltese Acute Myocardial Infarction (MAMI) Study were analysed. Data were collected through an interviewer-led questionnaire, and morning fasting blood samples were obtained. ORs adjusted for the conventional risk factors of MI (aORs) were calculated as an estimate of the relative risk of MI. The influence of smoking on biochemical parameters was determined among controls. RESULTS: Current smokers had a 2.7-fold (95% CI 1.7 to 4.2) and ex-smokers a 1.6-fold (95% CI 1.0 to 2.4) increased risk of MI. Risk increased with increasing pack-years and was accompanied by an increase in high-sensitivity C reactive protein levels and an abnormal lipid profile. Smoking cessation was associated with lower triglyceride levels. Exposure to passive smoking increased the risk of MI (aOR 3.2 (95% CI 1.7 to 6.3)), with the OR being higher for individuals exposed to passive smoking in a home rather than in a public setting (aOR 2.0 (95% CI 0.7 to 5.6) vs aOR 1.2 (95% CI 0.7 to 2.0)). Passive smoke exposure was associated with higher levels of total cholesterol, triglycerides and total cholesterol:high-density lipoprotein cholesterol ratio compared with individuals not exposed to passive smoking. CONCLUSIONS: Both active and passive smoking are strong risk factors for MI. This risk increased with increasing pack-years and decreased with smoking cessation. Such effects may be partly mediated through the influence of smoking on inflammation and lipid metabolism.

Benign cystic mediastinal teratoma presenting as a massive pleural effusion in a 17-year-old boy.

Mediastinal teratomas are a rare, albeit an important differential diagnosis of anterior/middle mediastinal masses in young adults and various atypical presentations have been reported. The authors report a case of a 17-year-old boy who presented with a 2-month history of worsening shortness of breath and pleuritic chest pain. A massive left-sided pleural fluid collection was seen on a chest radiograph (CXR). The pleural fluid was drained and a CT Thorax confirmed the presence of a cystic mass. Following re-accumulation of the fluid, thoracotomy was performed and a benign mediastinal teratoma excised. The patient remained well with no evidence of recurrence on follow-up CXRs a year post operatively.

Empyema Secondary to Actinomyces meyeri Treated Successfully with Ceftriaxone Followed by Doxycycline.

Actinomycosis is a relatively rare infection caused by Gram-positive bacteria. We present the case of a 54-year-old, previously healthy, male patient with a history of severe penicillin allergy who developed severe pneumonia and empyema caused by Actinomyces meyeri. Presenting symptoms included productive cough, right upper quadrant pain, and chills and rigors. He required drainage of the empyema via tube and prolonged antibiotic treatment with intravenous ceftriaxone for 2 weeks followed by oral doxycycline for 6 months.