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Klippel-Trenaunay syndrome (KTS) is an uncommon congenital condition, resulting in vascular malformations affecting capillary, venous, and lymphatic systems and bone and/or soft tissue hypertrophy. Magnetic Resonance Angiography (MRA) may be useful in assessing the severity of the disease and for treatment planning. We present two cases of two white men with the typical clinical presentation of Klippel-Trenaunay syndrome i.e. vascular malformations (capillary, venous and lymphatic) and localized bone and/or soft tissues hypertrophy. Splenic hemangiomas were evidenced in both patients and MRA was helpful in assessing and delineating the abnormal venous drainage system. KTS is a complex disorder whose true prevalence and etiology are still unknown. In most cases the emblematic clinical manifestation consisting in vascular malformations and extremity overgrowth is represented. KTS may be associated with several different conditions including scoliosis and splenic hemangiomas. The presence of the lateral marginal vein (LMV) is pathognomonic. Imaging is fundamental in confirming the diagnosis and for therapeutic strategies. An effective treatment does not exist to date and a multidisciplinary approach is usually required to prevent complications.

Magnetic resonance imaging (MRI) plays a leading role in the non-invasive evaluation of bone marrow (BM). Normal BM pattern depends on the ratio and distribution of yellow and red marrow, which are subject to changes with age, pathologies, and treatments. Neonates show almost entirely red marrow. Over time, yellow marrow conversion takes place with a characteristic sequence leading to a red marrow persistence in proximal metaphyses of long bones. In adults, normal BM is composed of both red (40% water, 40% fat) and yellow marrow (15% water, 80% fat). Due to the higher content of fat, yellow marrow normally appears hyperintense on T1-weighted (T1w) fast spin echo (FSE) sequences and hypo-/iso-intense in short tau inversion recovery (STIR) T2-weighted (T2w); red marrow appears slightly hyperintense in T1w FSE and hyper-/iso-intense in STIR T2w. Pathologic BM has reduced fat and increased water percentages, resulting hypointense in T1w FSE and hyperintense in STIR T2w. In oncologic patients, BM MRI signal largely depends on the treatment (irradiation and/or chemotherapy) and its timing. BM fat and water amount and location in normal red/yellow and pathologic marrow are responsible for different signals in MRI sequences whose knowledge by radiologists may help to differentiate between normal and pathologic findings. Our aim was to discuss and illustrate the MRI of BM physiologic conversion and pathologic reconversion occurring in malignancies and after treatments in cancer patients.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Background Infections caused by multidrug-resistant Enterobacteriaceae are hard to treat and life-threatening due to reduced therapeutic options. Systemic infections caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae strains have increased in many European regions, becoming frequent in many clinical settings, and are associated with high mortality. The co-formulation of ceftazidime, a third-generation cephalosporin, with avibactam, a new suicide inhibitor beta-lactamase inhibitor able to block most Klebsiella pneumoniae carbapenemases, has been recently licensed, with promising results in patients with limited or absent therapeutic options. Little is known, however, as to the efficacy of such a combination in patients with soft tissue infections caused by multidrug-resistant Klebsiella pneumoniae carbapenemase-producing strains of Klebsiella pneumoniae. Case presentation A Caucasian 53-year-old man with paraplegia suffered multiple vertebral fractures due to a car crash. He was treated with external fixators that became infected early after insertion and were repeatedly and inefficiently treated with multiple antibiotics. He suffered repeated septic episodes caused by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae strains with a multidrug-resistant profile. Meropenem, tigecycline, and colistin combinations allowed only temporary improvements, but septic shock episodes recurred, in spite of removal of infected external fixators. After approval of pre-marketing prescription by our local Ethics Committee, full clinical resolution was obtained with a compassionate treatment using meropenem and ceftazidime/avibactam in combination for 16 days. Conclusions Our experience provides additional evidence that ceftazidime/avibactam, possibly in combination with meropenem rescued by avibactam, may be an efficacious treatment option also for complicated skin and soft tissue infections caused by multidrug-resistant strains of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae.

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.

Trichoderma species are saprophytic filamentous fungi producing localized and invasive infections that are cause of morbidity and mortality, especially in immunocompromised patients, causing up to 53 % mortality. Non-immunocompromised patients, undergoing continuous ambulatory peritoneal dialysis, are other targets of this fungus. Current molecular diagnostic tools, based on the barcode marker ITS, fail to discriminate these fungi at the species level, further increasing the difficulty associated with these infections and their generally poor prognosis. We report on the first case of endocarditis infection caused by Trichoderma longibrachiatum in a 30-year-old man. This patient underwent the implantation of an implantable cardioverter defibrillator in 2006, replaced in 2012. Two years later, the patient developed fever, treated successfully with amoxicillin followed by ciprofloxacin, but an echocardiogram showed large vegetation onto the ventricular lead. After CIED extraction, the patient had high-grade fever. The culturing of the catheter tip was positive only in samples deriving from sonication according to the 2014 ESCMID guidelines, whereas the simple washing failed to remove the biofilm cells from the plastic surface. Subsequent molecular (ITS sequencing) and microbiological (macromorphology) analyses showed that the vegetation was due to T. longibrachiatum. This report showed that T. longibrachiatum is an effective threat and that sonication is necessary for the culturing of vegetations from plastic surfaces. Limitations of the current barcode marker ITS, and the long procedures required by a multistep approach, call for the development of rapid monophasic tests.

The aim of this article is to retrospectively evaluate the patient characteristics and the most common infectious diseases in immigrant patients hospitalized in 46 Italian infectious disease clinics during 2002. The main Italian infectious disease clinics were invited to fill in a questionnaire that regarded the number and type of hospital admissions, the country of origin, and demographic features (age, sex, and resident state) of immigrants. A total of 46 clinics including 2255 patients participated in the study. Most patients were men (63%) with an age between 16 and 40 years (63.4%) covered by the National Health Service (71%) and coming from Africa (44.3%). The main infectious diseases observed were: 378 (16.76%) cases of HIV infection, 303 (13.43%) cases of tuberculosis diseases, 282 (12.5%) cases of various forms of viral hepatitis, 177 (7.84%) cases of respiratory diseases, and 196 (8.69%) gastrointestinal diseases. Tropical diseases found were 134 (5.94%) including 95 cases of malaria (70.9%). In conclusion, a broad range of diseases was noted in immigrants which were directly correlated with conditions of poverty. Only a few tropical diseases were diagnosed and therefore the immigrant should not be considered as an infectious disease carrier.

We performed a retrospective analysis of our experience with dual nucleoside regimens to look for predictors of long term benefit. We evaluated a cohort of 68 HIV-infected patients treated at 3 Italian hospital-based facilities. The results were analysed using univariate and multivariate statistical analyses. Fourty-three males and 25 females were treated for 22 ± 14 months. Sixty three patients (92.6%) suffered no or low-grade side-effects. Thirty-four patients (50 %) reached a viral load 150/μl pre-treatment viremia 1,500/μl, and no previous exposure to NRTI. Total lymphocyte counts and CD4+ T-cells showed a significant correlation. Dual NRTI regimens may be still considered for patients unable to tolerate HAART regimens and presenting with favourable predictors of response.

Extensively drug resistant Pseudomonas aeruginosa (XDR-PA) strains with limited or absent residual antimicrobial susceptibility cause a growing burden of difficult-to treat infections. Treatment options are even more limited for patients with central nervous system (CNS) involvement, as colistin-based regimens are hampered by poor blood brain barrier penetration, being often associated with insufficient clinical and microbiological success. New treatment options are awaited, but evidence from prospective evidence-based evaluations is still lacking. Here we report a case of breakthrough otogenous meningitis caused by XDR-PA in a young patient treated with meropenem and colistin for XDR-PA bloodstream infection and pneumonia after a car-crash polytrauma. The patient was treated with off-label, high-dose ceftolozane-tazobactam and high-dose fosfomycin after characterization of CNS XDR-PA isolates, with rapid clinical and microbiological resolution of meningitis. Our experience, although based on a single case, lands preliminary support to the concept that rescue regimens including ceftolozane-tazobactam and fosfomycin may be considered for XDR-PA CNS infections in patients without alternative therapeutic options. Keywords: Ceftolozane-tazobactam, Fosfomycin, XDR, Pseudomonas aeruginosa, Meningitis, Rescue therapy

We investigated the prevalence and intensity of symptoms and the use of drugs for symptom control among all HIV-infected patients reporting to the outpatient clinics or wards of 15 clinical centres in central Italy, recording clinical and epidemiological data on three consecutive days. A total of 1128 patients were observed and tabulated. Their most frequent symptoms were asthenia (55%), anorexia (34%), cough (32%), pain (29%), and fever (29%). Opioid analgesics were used in 3% of these patients and non-opioid analgesics in 13%. A large majority of HIV-infected patients presented with symptoms regardless of the stage of their disease. Pain was present in fewer than one third of patients but nonetheless seemed to be undertreated. Pain was more frequent and more intense among intravenous drug users. Based on our study, a greater effort to control symptoms in HIV patients seems to be warranted.

Introduction: HIV-infected patients have a higher risk of developing cancer than the general population. Kaposi’s sarcoma (KS), non-Hodgkin’s lymphoma (NHL), primary CNS lymphoma (PCL) and invasive cervical cancers are considered AIDS-defining. An increased incidence in recent years, however, has been reported also for other malignancies after the introduction of HAART. Methods: We performed a case-control study to characterize all HIV-infected patients with both AIDS and non-AIDS-defining neoplasms observed among all consecutive patients followed at the Infectious Diseases Unit of Pescara General Hospital, since 1991 through 2012. All cases were matched with equinumerous controls without neoplasia homogeneous for age, sex and AIDS diagnosis. Results: Out of 626 patients consecutively assisted since 1991, 57 cases of malignancy (9.1%) were observed. Of these, 45 (79.0%) occurred in males; mean age was 43.6±9.3 years; 49 (86.0%) patients were diagnosed with AIDS. Tumors observed were: NHL, 17 (29.8%); SK, 13 (22.8%); HCC, 5 (8.8%); CPL, 6 (10.5%); Hodgkin’s lymphoma, 4 (7.0%); solid tumors, 12 (21.1%), including 1 AIDS-defining tumor (anal cancer). Among these, 37 (66.1%) patients died; of them 14 (37.8%) had non-AIDS cancers. Cases were well matched with the 55 controls for sex (p=0.9), age (p=0.6) and AIDS diagnosis (p=0.6). In comparison with controls, CD4 nadirs were not different (153±151 in controls vs 136±154 cells/mmc), while CD4 at tumor diagnosis were very different between controls (463±283 cells/mmc) and cases (226±209 cells/mmc, p

Almost 1/3 of HIV-infected individuals enter health care late in the course of infection, worsening their prognosis and costs of care. According to the recent European consensus definitions, late presenters are persons presenting with CD4 counts

Intestinal adenomas are benign neoplasms that present a risk of malignancy associated with three independent characteristics: the polyp size, the histological architecture and the severity of epithelial dysplasia (or atypia). Current evidence suggests that mast cells (CM) contribute to the tumorigenesis of colorectal carcinomas. Objective: Compare the concentration of CM in intestinal adenomas and risk criteria for malignancy in these tumors (size, histological type and degree of cellular atypia). METHODS: We conducted a retrospective study with 102 anatomopathological reports of intestinal adenoma excision. We selected paraffin blocks with the central area of the tumor. The CM were stained with toluidine blue. RESULTS: In most cases (89.2%, n=91), the mast cells concentration (MC) was less than 6 CM/10 high power field (HPF) (p=0.0001). Most adenomas, regardless of their histological type, showed 0 CM/10 HPF (p=0.083). In most adenomas, regardless of their size, MC was 0 CM/10 HPF (p=0.665). Presence or absence of atypia was associated, in most cases, with MC of 0 CM/10 HPF (p=0.524). Conclusion: This study did not show association between the MC and histological type, size or presence of atypical cells in intestinal adenomas.Adenomas intestinais são neoplasias benignas que apresentam risco de malignização relacionado a três características independentes: o tamanho do pólipo, a arquitetura histológica e a gravidade da displasia (ou atipia) epitelial. Evidências atuais sugerem que os mastócitos contribuem para a tumorigênese do carcinoma colorretal. OBJETIVO: Analisar comparativamente a concentração de mastócitos em adenomas intestinais e os critérios de risco para malignização nesses tumores (tamanho, tipo histológico e grau de atipia celular). Métodos: Realizou-se um estudo retrospectivo, com seleção de 102 laudos anatomopatológicos de exérese de adenoma intestinal. Foram selecionados os blocos de parafina com a área central da neoplasia para a realização da coloração de azul de toluidina para evidenciar os mastócitos. RESULTADOS: Na maioria dos casos (89,2%, n=91) a concentração de mastócitos (CM) foi menor que 6 mastócitos/10 campos de grande aumento (CGA) (p=0,0001). A maioria dos adenomas, independente do tipo histológico, mostrou 0 mastócito/10 CGA (p=0,083). A maioria dos adenomas, independentemente do tamanho, tinha CM de 0 mastócito/10 CGA (p=0,665). A presença ou a ausência de atipias esteve associada, na maioria dos casos, a CM de 0 mastócito/10 CGA (p=0,524). CONCLUSÃO: Este estudo não mostrou associação entre a concentração de mastócitos e tipo histológico, tamanho ou presença de atipias celulares nos adenomas intestinais.

Daptomycin is licensed in adults for the management of Staphylococcus aureus methicillin-resistant infections, including bone and skin complicated infections. We describe for the first time its use in a renal transplant recipient for Fabry-Anderson Disease with right heel osteomyelitis. The patient was unresponsive to first-line Teicoplanin and second-line Tigecycline, whereas he was successfully treated with third-line Daptomycin monotherapy at 4 mg/Kg/qd for 4 weeks. Local debridement was performed in advance of each line of treatment.

Background Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors. Methods Patients diagnosed with HZ were consecutively enrolled by a network of Italian General Practitioners and Hospital Units in the health district of Pescara, Italy, over two years. Uncertain cases were referred for microbiological investigation. Data were collected through electronic case report form (e-CRFs) at enrolment and at 1, 3, 6 and 12 months after enrolment. Pain intensity was coded on a five-degree semi-quantitative scale at each time point. PHN was defined as pain of any intensity during follow-up and quantified using an area-under-the-curve (AUC) method. Results Four hundred and forty-one patients composed the final sample. Mean age was 58.1 years (SD = 20.4 years); 43.5% of patients were males; 7.9% did not receive prescription of antivirals. Intense/very intense pain at presentation was reported by 25.2% of patients and was significantly associated with female gender, older age, cigarette smoking, trauma and/or surgery at HZ site (logistic regression). PHN was diagnosed in 51.2% of patients at one month and in 30.0% of patients at three months. PHN was significantly associated with pain intensity at presentation, age, smoking, trauma and missed antiviral prescription (generalized estimating equations model). The same factors were also independent predictors of the overall pain burden as described by the AUC method (linear regression). Conclusions Smoking, traumas and surgery at the HZ site emerged as new predictors of both HZ-related pain intensity and persistence, opening new perspectives in the prevention of HZ-related pain. An independent line of evidence was provided for the efficacy of antiviral therapy in preventing PHN and reducing total pain burden.

A high level of adherence to highly active antiretroviral therapy (HAART) is essential to minimize the risk of treatment failure and HIV disease progression. This cohort study evaluated the prevalence and predictors of long-term adherence with first-line HAART in a hospital-based unselected sample of HIV patients from central Italy, and examined the association between adherence and virological response or relapse. Between July 1996 and June 2004, 171 patients (67.3% males; mean age, 41.2 years) were followed for at least 24 weeks and up to 8 years. Adherence was measured by patient self-reports and confirmed using pharmacy records. The prevalence of high-level adherence (or=90%) at 6 months was 88.3%; slightly less than 80% at 12 months. The incidence of adherence failure in the sample remained fairly stable until 24 months of follow-up, then it declined about 5% every 6 months. Cox analysis showed that compared to single/separated patients, homeless and married persons were, respectively, 1.95 times more likely and two times less likely to experience adherence failure (p0.05). The adjusted risk of adherence failure among patients who did not suffer drug-related toxicity was 0.57 (p0.05). Medication adherence was significantly associated with shorter time to virological response and longer time to relapse. Adherents were 1.69 times more likely to achieve viral suppression and nine times less likely to experience relapse than nonadherents (p0.01). Efforts at improving adherence should be prolonged for at least 24 months. A protective role of marriage for adherence failure is promising but requires confirmation in further research, that should also clarify the exact mechanisms determining the association.

Background: Data on the potential efficacy of acupuncture (AC) in controlling intense or very intense pain in patients with Herpes Zoster (HZ) has not been so far adequately assessed in comparison with standard pharmacological treatment (ST) by a controlled trial design. Methods: Within the VZV Pescara study, pain was assessed in HZ patients on a Visual Analogue Scale (VAS) and by the McGill Pain Questionnaire (MPQ) both at the beginning and at the end of treatment. Response rates, mean changes in pain intensity, differences in total pain burden with an area-under-the-curve (AUC) method over a 1-year follow-up and differences in the incidence of Post-Herpetic Neuralgia (PHN) were evaluated. Results: One hundred and two patients were randomized to receive either AC (n = 52) or ST (n = 50) for 4 weeks. Groups were comparable regarding age, sex, pain intensity at presentation and missed antiviral prescription. Both interventions were largely effective. No significant differences were observed in response rates (81.6% vs 89.2%, p = 0.8), mean reduction of VAS (4.1 +/- 2.3 vs 4.9 +/- 1.9, p = 0.12) and MPQ scores (1.3 +/- 0.9 vs 1.3 +/- 0.9, p = 0.9), incidence of PHN after 3 months (48.4% vs 46.8%, p = 0.5), and mean AUC during follow-up (199 +/136 vs 173 +/- 141, p = 0.4). No serious treatment-related adverse event was observed in both groups.

Histologic characteristics of the placentas in four cases of amnion nodosum and congenital ichthyosis, a rare association, are presented. Two cases were missed abortions of a single multiparous woman, supporting the hypothesis that in congenital ichthyosis amnion and skin share an abnormal genetic trait. As the amnion showed no hyperkeratosis, it is likely that the amniotic lesions are related to an increased deposition of keratotic plugs on the amnion. Oligohydramnios was verified in two cases; urinary tract malformations were absent in all. The histologic characteristics of the placentas were similar. Noteworthy was the aspect of the chorionic vessels, whose lumens were reduced or obliterated. Perhaps this feature contributed to the poor nutrition of the amnion, a fact assumed by some authors to explain lesions of amnion nodosum. As these vascular alterations are common after fetal death, it is only in the placenta of the newborn that the vascular changes, compatible with rubella vasculitis, may have altered the nutrition of the amnion.