Persisting Symptomatic Severe Secondary Mitral Regurgitation in Heart Failure Patients.

Aims We aimed to assess the rate of persisting severe symptomatic secondary mitral regurgitation (MR) in a newly diagnosed heart failure (HF) population following optimisation of guideline directed medical therapy (GDMT), cardiac resynchronisation therapy (CRT) and revascularisation. Methods We assessed all new patients referred to our hospital group's HF clinics. We retrospectively reviewed these patients at HF clinic enrolment, HF programme completion, as well as most recent follow up. Results Of the 242 new patients referred to our HF clinics, there were 10 patients (4.1%) who had either persisting symptomatic severe secondary MR at HF programme completion, or had undergone mitral valve surgery. There were no percutaneous mitral valve repairs at the time of these patients' referrals. The rates of ACE/ARB/ARNI, BB and MRA use were 87.8%, 94.1%, and 49.8% in those with mid ranged, or reduced ejection fraction. The rates of ICD and CRT therapy were 15.1% and 4.4% at follow up. Patients with severe MR had higher time adjusted rates of death or hospitalization for heart failure. Conclusion In a well-treated newly diagnosed HF population, repeat assessment at HF programme completion suggests 4.1% of patients have a persisting indication for percutaneous mitral valve repair based on persisting severe symptomatic secondary MR.

A Review of a Tertiary Referral Centre's CT Coronary Angiography Programme.

Aims To investigate the implication of outpatient CT coronary angiogram (CTCA) waiting times on patient outcomes and service provision. Methods All outpatient CTCAs requested for stable chest pain during 2017 in our catchment area were included. Rate of major adverse cardiovascular events (MACE), presentations with chest pain to the emergency department (ED), cardiology outpatient attendance, time interval in alteration of Coronary artery disease (CAD) prognostic treatment, rate of angiography and percutaneous coronary intervention (PCI) were noted. Results 172 CTCAs were included. 11 (6.4%) presented to ED with chest pain. 38 (22.1%) attended outpatients prior to scan completion. 17 (9.9%) required alteration of prognostic treatment, taking on average 10.4 (+/-4.5) months to occur. 21 (12.2%) underwent coronary angiography and 7 (4.1%) had PCI, which took on average 9.9 (+/-6.6) months. One non-fatal MI requiring CABG was noted. Conclusion The low rate of MACE and revascularisation likely represents appropriately low risk patient selection for CTCA. Presentation to clinic prior to scan completion highlights a need for better administration support.

PTTG1IP and MAML3, novel genomewide association study genes for severity of hyperresponsiveness in adult asthma.

BACKGROUND: The severity of bronchial hyperresponsiveness (BHR) is a fundamental feature of asthma. The severity of BHR varies between asthmatics and is associated with lack of asthma control. The mechanisms underlying this trait are still unclear. This study aimed to identify genes associated with BHR severity, using a genomewide association study (GWAS) on the slope of BHR in adult asthmatics. METHODS: We performed a GWAS on BHR severity in adult asthmatics from the Dutch Asthma GWAS cohort (n = 650), adjusting for smoking and inhaled corticosteroid use, and verified results in three other cohorts. Furthermore, we performed eQTL and co-expression analyses in lung tissue. RESULTS: In the discovery cohort, one genomewide significant hit located in phosphodiesterase 4D, cAMP-specif (PDE4D) and 26 SNPs with P-values < 1*10-5 were found. None of our findings replicated in adult and childhood replication cohorts jointly. In adult cohorts separately, rs1344110 in pituitary tumour-transforming 1 interacting protein (PTTG1IP) and rs345983 in Mastermind-like 3 (MAML3) replicated nominally; minor alleles of rs345983 and rs1344110 were associated with less severe BHR and higher lung tissue gene expression. PTTG1IP showed significant co-expression with pituitary tumour-transforming 1, the binding factor of PTTG1lP, and with vimentin and E-cadherin1. MAML3 co-expressed significantly with Mastermind-like 2 (MAML2), both involved in Notch signalling. CONCLUSIONS: PTTG1IP and MAML3 are associated with BHR severity in adult asthma. The relevance of these genes is supported by the eQTL analyses and co-expression of PTTG1lP with vimentin and E-cadherin1, and MAML3 with MAML2.

Opisthorchis felineus negatively associates with skin test reactivity in Russia-EuroPrevall-International Cooperation study.

BACKGROUND: Most studies on the relationship between helminth infections and atopic disorders have been conducted in (sub)tropical developing countries where exposure to multiple parasites and lifestyle can confound the relationship. We aimed to study the relationship between infection with the fish-borne helminth Opishorchis felineus and specific IgE, skin prick testing, and atopic symptoms in Western Siberia, with lifestyle and hygiene standards of a developed country. METHODS: Schoolchildren aged 7-11 years were sampled from one urban and two rural regions. Skin prick tests (SPT) and specific IgE (sIgE) against food and aeroallergens were measured, and data on allergic symptoms and on demographic and socioeconomic factors were collected by questionnaire. Diagnosis of opisthorchiasis was based on PCR performed on stool samples. RESULTS: Of the 732 children included, 34.9% had opisthorchiasis. The sensitization to any allergen when estimated by positive SPT was 12.8%, while much higher, 24.0%, when measured by sIgE. Atopic symptoms in the past year (flexural eczema and/or rhinoconjunctivitis) were reported in 12.4% of the children. SPT was positively related to flexural eczema and rhinoconjunctivitis, but not to wheezing. Opisthorchiasis showed association with lower SPT response, as well as borderline association with low IgE reactivity to any allergen. However, the effect of opisthorchiasis on SPT response was not mediated by IgE, suggesting that opisthorchiasis influences SPT response through another mechanism. Opisthorchiasis also showed borderline association with lower atopic symptoms. CONCLUSIONS: There is a negative association between a chronic helminth infection and skin prick test reactivity even in a developed country.

Age at Menarche and Time Spent in Education: A Mendelian Randomization Study.

Menarche signifies the primary event in female puberty and is associated with changes in self-identity. It is not clear whether earlier puberty causes girls to spend less time in education. Observational studies on this topic are likely to be affected by confounding environmental factors. The Mendelian randomization (MR) approach addresses these issues by using genetic variants (such as single nucleotide polymorphisms, SNPs) as proxies for the risk factor of interest. We use this technique to explore whether there is a causal effect of age at menarche on time spent in education. Instruments and SNP-age at menarche estimates are identified from a Genome Wide Association Study (GWAS) meta-analysis of 182,416 women of European descent. The effects of instruments on time spent in education are estimated using a GWAS meta-analysis of 118,443 women performed by the Social Science Genetic Association Consortium (SSGAC). In our main analysis, we demonstrate a small but statistically significant causal effect of age at menarche on time spent in education: a 1 year increase in age at menarche is associated with 0.14 years (53 days) increase in time spent in education (95% CI 0.10-0.21 years, p = 3.5 × 10-8). The causal effect is confirmed in sensitivity analyses. In identifying this positive causal effect of age at menarche on time spent in education, we offer further insight into the social effects of puberty in girls.

The locus C11orf30 increases susceptibility to poly-sensitization.

A number of genetic variants have been associated with allergic sensitization, but whether these are allergen specific or increase susceptibility to poly-sensitization is unknown. Using data from the large multicentre population-based European Community Respiratory Health Survey, we assessed the association between 10 loci and specific IgE and skin prick tests to individual allergens and poly-sensitization. We found that the 10 loci associate with sensitization to different allergens in a nonspecific manner and that one in particular, C11orf30-rs2155219, doubles the risk of poly-sensitization (specific IgE/4 allergens: OR = 1.81, 95% CI 0.80-4.24; skin prick test/4+ allergens: OR = 2.27, 95% CI 1.34-3.95). The association of rs2155219 with higher levels of expression of C11orf30, which may be involved in transcription repression of interferon-stimulated genes, and its association with sensitization to multiple allergens suggest that this locus is highly relevant for atopy.

[Analysis of a case series of workers with mobbing syndrome]. / Analisi di una casistica di lavoratori con patologia da mobbing.

Mobbing represents nowadays a major challenge for Occupational Medicine. We examined, during the last seven years, 253 patients who asked medical assistance for psychopathological problems by them ascribed to mobbing in the working environment. All patients underwent occupational health visit, psychological counselling (including personality tests administration), and psychiatric evaluation. A clinical picture probably due to mobbing was diagnosed in 37 workers: 2 cases of Post-Traumatic Stress Disorder (PTSD), 33 of Adjustment Disorder (AD), and 2 of anxiety disorder. Regarding mobbing typology, we found 19 cases of vertical mobbing (by an employer/manager to employees), 14 cases of strategic mobbing, 3 cases of horizontal mobbing (among colleagues), and one non intentional mobbing. In conclusion, a pure mobbing syndrome was diagnosed in a lower proportion than that reported by other investigators. The described interdisciplinary approach appears useful for the diagnostic assessment of suspect mobbing cases, that in turn is crucial for prognosis and treatment, as well as in relation to medico-legal issues and work-related compensation claims.

[Ergonomy and videoterminals]. / Ergonomia e videoterminali.

After defining some concepts relative to ergonomy and videoterminals (VDT), the paper describes the main health risks for VDT workers (visual, muscle-skeletal and stress disorders). The ergonomic requirements established by the Italian legislation for VDT work are then examined, including illumination, the working environment, the working desk and seat, the video-screen, the keyboard, the upper body position, pauses and physical exercise, training and information. Recent regulations (in particular the law 422/2000) on the sanitary surveillance of VDT workers are finally reported.

[Occupational risks among public safety and security forces]. / Rischi professionali nelle Forze dell'Ordine.

The present paper tries to identify the occupational risk factors (physical, chemical, biological, psychological), variable depending on jobs and tasks, to which the heterogeneous public safety/security workers are exposed. The fight against criminality and public order maintenance imply (sometimes fatal) traumatic risks, and expose to psychophysical and sensorial tiring, unfavourable macro- and microclimatic conditions, the risk of baropathy (air navigation, underwater activities), noise (generated by firearms and several other sources), vibrations and shakings (automatic weapons, transport vehicles), the risk of electric injury, ionizing (X and gamma rays) and non-inonizing (ultraviolet rays, microwaves and radiofrequencies, electromagnetic fields) radiations. Chemical hazards include carbon monoxide and other combustion products (fires, urban traffic), substances released in chemical accidents, tear gases, lead (firing grounds, metal works, environmental pollution), solvents, lubrificants and cutting oils (mechanic repair and maintenance), laboratory materials and reagents, irritant and/or sensitizing agents contained in gloves. The main biological risks are tetanus, blood-borne diseases (viral hepatitis, AIDS), aerogenous diseases (e.g., tuberculosis, Legionnaire's disease, epidemic cerebrospinal meningitis), dog- or horse-transmitted zoonosis. Finally, emotional, psychosomatic and behavioural stress-related disorders (e.g., burn-out syndrome, post-traumatic stress disorder) are typically frequent. The presence of numerous and diversified hazards among public safety/security forces imposes the adoption of occupational medicine measures, including risk assessment, health education, technical and environmental prevention, personal protective devices, sanitary surveillance and biological monitoring, clinical interventions (diagnosis, therapy and rehabilitation of occupational accidents and illnesses), prompt medico-legal evaluation of occupational-related compensation claims.

Clinical trial with muzolimine in healthy and hypertensive subjects: new vistas on the drug action.

The mechanism of muzolimine (3-amino-1-[3,4-dichloro-alpha-methyl-benzyl]-2 pyrazolin-5-one) action is still not completely defined. The identified site of action is the Henle loop, similarly to furosemide which acts also by mediating renal prostaglandin synthesis. The aim of the present study was to evaluate the early effects of muzolimine (30 mg per os) on renal function and prostaglandin urinary excretion in healthy controls and hypertensive subjects. Urinary flow reached the peak values by the third hour after the drug and a diuretic effect not directly dependent on glomerular filtration was observed, especially in hypertensive patients. In these cases the diuresis increased also due to a low glomerular filtration rate and tubular phenomena were more evident than in controls: an increasing Na+ tubular excretion and a parallel decreasing % Na+ reabsorption. Blood pressure was not significantly influenced by muzolimine in healthy subjects, while it returned to normal values in the hypertensive group. A cyclooxigenase inhibitor, lysine acetylsalicylate (1 g i.m.) administered 10 minutes after muzolimine, was not able to modify the parameters under consideration. Therefore a mediation by prostaglandins on the diuretic and antihypertensive effects of the drug under study may probably be excluded.

Spectral fluorescence of direct anterior restorative materials.

The fluorescent characteristics of silicate cements, acrylic resins, and composite resins and all anterior restorative materials have been compared with the natural teeth when specimens were submitted to ultra-violet radiation. The effect of glazes on composite resins and of discolouration from ultra-violet radiation on composites and acrylic resins is to reduce the amount of fluorescence of the former and to change the quality of the fluorescence.

Silicotuberculosis in the elderly: report of two cases.

Silicotuberculosis is observed rarely in the current clinical practice. We present two patients (a 72-year-old man and a 84-year-old woman) who developed silicosis after having worked for several decades in the ceramics industry. In both, pulmonary tuberculosis complicated the clinical picture several years after retirement. The first subject presented a multicavitary lesion in the apex of the right lung, which subsequently evolved with fibrosis. The other developed bilateral tubercular bronchopneumonia and right tubercular pleurisy, that improved after prolonged antimycobacterial polychemotherapy. The two cases confirm that patients with silicosis are at an increased risk of developing tuberculosis, and show that, nowadays, silicotuberculosis may represent a geriatric problem. In the elderly, recognition of tuberculosis associated with silicosis is often difficult. Occupational history, radiology (conventional chest radiography and computed tomography) and microbiology (identification of Mycobacterium tuberculosis in sputum and pleural exudate) are helpful for the correct diagnosis, which, in turn, is important for prognosis and treatment, as well as in relation to medico-legal issues and occupational-related compensation claims.

[A case of complete section of the pancreas during closed abdominal trauma]. / Caso di sezione completa del pancreas in corso di trauma chiuso dell'addome.

A review of the literature on pancreatic trauma and its treatment in the light of recent experience is presented. The incidence, mechanism, classification, diagnosis, treatment and complications of pancreatic trauma are discussed. A case of pancreatic transection after blunt abdominal trauma is described.

[Proposal for an outline to be used in the assessment of chemical risk according to the legislative decree 25/20002]. / Proposta di uno schema utilizzabile per la valutazione del rischio chimico ai sensi del decreto legislativo 25/2002.

We present an operative outline for the evaluation of chemical risk in the work environment, according to the legislative decree 25/2002. It includes the following points: identificative data of the company, scope and field of application, description of the working activities, preventive and protective measures, medical report (including biological monitoring), environmental monitoring, conclusive evaluation. The scheme is a quali-quantitative instrument for the employer and his collaborators to establish whether the chemical risk present in the single productive sites can be considered "moderate" or "not moderate".

[Disability and occupational medicine: definitions, scope, and operative examples]. / Disabilità e medicina del lavoro: definizioni, ambiti, esempi operativi.

2003 is the year of disability. This paper briefly illustrates the multiform relationships between occupational medicine and disability, discussing the complex legislation on this matter. A historiographic account is presented of the image of the disabled individual through the centuries. The main terms regarding disability are defined according to current legislation. Current Italian laws are difficult to interpret and to be put into effect. In this process, the occupational physician may be asked to perform several duties, including diagnosis and certification, fitting the disabled to work, safeguarding his/her moral and legislative rights, prevention and sanitary surveillance. Some professional experiences of the authors (regarding certification of the working capability, medico-legal recognition, and adaptation to work) are finally presented.

[Mobbing: analysis of an ambulatory case load]. / Mobbing: analisi di una casistica ambulatoriale.

We present twenty outpatients (11 males; 9 females) who asked medical assistance, during the last two years, for psychopathological problems by them ascribed to "mobbing" in the work environment. Six subjects were employed in public institutions, 14 in private companies. All patients underwent occupational health specialistic visit, psychological counselling (including personality tests administration), and psychiatric evaluation. A psychopathological picture reasonably correlable to "mobbing" was diagnosed in four subjects only (20% of the cases), i.e. in a lower proportion than that reported by other investigators.

Exploring the causes of cutaneous B-cell lymphoma: we should learn from the Lyme disease experience.

Epidemiological studies rely on the uneven distribution of disease within and between populations and represent a simple but efficient way of studying disease causation. The incidence of non-Hodgkin's lymphomas (NHLs) has increased dramatically over the past few decades and the epidemic calls for epidemiological studies. The study of Munksgaard and colleagues, in this issue of Dermatology, is a good example of an epidemiological study based on the so-called ecological correlation. It focuses on cutaneous B-cell lymphoma (CBCL) and fails to document a correlation between CBCL incidence and Lyme disease as a surrogate indicator for the exposure to tick bites. Although ecological studies neither inform about the time relationship between exposure and disease nor usually allow control for confounding variables, they can provide important information that would guide the direction of further research. There is a number of analytical studies focusing on risk factors for NHLs. One drawback of these studies is that they consider NHLs as a single category. One merit of the paper of Munksgaard et al. is that it focused on a rather specific disease, i.e. CBCL.

[Structural changes in composite resins identified using Lugol's solution]. / Alteraçoes estruturais nas resinas compostas: identificaçao por meio de soluçao de Lugol.

The authors studied the staining of specimens of composite resins, when they were immersed in Lugol solution. In this study, we related chemical and photo-activated resins, and the estructure modifications were analysed in relation to the consulted bibliography. The use of Lugol solution showed a practical way to identify the possible modifications in the polymeric structure of the composite resins.

Measuring complexity/level of care and appropriateness of resource use in intensive care units.

BACKGROUND: Throughout the world, the cost of critical care medicine is increasing more than the overall health care cost. Thus, a higher attention to improve the efficiency of the use of ICU resources is indispensable. The objective of this study was the development of a simple and reliable tool for the evaluation of the appropriateness of ICU utilization. DESIGN: A repeated cross-sectional data collection was performed twice a week, during a 61-day study period. SETTING: Twenty-three Italian general ICUs. PATIENTS: All patients present in the 23 ICUs on the 17 index days. INTERVENTIONS: On each index day, patients were checked for receiving ventilation/CPAP, pulmonary arterial pressure monitoring, intracranial pressure monitoring, vaso-active drug infusion and hemodialysis-ultrafiltration. Simultaneously, each ICU bed was assessed for its technical and personnel facilities in order to estimate the deliverable level of care. RESULTS: A total of 1250 patients were studied, for a total number of 7533 patient-days. The overall occupancy rate per ICU was 83.8% (-range: 54.4% to 96.1%). The high-level occupancy rate (rate of patients requiring high level of care and actually occupying high-facility beds) was 69.4% (range: 25.0% to 149.0%), while the corresponding low-level occupancy rate was 101.1% (range: 31.3% to 329.4%). CONCLUSIONS: Our model clearly showed up a certain degree of inappropriateness in the use of ICU resources. Most of the ICUs (69.6%) used a very large proportion of their high-facility beds for patients who did not need high-level care. Being very simple, our method could represent a useful tool for continuous evaluation of the appropriateness of resource utilization in the ICU.