Factors affecting long-term changes of liver stiffness in direct-acting anti-hepatitis C virus therapy: A multicentre prospective study

The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicentre prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centres; they underwent clinical, biochemical, ultrasound and transient elastography evaluations before treatment (T0), 12 weeks (SVR12) and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 vs 11.1 kPa, p = .002), with a progressive reduction until T24 (8.7 kPa, p < .001). However, only patients with steatosis and those who developed HCC did not experience a late improvement in LS. Multivariate analysis of baseline and follow-up variables identified steatosis as the only independent predictor of failure of LS improvement (OR 1.802, p = .013). ROC curve analysis of the association of LS with the risk of developing HCC showed that SVR12 ≥14.0 kPa had the highest accuracy (sensitivity 82%, specificity 99%; AUC: 0.774). Multivariate analysis revealed that LS was the only variable independently associated with an increased risk of developing HCC (OR 6.470, p = .035). Achieving an SVR was associated with a progressive, long-term decline of LS, suggesting a late improvement in liver fibrosis, besides the resolution of inflammation. Fatty liver and the development of HCC interfered with late reduction of LS. Patients with an LS ≥14 kPa at 12 weeks after the end of treatment were at higher risk for developing HCC.     

Serum testosterone levels and arterial blood pressure in the elderly.

The aim of this study was to evaluate the relationship between serum testosterone levels and arterial blood pressure (BP) in the elderly. We studied 356 non-diabetic, non-smoking, non-obese men aged 60 to 80 years and untreated for hypertension. All subjects were evaluated in the morning after an overnight fast. Evaluation included measurements of the following: BP (by mercury sphygmomanometer, Korotkoff I and V), body weight, height and free testosterone (T) plasma levels (by radioimmunoassay). According to the BP values, the subjects were classified as normotensives (NT; n=112; SBP/DBP<140/90 mmHg), systolic and diastolic hypertensives (HT; n=127; SBP/DBP>140/90 mmHg), and isolated systolic hypertensives (ISH; n=117; SBP>140 mmHg and DBP<90 mmHg). T values decreased with increasing age in all 3 groups and was significantly lower in HT (-15%) and ISH men (-21%) than in NT men (p<0.05). In each group, the T levels showed a highly significant negative correlation with BMI (p<0.001). A significant negative correlation was also found between T levels and SBP in NT (r=-0.35, p<0.001), ISH (r=-0.67, p<0.001), and HT (r=-0.19, p<0.05) men, whereas a negative correlation with DBP was observed only in the NT men (r=-0.19, p<0.05). Adjusting for the BMI confirmed a significant difference in plasma T levels between ISH and NT men, but not between HT and NT men. Multiple regression analysis employing BP as a dependent variable confirmed a strong relationship between T levels and SBP in all 3 groups, whereas a significant relationship between T levels and DBP was found only in NT men. In conclusion, although further studies are needed to clarify the relationship between plasma T levels and BP, our findings suggest that in elderly men with ISH, the reduced plasma levels of testosterone might contribute to the increased arterial stiffness typical of these subjects.     

Toxins and colonization factor antigens of enterotoxigenic Escherichia coli among residents of Jakarta, Indonesia

Infection caused by enterotoxigenic Escherichia coli (ETEC) poses a serious health problem among children and adults in developing countries. Colonization of the small intestinal mucosa by ETEC strains is mediated by antigenically specific fimbriae, also known as colonization factor antigens (CFA). The significance of this study arises from reports that active and passive immunization with ETEC strains harboring CFAs has previously been shown to induce protective immunity against diarrhea in animal models. The aim of this study was to determine toxin-associated CFAs of ETEC isolated from a diarrheal disease case-control study in Jakarta, Indonesia. Thirteen hundred and twenty-three diarrheic and control patients with lactose-fermenting colonies were screened by ganglioside GM1-enzyme-linked immunosorbent assay (GM1-ELISA) for heat-labile (LT) and heat-stable (ST) toxins. Two hundred and forty-six (19%) ETEC isolates identified by GM1-ELISA for the LT/ST toxins were screened for CFAs by Dot blot assay using monoclonal antibodies against CFA/I, II, and IV and against the putative colonization antigens (PCF) PCFO159, PCFO166, CS7, and CS17. Of the 246 ETEC isolates, 177 (72%) elaborated ST, 56 (23%) produced LT, while 13 (5%) elicited both the ST and LT toxins. CFA testing of the 246 ETEC isolates showed that 21 (8%) expressed CFA/I, 3 (1%) exhibited CFA/II, 14 (6%) elaborated CFA/IV, while 7 (3%) expressed PCFO159 and PCFO159 plus CS5. No CFAs or PCFs could be associated with 201 (82%) of the ETEC strains. This report documents the types of CFAs associated with ETEC strains in Jakarta, Indonesia. These data may help current research efforts on the development of CFA-based vaccines for humans against ETEC and provide additional information for future ETEC vaccine trials in Southeast Asia.     

Impact of the earthquake of September 26, 1997 in Umbria, Italy on the socioenvironmental and psychophysical conditions of an elderly population

The consequences of natural disasters on the social and health status of older people have not been deeply considered. The aim of this study was to evaluate the socioenvironmental and psychophysical conditions of an elderly population after a devastating earthquake. A randomly selected group of 332 older people (> or =64 years) was selected among 1548 eligible subjects living in the city of Nocera Umbra four months after an earthquake of 5.6 magnitude on the Richter scale. Three geriatricians evaluated the study subjects by means of a structured interview, and standardized scales, which considered physical and mental status, mood and anxiety, and self-perception of well-being, as well as the characteristics of family composition and social interactions. Of the study subjects, 11.1% lived alone, and 33.4% with the spouse only. Most were self-sufficient in the basic activities of daily life. Musculoskeletal diseases and hypertension were the most frequently observed pathologies in this geriatric population. In addition, 47.9% of the subjects lived in temporary houses; this group more frequently suffered from hypertension, and had a higher score of comorbidity as measured by Cumulative Illness Rating Scale (CIRS) compared to people who remained at home. People living in the pre-fabricated huts also showed a higher score on the Geriatric Depression Scale and the Hamilton scale for anxiety, and complained more often of their health status, evaluated as self-perception of well-being, when compared to the home dwellers. Although all the studied subjects suffered from the discomforts caused by the earthquake, the precariousness of living in temporary houses, whose structural characteristics do not take the needs of elderly subjects into account, could justify the higher distress experienced by persons housed in the huts. These observations suggest that, after natural disasters, emergency programs should be more adapted to elderly people, whose needs and expectations are often different from those of young adults.     

Relationship of Interleukin-12 and Interleukin-13 imbalance with class-specific rheumatoid factors and anticardiolipin antibodies in systemic lupus erythematosus

 The aim of the study was to evaluate whether the imbalance between IL-12 and IL-13 serum levels, reflecting Th1/Th2 activity, is related to class-specific circulating rheumatoid factors (RF) and anticardiolipin (aCL) antibodies in SLE. Using ELISA we measured serum IL-12, IL-13, RF and aCL antibodies in 73 SLE patients and 20 healthy controls. The determination of IL-12/IL-13 ratio showed that IL-12 levels were above (group A), equal to (group B) or below (group C) IL-13 levels in 71.2%, 15.1% and 13.7% of SLE patients, respectively. IgM-RF levels were significantly higher in group C than in groups A (P < 0.002) and B (P < 0.019). Group C had also higher IgM-aCL levels than group A (P < 0.04). No relationship between IL-12/IL-13 ratio and clinical or other laboratory parameters was found. It was concluded that the increased levels of both IgM-RF and IgM-aCL in patients with prevalent Th2 activity suggest that the predominance of Th2 over Th1 could drive autoantibody production in SLE patients. Received: 15 July 2002 / Accepted: 23 September 2002     

Hereditary Spastic Paraplegia Type 43 (SPG43) is Caused by Mutation in C19orf12

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three‐nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.