La Jument lighthouse: a real-scale laboratory for the study of giant waves and their loading on marine structures.

This paper presents results from an experiment designed to improve the understanding of the relationship between extreme breaking waves and their mechanical loading on heritage offshore lighthouses. The experiment, conducted at La Jument, an iconic French offshore lighthouse, featured several records of wave, current and structure accelerations acquired during severe storm conditions, with individual waves as high as 24 m. Data analysis focuses on a storm event marked by a strong peak in the horizontal accelerations measured inside La Jument. Thanks to stereo-video wave measurements synchronized to the acceleration record we were able to identify and describe the breaking wave responsible for this intense loading. Our observations suggest that this giant wave (19 m high) had a crest elevation high enough to directly hit the lighthouse tower, above the substructure. This paper reveals the potential for conducting ambitious field experiments from offshore lighthouses in order to collect valuable storm waves and wave loading observations. This offers a possible second service life for these heritage structures as in situ laboratories dedicated to the study of the coastal hydrodynamics and its interaction with marine structures. This article is part of the theme issue 'Environmental loading of heritage structures'.

Evolution of HIV-1 transmitted drug resistance in Italy in the 2007-2014 period: A weighted analysis.

BACKGROUND: Recent studies suggest that transmitted drug resistance (TDR) may be decreasing in latest years, likely because of the reduced frequency of acquired resistance. However, specific risk factors, geographical areas and special HIV-infected populations may be disproportionally affected by TDR. OBJECTIVES: Correlates of TDR and time trends were evaluated from 2007 to 2014. STUDY DESIGN: We evaluated the genotypic results of 2155 naïve patients enrolled in the I.Co.N.A cohort at 23 clinical Centers in Italy between 2007 and 2014. A weighted analysis was performed to account for the patients enrolled in the cohort in each clinical Centre at each biennium (total number of patients: 3737). RESULTS: Overall prevalence of TDR was 10.7%. Independent predictors of TDR were sexual risk factor (OR 2.315, p = 0.020) and non-Italian geographical origin (OR 1.57, p = 0.038). The weighted prevalence of TDR was 10.5% with a stable proportion over calendar years. Generally, TDR prevalence was numerically higher, although not significantly, in clinical Centers of metropolitan areas with more than 3 millions of residents as compared to others (11.3% vs. 9.2%). The difference in TDR prevalence between these Centers decreased in more recent years. CONCLUSIONS: A stable frequency of TDR was observed during the most recent years in Italy, with opposite and converging trends in large metropolitan areas as compared to the rest of the country, suggesting a more homogeneous spread of TDR across the country in latest years. Concerns remain for sexual route of infection and non-Italian origin, reinforcing the need for specific prevention strategies prioritizing specific populations.

Discrepancies between physician's perception of depression in HIV patients and self-reported CES-D-20 assessment: the DHIVA study.

Depression in HIV/AIDS patients affects adherence and disease progression and often goes unnoticed. DHIVA is a cross-sectional epidemiologic survey, investigating the prevalence of depression in people living with HIV through use of a validated self-administered scale (CES-D-20), as well and the degree of concordance between the physician's perception and patients' reports. A total of 690 HIV-infected patients attending 24 centers across Italy were enrolled. Concordance was calculated by K statistics. Association between depression and subject characteristics were evaluated through univariate and multivariate logistic models (OR and 95%CI). The prevalence of depressive symptoms was 48.8% from patient's questionnaires and 49.5% from physicians' reports, with a low/fair concordance (K = .38, p < .001). CES-D-20 found severe depression in 22.5% of the patients vs 4% identified by physicians. 135/155 (87%) of the severely depressed patients (according to CES-D-20) were considered as non or mildly/moderately depressed by physicians. Risk of severe depression was associated with unemployment (p < .001), previous depression (p < .001), treatment failure (p = .001), and former smoking status (p = .018). Depression is frequent in HIV-infected patients in the HAART era, with significant discrepancy between physician perception and the self-reported CES-D-20 results. Screening should be mandatory in all HIV patients.

Raltegravir-based therapy in a cohort of HIV/HCV co-infected individuals.

The relationship between hepatic tolerance and hepatitis C virus (HCV) co-infection has not been extensively studied in clinical practice. We assessed the efficacy and safety of raltegravir-based therapy in an Italian cohort of HIV/HCV co-infected patients. One hundred and forty patients with HIV/HCV co-infection initiating raltegravir from SCOLTA project (Surveillance Cohort Long-Term Toxicity Antiretrovirals) were examined. Of them, 43 were women, with mean age of 45.4±6.4years; 65 (46%) had undetectable HIV-RNA<50copies/mL and 75 (54%) HIV-RNA≥50copies/mL. According to CDC classification, 49 (35%) were in stage C. Based on Fib4 score at the time of starting raltegravir, patients were classified in class I in 41 cases, class II in 68 and in class III in 31 cases. Globally, the Fib4 score slightly decreased during 24months follow-up, from 2.2 to a value of 1.8. Hepatic adverse events of any grade were observed in 67 patients, of which only 2 cases (3%) had severe liver toxicity (grade 3-4). Only one patient had to discontinue the therapy because of adverse events. According to univariate analysis, being in CDC stage C represented a risk for the development of liver toxicity, with a hazard ratio (HR) of 2.27 (95% CI 1.06-4.84, P=0.033). None of the other variables considered (age, sex, years since detection of HIV and HCV-RNA detectable, years of previous HIV therapy, concomitant therapy with PI or NRTI, CD4+ cell count, Fib4, and transaminases level at baseline) resulted statistically correlated to the outcome. In conclusion, raltegravir-based regimens can be safely used in HCV infected patients; in this study, the hepatic toxicity has been found to be more frequent in patients with an advanced HIV disease (CDC stage C), independently of HIV-RNA suppression at raltegravir initiation.

Gender differences in HIV infection: is there a problem? Analysis from the SCOLTA cohorts.

OBJECTIVES: Evaluate gender differences with regard to baseline characteristics and outcome of therapy in cohorts of the SCOLTA (surveillance cohort long-term toxicity of antiretrovirals) project. METHODS: The SCOLTA project is an active pharmacovigilance system for new antiretroviral drugs. Since 2002, patients were enrolled in nine cohorts (lopinavir, tenofovir, atazanavir, fosamprenavir, enfuvirtide, tipranavir, darunavir, raltegravir and maraviroc). RESULTS: Two thousand one hundred and fifty-four patients were included in 5 PI cohorts; 607 (28.2%) were female. Women were younger and less frequently HCV-coinfected than men. At study entry, they were less frequently in CDC stage C, but CD4+ cells/mm(3) and detectable HIV-RNA were not different by gender. Women had triglycerides alterations less frequently than men, but showed a higher proportion of low HDL-cholesterol. Women were protected from incident grade 2-4 triglycerides increase (odds ratio=0.39, 95% confidence interval 0.18-0.88; P=0.02). Mean CD4+ cell count increased in both men and women; despite a non-significantly lower initial CD4+ level, women had a better immunological recovery. Women discontinued PI treatment for adverse events and their own will more frequently. CONCLUSIONS: In these cohorts, gender distribution mirrored the Italian HIV population. Women were younger than men when they started their first ARV therapy and when they entered our cohorts. On the same treatment, they had a better immune response, though no significant difference emerged on virologic control and treatment durability. As compared to men, women appeared at lower risk of hypertriglyceridaemia. They stopped PI-based treatment of their own will more frequently than men, suggesting the need for a focused effort on adherence.

Human immunodeficiency virus-1 B and non-B subtypes with the same drug resistance pattern respond similarly to antiretroviral therapy.

We analysed the 12-week virological response to protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy in 1108 patients carrying B or non-B human immunodeficiency virus (HIV)-1 subtypes with matched resistance mutation patterns. Response rates were not significantly different for non-B and B subtypes stratified for treatment status (51.5% vs. 41.5% in naïve patients; 46.7% vs. 38.7% in experienced patients) or regimens (46.9% vs. 39.7% with PI; 56.7% vs. 40% with NNRTI). No difference in response was detected in patients harbouring B and non-B subtypes with any resistance profile. Further studies are advisable to fully test this approach on larger datasets.

Changing patterns in HIV-1 non-B clade prevalence and diversity in Italy over three decades.

BACKGROUND: HIV-1 non-B subtypes have recently entered Western Europe following immigration from other regions. The distribution of non-B clades and their association with demographic factors, over the entire course of the HIV-1 epidemic, have not been fully investigated in Italy. METHODS: We carried out a phylogenetic analysis of HIV-1 pol sequences derived from 3670 patients followed at 50 Italian clinical centres over nearly three decades. RESULTS: Overall, 417 patients (11.4%) carried non-B subtypes. The prevalence of non-B strains increased from 2.6% in 1980-1992 to 18.9% in 1993-2008 (P<0.0001) in a subset of 2479 subjects with a known year of diagnosis. A multivariate analysis on a subset of 1364 patients for whom relevant demographic data were available indicated that African ethnicity, heterosexual route of infection and year of diagnosis were independently associated with non-B HIV-1 infection (P ≤ 0.0001). All pure subtypes, except for clade K, and seven circulating recombinant forms were detected, accounting for 56.6 and 34.1% of the non-B infections, respectively. The F1 subtype was the most prevalent non-B clade among Europeans and was acquired heterosexually in half of this patient population. Unique recombinant forms accounted for 9.4% of the non-B sequences and showed a B/F1 recombination pattern in one-third of cases. CONCLUSIONS: The circulation of non-B clades has significantly increased in Italy in association with demographic changes. Spread of the F1 subtype and B/F recombinants appears to predominate, which may result in a redistribution of the relative proportions of the different strains, and this could lead to overlapping epidemics. Thus, the HIV-1 landscape in Italy may in future be distinct from that of the rest of Europe.

Extensive anal condylomatosis: prognosis in relation to viral and host factors.

OBJECTIVE: To evaluate the clinical course of extensive anal condylomatosis in relation to treatment modalities, patient comorbidity and immune function, and associated papillomavirus (HPV) sequences. METHOD: Clinical data, treatment modalities and follow-up were recorded and analysed in relation to host and viral type. Histology, immunohistochemistry and molecular analyses for HPV search and typing were performed on formalin-fixed paraffin-embedded samples. RESULTS: Sixteen patients [14 males, median age 41.8 years (range 19-66)] affected by extensive anal condylomatosis [10 Buschke-Lowenstein Tumors (BLT) and 6 condylomatosis] treated in three different Italian institutions were included. There was associated preoperative anal intraepithelial neoplasia grade 3 (AIN3) in one and invasive carcinoma in three patients. After radical resection (n = 16) recurrence occurred in 4/10 (40%) BLT patients. Malignancy before or after treatment developed in 5/16 (31.25%) patients. HPV sequences were present in all the samples of 15 evaluable patients (types 6 or 11, 9 patients; type 16, 6 patients). A statistically significant association was found between presence of HPV type 16 and both malignancy and recurrence. Viral variant L83V was present in 3/4 HPV 16 positive recurrent cases. CONCLUSION: Radical resection resulted in a favourable clinical course. Typing of HPV sequences in the management of patients affected by extensive anal condylomatosis may be useful.

Laparoscopic management of incisional hernias > or = 15 cm in diameter.

BACKGROUND: Despite good results in terms of safety and minimal recurrence ensured by laparoscopy in the management of incisional hernias, the use of minimally invasive techniques for large incisional wall defects is still controversial. METHODS: Between 2002 and 2008 as many as 36 patients with abdominal wall defects > or = 15 cm were managed laparoscopically in our institution. The wall defects were > or = 20 cm in eight cases. The diameter of parietal defects was measured from within the peritoneal cavity. None had loss of domain. Body mass index (BMI) for 18 patients was > or = 30 kg/m(2). RESULTS: The mean duration of operations was 195 +/- 28 min (range 75-540). One patient needed conversion for ileal injury and massive adhesions. Post-operative complications occurred in nine patients; there were six surgical complications. Morbidity in obese and non-obese patients was not statistically different (p > 0.05). There was no postoperative death. Mean hospital stay was 4.97 +/- 3.4 days (range 2-18). Mean follow up was 28 months (range 2-68) and only one hernia recurrence was observed. CONCLUSIONS: Minimum-access procedures can provide good results in the repair of giant incisional hernia. Obesity is not a contraindication to laparoscopic repair. Further studies are expected to confirm our promising results.

Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance.

BACKGROUND: Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively. OBJECTIVES: To evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis. METHODS: The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed. RESULTS: Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%). Hyperamylasemia was more likely (17%) where a microorganism could be identified in the stools (p < 0.01). Among patients with positive stool samples, Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 %) and 10/45 (22.2%), respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P < 0.01), dehydration (18% vs 8.5%; O.R. 2.5; P < 0.05), and a higher mean number of evacuations per day (9.2 vs 7.5; P < 0.05) than those with amylasemia in the normal range. Hyperamylasemia was significantly associated with cholelithiasis, (30.0 % vs 10.7%, O.R. 3.5; P < 0.01) and chronic gastritis or duodenal ulceration (22.0 % vs 10.2%, O.R. 2.4, P < 0.05). CONCLUSIONS: Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.

Genital human papillomavirus types in immunocompetent and immunodepressed women in northeast Italy: prevalence and cytomorphological correlations.

OBJECTIVE: We evaluated the prevalence of genital human papillomavirus (HPV) types in correlation with cytomorphological findings in patients at different risk for cervical intraepithelial neoplasia living in northeast Italy. METHODS: Exfoliated cervicovaginal cells from 943 women, who were divided into three groups, were analyzed by polymerase chain reaction. RESULTS: Overall, HPV prevalence rates were 7%, 38%, and 52%, respectively. The single most frequent type was HPV 16 (18%), followed by types 6, 31, 53, 58, 61, and novel/unidentified (5-7%); other types had a frequency <5%. Infection with multiple types was present in 12%. In HIV-infected women, HPV infection was correlated with lower CD4 level and higher viral load; HGSILs were correlated only with a lower CD4 count, and no correlations were found for LGSILs. CONCLUSIONS: HGSILs were associated with high-risk types, mainly HPV 16 (40%). LGSILs, instead, were associated with a broad spectrum of low-risk and high-risk types.

The effectiveness of desensitization versus rechallenge treatment in HIV-positive patients with previous hypersensitivity to TMP-SMX: a randomized multicentric study. C.I.S.A.I. Group.

Our study was undertaken to evaluate if desensitization treatment is more effective than rechallenge in preventing hypersensitivity reactions in HIV-positive patients with previous allergic reactions to TMP-SMX; the secondary aim was to evaluate the frequency of reactions to TMP alone. This was a randomized, multicentre open study. Patients with previous documented hypersensitivity to TMP-SMX who required primary or secondary PCP prophylaxis were enrolled; subjects who had previously had serious adverse reactions to TMP-SMX were excluded. All eligible patients assumed 200 mg TMP for 14 days and in case of no reactions were randomized for desensitization or rechallenge with TMP-SMX. The patients were then followed up by periodical visits for six months. Seventy-three patients were enrolled; 14 subjects (19%) presented reactions on TMP alone during the pre-enrollment phase. The remaining 59 subjects were randomly assigned to the two treatment groups: 34 carried out desensitization (group 1) and 25 rechallenge (group 2) with TMP-SMX. Seven patients in group 1 (20.5%) and seven in group 2 (28%) showed hypersensitivity reactions during treatment; this difference was not statistically significant. No serious reaction occurred in either group. This study showed the comparable effectiveness of the desensitization procedure and rechallenge in patients with a previous, not serious, allergic reaction to TMP-SMX.

[Acute biliary pancreatitis. Therapeutic trends]. / La pancreatite biliare acuta. Nostro orientamento terapeutico.

BACKGROUND: Treatment of biliary pancreatitis includes suppression of the biliary cause by cholecystectomy and common bile duct clearance. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy for eradication of biliary stones and laparoscopic cholecystectomy (L.C.) for residual gallbladder stones would be ideal but were once considered to be contraindicated by most surgeons. The timing of definitive biliary tract surgery and the role of ERCP have been the focus of discussion in recent years. METHODS: During a two-year study period 51 patients with acute biliary pancreatitis were studied. Seven patients (14%) underwent emergency laparotomy, necrosectomy, cholecystectomy, exploration of the common bile duct and T-tube insertion, because unstable clinical conditions, with evidence of pancreatic and peripancreatic necrosis on CT-scan. Elective open cholecystectomy and CBD exploration were performed in 7 patients after the resolution of acute pancreatitis during the same hospital admission. RESULTS: Early ERCP and L.C. were associated with favourable outcomes. 33 patients underwent ERCP preoperatively: 17 within 72 hours of admission and 16 after signs of clinical improvement. Laparoscopic cholecystectomy performed 3-25 days after admission was successful in 27 of 29 patients. Postsphincterectomy bleeding occurred in one patient and was treated successfully by endoscopic epinephrine injection. For median hospital stay and recurrence there were statistical differences between early and delayed ERCP. CONCLUSIONS: ERCP and sphincterectomy have a certain role in conjunction with laparoscopic cholecystectomy in the management of patients with acute biliary pancreatitis, particularly in institutions where there is easy access to expert interventional endoscopic techniques. This policy should reduce the risk of cholangitis and recurrent pancreatitis.

Inter-rater reliability of a modified Karnofsky Scale of Performance Status for HIV-infected individuals.

The Karnofsky Scale of Performance Status (KPS) is a measure of health status that is widely used for HIV-infected persons, although few studies have documented its reliability and validity for HIV. We developed a modified KPS in an attempt to make it more appropriate for use in HIV-infected persons and evaluated its inter-rater reliability in a multicenter study. Patients (N = 657) were recruited from five hospitals in three Italian cities; responses were scored using the modified scale by three different raters in each hospital: one experienced physician, one young physician, and one nurse. Kendall's correlation test showed a strong inter-rater agreement for the total of observations: 0.82 between the two physicians, 0.77 between the experienced physician and the nurse, and 0.76 between the young physician and the nurse. The analysis of variance showed a strong effect of the stage of the disease on the KPS score. The specific hospital had little effect, whereas the effect of the type of rater disappeared when the nurse was excluded from the analysis. This modified scale demonstrated a good reliability, although training of raters could help to eliminate differences among raters and among hospitals.

Amphotericin B as primary therapy for cryptococcosis in patients with AIDS: reliability of relatively high doses administered over a relatively short period.

Thirty-one consecutive AIDS patients with cryptococcal disease were enrolled in a study of the efficacy and safety of short-course primary treatment with a relatively high dose of amphotericin B (1 mg/[kg.d] for 14 days); 26 patients also received flucytosine (100-150 mg/[kg.d], given either intravenously or orally). Twenty-five patients had cryptococcal meningitis confirmed by culture, three had presumed cryptococcal meningitis, and three had disseminated extrameningeal cryptococcosis. After successful primary treatment, all patients were given oral itraconazole or fluconazole as suppressive therapy, and their lifelong clinical and mycologic follow-up was planned. Successful primary therapy was defined as the resolution of symptoms and the documentation of negative cultures of cerebrospinal fluid and/or blood 2 months after the initial diagnosis. Therapy was successful in 29 (93.5%) of all 31 cases and in 26 (92.8%) of the 28 cases of culture-proven or presumed cryptococcal meningitis. Nephrotoxicity developed as a result of amphotericin B administration in seven cases; this adverse reaction required a reduction of the dose in two cases and the discontinuation of therapy in five. No deaths due to cryptococcosis were documented during primary therapy. Treatment failed in two cases. During a mean observation period of 10.7 months, three relapses of the underlying infection occurred. Our results indicate that an aggressive approach to the primary treatment of cryptococcosis in AIDS patients, with the administration of a relatively high dose of amphotericin B for a relatively short period, is effective and well tolerated.

[Congenital hip dysplasia. The controversial results of a screening program]. / Displasia congenita dell'anca. Risultati controversi di un programma di screening.

The authors report their experience in a screening program for congenital hip dislocation. Goal of this study is to recognize the best technique for early diagnosis in this disease. The result show that we need further study and complete cooperation between pediatrician, radiologist and orthopedist to realize the best cost/benefit ratio.

Ambroxol in the treatment of idiopathic respiratory distress syndrome. An interim report on a controlled double-blind multicenter study versus placebo.

In a double-blind multicenter study versus placebo, the therapeutic effects of ambroxol (10 mg/kg, i.v. twice daily for 7 days) were studied in an appropriately selected population with severe respiratory failure. Treatment was given to 28 neonates with birth weight less than or equal to 2,000 g, appropriate for gestational age with idiopathic respiratory distress of such severity as to require assisted ventilation (IMV or IPPV) within 12 h of birth. The preliminary results showed that ambroxol treatment, and not placebo, increased survival, reduced the time during which mechanical ventilation was required and improved the FiO2/PaO2 ratio and the biochemical indices of pulmonary maturity. This latter improvement suggests that the amelioration of the IRDS clinical picture and the reduction of ventilatory requirement might be due to an increase in pulmonary surfactant. No side effects attributable to ambroxol therapy were observed in the treated infants.