An overview of molecular mechanisms in fabry disease

Fabry disease (FD) (OMIM #301500) is a rare genetic lysosomal storage disorder (LSD). LSDs are characterized by inappropriate lipid accumulation in lysosomes due to specific enzyme deficiencies. In FD, the defective enzyme is alpha-galactosidase A (alpha-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death. The increasing understanding of FD, and LSD in general, has led in recent years to the introduction of enzyme replacement therapy (ERT), which aims to slow, if not halt, the progression of the metabolic disorder. In this review, we provide an overview of the main features of FD, focusing on its molecular mechanism and the role of biomarkers

A Case of Advanced Tubal Ectopic Pregnancy after Emergency Contraception

Ectopic pregnancy is a relatively common condition and an important cause of morbidity in women of childbearing age. The most frequent implantation site is the fallopian tube. Most cases are diagnosed in an early gestational period. Patients come to the attention of clinicians for pelvic pain and vaginal blood loss, and consequent diagnosis is made through clinical presentation, laboratory tests, and ultrasound. Other rarer implantation sites such as the abdominal cavity give space for ectopic pregnancy to grow until later gestational ages, delaying diagnosis. This is a rare case of a healthy 41-year-old woman with an advanced ectopic pregnancy after emergency contraception with Ulipristal Acetate. The patient went to visit for amenorrhea after taking a contraceptive. Evaluation with ultrasound demonstrated a 10 + 4 weeks’ unruptured tubal pregnancy with fetal heart rate. The patient underwent laparoscopic salpingectomy without complication. This is the first case of such an advanced ectopic pregnancy in a woman who performed emergency contraception with Ulipristal Acetate

Incidence of gallstone disease in Italy: Results from a multicenter, population-based Italian study (the MICOL project)

AIM: To evaluate gallstone incidence and risk factors in a large population-based study

Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: comparison with Child-Pugh score and serum bile acid levels

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients

Pathophysiology, Functional Assessment and Prognostic Implications of Nutritional Disorders in Systemic Amyloidosis

Gastrointestinal involvement is a common clinical feature of patients with systemic amyloidosis. This condition is responsible for invalidating gastrointestinal symptoms, a significant macro and micronutrient deficit, and is a marker of disease severity. Gastrointestinal involvement should be actively sought in patients with systemic amyloidosis, while its diagnosis is challenging in patients with isolated gastrointestinal symptoms. The nutritional status in systemic amyloidosis plays an essential role in the clinical course and is considered a significant prognostic factor. However, the definition of nutritional status is still challenging due to the lack of internationally accepted thresholds for anthropometric and biochemical variables, especially in specific populations such as those with systemic amyloidosis. This review aims to elucidate the fundamental steps for nutritional assessment by using clinical and instrumental tools for better prognostic stratification and patient management regarding quality of life and outcomes

Occupational injuries and sickness absence: association with job demand, decision latitude, and 1 re style in 2174 workers in the Veneto Region

Abstract BACKGROUND: Stress was the most frequent (26,9%) health problem reported in a survey on the perception of working and health conditions in 5000 workers in the Veneto Region. OBJECTIVES: The aim of the study was to investigate in the Veneto Region the association between occupational stress and events occurred in the previous 12 months: occupational accidents, or sickness absence for 10 or more consecutive days. METHODS: Perceived occupational stress is correlated, according to Karasek's model, to high job demand (JD) and low decision latitude (DL). Using Karasek's questionnaire (to which questions on smoking and alcohol consumption were added), we examined 2174 subjects working in 30 companies with between 10 and 500 employees, who belonged to the occupational categories of industry and services that are more prevalent in the Veneto Region. The questionnaire was administered by the occupational physician during health surveillance. The subjects were classified on the basis of current exposure to psychosocial factors or, for subjects reporting an event, their exposure at that time. We identified the tertiles of JD and DL; data were submitted to the analysis of multiple logistic regression, estimating odds ratio (OR) and 95% confidence interval (CI). The population attributable risk (PAR) was calculated using the formula (pc (OR-1)/OR), where pc is the fraction of exposed cases. RESULTS: An elevated risk of occupational accidents was found in subjects with regular consumption of alcohol (OR = 2.0; IC = 1.2-3.5), in smokers smoking 10-20 (2.3; 1.3-3.8) or >20 cigarettes/day (3.8; 1.8-7.9), in the highest tertile of JD (2.29; 1.35-3.89) and in the lowest tertile of DL (1.6; 1.0-2.6). PAR was 37.6% for occupational factors (high JD and low DL), 44.5%for non-occupational factors (cigarette smoking and alcohol consumption), and 82.1% overall. The risk of sickness absence increased in subjects smoking 10-20 cigarettes (1.63 = 1.1-2.40), in the highest tertile of JD (1.5; 1.0-2.2) and in the lowest tertile of DL (1.6; 1.1-2.2). PAR was 26.1% for occupational factors (high JD and low DL), 7.6% for non-occupational factors (smoking), and 30.4% overall. While the risk of sick absence increased mainly with the reduction of DL, the risk of occupational accidents increased with increasing JD and, to a lesser extent, with decreasing DL. The current approach to accident prevention is based only on technical and administrative aspects, in spite of the fact that 80% of accidents are not attributable to malfunctioning of machinery. Injury prevention should address technical, personal and psychosocial risk factors together as a whole

Multidrug-resistant Gram-negative post-neurosurgical meningitis and the role of intraventricular colistin: a case series

: The aim of this study was to report the clinical experience of intraventricular colistin for the treatment of multi-resistant Gram-negative post-surgical meningitis in a tertiary hospital. Post-neurosurgical meningitis (PNM) is one of the life-threatening complications of neurosurgical procedures, and is frequently sustained by Acinetobacter baumannii and Klebsiella pneumoniae. Here we describe our experience of five cases of PNM caused by gram-negative multi-drug resistant (MDR) bacteria, treated with intraventricular (IVT) colistin, admitted to the Neurosurgery Unit of A.R.N.A.S. Civico of Palermo, Italy, from January 2016 to June 2020. In four patients the cerebrospinal fluid (CSF) culture was positive for A. baumannii, while in one patient it was positive for K. pneumoniae. IVT colistin therapy was administered for a median time of 18 days (range 7-29). The median time to CSF negativization was seven days (range 5-29). IVT colistin administration was associated with intravenous administration of meropenem and colistin in all patients. As regards clinical outcome, four patients were successfully treated and were subsequently discharged, while one patient died following respiratory complications and subsequent brain death. IVT colistin administration is an effective therapy for MDR post-neurosurgical meningitis and its administration is also prescribed by guidelines. However, IVT therapy for Gram-negative ventriculitis is mostly understudied. Our paper adds evidence for such treatment that can actually be considered life-saving

Indagine pilota conoscitiva sulle condizioni di salute e sicurezza negli ambienti di lavoro relativa ad una realt\ue0\ua0 regionale: Veneto

L'Agenzia Europea per la Sicurezza e la salute sul Lavoro analizza periodicamente i principali problemi di salute dei lavoratori attraverso i dati provenienti da indagini condotte nei vari Paesi della U.E, ed allo scopo ha attivato un Osservatorio dei rischi. L'obiettivo della presente ricerca, promossa dall'ISPESL in collaborazione con la Direzione per la Prevenzione del Veneto, \ue8 stato quello di sperimentare un modello di monitoraggio da riproporre per un\u2019indagine mirata su scala europea. Immagine di copertina della pubblicazione La ricerca ha permesso di studiare i rischi professionali ed i problemi di salute prevalenti percepiti dai lavoratori di una regione europea altamente industrializzata quale il Veneto. Dalla ricerca emerge che le principali problematiche di salute sono in primo luogo lo stress (26.9%), seguito dal mal di schiena (17.8%) e dal dolore agli arti (11.1%). Anche nell\u2019indagine condotta nel 2000 in ambito europeo da Eurofound (European Foundation for the Improvement of Living and Working Conditions), lo stress \ue8 risultato essere uno tra i principali problemi di salute, secondo solo al mal di schiena. In merito ai fattori di rischio percepiti, accanto a quelli tradizionali di tipo fisico-chimico (vibrazioni, rumore, inalazione di vapori fumi, polveri, sostanze pericolose), sono stati evidenziati aspetti delle condizioni di lavoro quali: posture, movimentazione carichi, movimenti ripetitivi, turni, eccessive richieste sul piano psichico e cognitivo. La diffusione e gli effetti dello stress negli ambienti di lavoro \ue8 stata quindi indagata mediante il questionario di Karasek: la frequenza di high strain (ovvero la percezione di vivere una condizione lavorativa caratterizzata da elevata domanda insieme a un basso controllo sul compito) \ue8 pari al 26.6% del campione. Il rischio di high strain \ue8 risultato essere maggiore nelle donne rispetto ai maschi, nei soggetti che consumano psicofarmaci rispetto a coloro che non ne fanno uso, nei non-fumatori rispetto ai fumatori, mentre non vi sono differenze rispetto all\u2019et\ue0, alla scolarit\ue0, al Paese di origine, e al consumo di alcol. I pi\uf9 elevati rischi di stress sono stati riferiti dagli addetti del commercio e del comparto socio-sanitario, nei soggetti con pi\uf9 di 10 anni di anzianit\ue0 nella mansione e nei lavoratori che avevano riferito un infortunio sul lavoro o un\u2019assenza per motivi di salute. L\u2019analisi dei dati INPS sulle assenze dal lavoro per malattia certificate nel periodo 1997-2002 evidenzia una percentuale di assenze pi\uf9 bassa nei comparti dell\u2019Artigianato rispetto a quelli dell\u2019Industria e del Terziario, sempre inferiore negli operai rispetto agli impiegati e con un picco nella classe d\u2019et\ue0 \u201c20-29 anni\u201d. Il sesso femminile mostra una maggiore tendenza dei colleghi maschi ad \u201cammalare\u201d: il tasso d\u2019incidenza (eventi/assicurati) esaminato evidenzia una netta disuguaglianza tra i due sessi, molto alta in particolare nell\u2019Industria. L\u2019analisi dei tassi di inabilit\ue0/invalidit\ue0 lavorativa INPS dal 1994 al 2002 evidenzia che il rischio di invalidit\ue0 \ue8 significativamente maggiore nei lavoratori dipendenti dell\u2019Artigianato, Industria e Terziario che nei lavoratori autonomi. I comparti a maggiore rischio di invalidit\ue0 INPS sono risultati essere l\u2019Edilizia e l\u2019Impiantistica (sia di tipo industriale che artigianale), seguita dal Tessile (come attivit\ue0 industriale). Infine, l\u2019analisi dei tassi standardizzati per et\ue0 e sesso di invalidit\ue0/inabilit\ue0, assenze dal lavoro per malattia e infortuni sul lavoro nei lavoratori dell\u2019Industria dal 1994 al 2002 evidenzia una riduzione del tasso di inabilit\ue0/invalidit\ue0, una tendenza alla riduzione negli anni pi\uf9 recenti del tasso di assenze per malattia (dopo un aumento sino al 1999), e infine un aumento del tasso di infortuni sul lavoro (in discesa nel 2002), che potrebbe essere dovuto all\u2019incremento di lavoratori extracomunitari nelle fabbriche e/o al riconoscimento degli infortuni in itinere a partire dal 2000 per effetto dei cambiamenti normativi Inail. In conclusione, la sperimentazione da parte dell\u2019Ispesl, con la collaborazione della regione Veneto, di un sistema di monitoraggio basato sia su dati rilevati correntemente per scopi di tutela che su dati raccolti attraverso specifiche indagini ha portato a potenziare il patrimonio informativo attinente la salute dei lavoratori. Nella regione pilota l\u2019indagine ha consentito di: fornire un know-how per un\u2019indagine che stabilisca le priorit\ue0 di intervento relative a settori, attivit\ue0 professionali, aree, gruppi a rischio, ecc.; creare le basi per un modello di monitoraggio della salute e della sicurezza a livello nazionale riproponibile in ambito europeo; individuare e valutare i parametri per la misurazione dell'adeguatezza e della qualit\ue0 degli interventi preventivi sanitari