Drugs for treating infections caused by non-tubercular mycobacteria: a narrative review from the study group on mycobacteria of the Italian Society of Infectious Diseases and Tropical Medicine.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients' involvement in the decision process. METHODS AND RESULTS: This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases CONCLUSIONS: Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients' care and the needs for future studies in the field of anti-NTM treatments.

Gapped Collective Charge Excitations and Interlayer Hopping in Cuprate Superconductors.

We use resonant inelastic x-ray scattering to probe the propagation of plasmons in the electron-doped cuprate superconductor Sr_{0.9}La_{0.1}CuO_{2}. We detect a plasmon gap of ∼120 meV at the two-dimensional Brillouin zone center, indicating that low-energy plasmons in Sr_{0.9}La_{0.1}CuO_{2} are not strictly acoustic. The plasmon dispersion, including the gap, is accurately captured by layered t-J-V model calculations. A similar analysis performed on recent resonant inelastic x-ray scattering data from other cuprates suggests that the plasmon gap is generic and its size is related to the magnitude of the interlayer hopping t_{z}. Our work signifies the three dimensionality of the charge dynamics in layered cuprates and provides a new method to determine t_{z}.

The music-related quality of life: Italian validation of MuRQoL into MUSQUAV questionnaire and preliminary data from a cohort of postlingually deafened cochlear implant users.

PURPOSE: Cochlear implant (CI) users do not receive much of the auditory information necessary for an accurate perception of music. This usually entails a dissatisfaction with the music they hear, so that their quality of life may potentially be affected. The main aim of this paper was to translate and validate into Italian an instrument to evaluate these aspects-The Music-Related Quality of Life Questionnaire (MuRQoL)-to help the work of clinicians and therapists. METHODS: The translation of the MuRQoL into "Questionario Musica e Qualità della Vita" (MUSQUAV) was done according to the international guidelines. The translated questionnaire was administered to normal hearing (NH) and CI users adults. Exploratory factor analysis, confirmatory factor analysis and known group method were used to confirm construct validity and applicability of MUSQUAV. RESULTS: We retrieved 225 results. The MUSQUAV questionnaire was acceptable according to the goodness-of-fit indices. The correlation between the items, evaluated using Cronbach's α coefficient, indicates a good internal consistency (> 0.80). The non-parametric Mann-Whitney test showed significant differences in the distinct populations tested. CONCLUSIONS: The MUSQUAV questionnaire is a valid, low-cost and rapid instrument for professional workers in the audiological field, especially useful in the assessment of the patients' perception and musical engagement.

Clinical characterization of gingival type of burning mouth syndrome: a cross-sectional study.

BACKGROUND: The aim of this study is to investigate the prevalence of localized intraoral neuropathic pain in a cluster of patients who reported the involvement of gingival site as only clinical manifestation of dysesthesia, analysing type and distribution of symptoms. MATERIAL AND METHODS: Burning mouth syndrome (BMS) patients were enrolled in the study. Patients were screened through laboratory test and a conventional oral examination with periodontal chart. A questionnaire to collect data on symptoms, oral site involved, quality of sleep, anxiety was submitted to all the patients. RESULTS: A total of 236 patients were recruited. Seventy-six patients (32.2%) presented generalized type, whereas 160 (67.8%) had localized type. In the localized BMS group, the gingiva was involved in 70 patients and in 33 of these it was the only site involved. In the gingival subgroup, 35 patients reported burning, 29 pain and 24 xerostomia. CONCLUSIONS: To best our knowledge, this study is the first that analyses gingival involvement as the only site in BMS and it could encourage further investigations to understand the etiopathogenesis of gingival BMS.

Correction to: Occult HBV infection in the oncohematological setting.

The original version of this article unfortunately contained a mistake.

In vivo evidence that the cannabinoid receptor 2-63 RR variant is associated with the acquisition and/or expansion of HIV infection.

OBJECTIVES: The aim of the study was to investigate whether the rs35761398 variants of the cannabinoid receptor 2 (CB2) gene may influence the acquisition of HIV infection and the clinical presentation of HIV/hepatitis C virus (HCV) coinfection. METHODS: We compared 166 HIV/HCV-coinfected patients with 186 HCV-monoinfected patients, all with biopsy-proven chronic hepatitis (using the Ishak scoring system), naïve for anti-HCV treatment and tested for the CB2 rs35761398 polymorphism (using the TaqMan assay). RESULTS: The HIV/HCV-coinfected patients were more frequently male (P < 0.002), were younger (P < 0.001), and had lower median BMI (P < 0.001) and HCV RNA (P < 0.05) and higher median aspartate aminotransferase (AST; P < 0.001), alanine aminotransferase (ALT; P < 0.001) and gamma glutamyl transferase (GGT; P < 0.001) levels than the HCV-monoinfected patients. The CB2 RR variant predominated in HIV/HCV-coinfected patients (45.8% vs. 31.2% in HCV-monoinfected patients; P < 0.001) and the CB2 QR variant in HCV-monoinfected patients (57.5% vs. 38.6% in HIV/HCV-coinfected patients; P < 0.00001), and the CB2 QQ variant was equally distributed. Focusing on patients with the CB2 QQ variant, the 26 HIV/HCV-coinfected patients, compared with the 21 HCV-monoinfected patients, showed less severe liver necroinflammation [lower histological activity index (HAI)] (P < 0.05). Of the patients with the CB2 RR variant, the 76 HIV/HCV-coinfected patients, compared with the 58 HCV-monoinfected patients, were more frequently male (P < 0.05), were younger (P < 0.001), and had a lower median body mass index (BMI; P < 0.001), a higher median AST level (P < 0.001), a higher mean HAI score (P < 0.05) and a higher rate of cases with severe steatosis (P = 0.05). In an analysis of variance (anova) of HCV/HIV-coinfected and HCV-monoinfected patient data, those with the CB2 RR variant (P = 0.003) and of male sex (P = 0.002) were more prevalent in the HCV/HIV-coinfected group. CONCLUSIONS: There is the suggestion of a positive effect of the CB2 RR variant on HIV acquisition and/or spread, which is in accordance with previous in vitro observations.

Effect of hepatitis B virus on steatosis in hepatitis C virus co-infected subjects: A multi-centre study and systematic review.

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi-centre cohort of HBV-HCV subjects, and by performing a systematic review and meta-analysis of the literature. We centrally and blindly assessed steatosis prevalence and severity in a cohort of HBV-HCV coinfected subjects compared to HCV and HBV monoinfected controls and we performed a systematic review of studies addressing the prevalence of steatosis in HBV-HCV subjects compared to HCV controls. In the clinical cohort, we included 85 HBV-HCV, 69 HBV and 112 HCV subjects from 16 international centres. There was no significant difference in steatosis prevalence between the HBV-HCV and the HCV groups (33% vs 45%, P = .11). In subgroup analysis, lean HBV-HCV subjects with detectable HBV DNA had less steatosis than lean HCV subjects matched for HCV viremia (15% vs 45%, P = .02). Our literature search identified 5 additional studies included in a systematic review. Overall, prevalence of steatosis > 5% was similar in HBV-HCV infection compared to HCV (pooled odds ratio [OR] 0.91, 95% CI 0.53-1.6) although there was significant heterogeneity (I2 69%, P = .007). In conclusion, although the prevalence of steatosis is similar in HBV-HCV compared to HCV subjects, our analysis suggests that there may be an inhibitory effect of HCV-induced steatogenesis by HBV in certain subgroups of patients.

Eighteen-month lamivudine prophylaxis on preventing occult hepatitis B virus infection reactivation in patients with haematological malignancies receiving immunosuppression therapy.

This study evaluated the long-term efficacy and safety of an 18-month lamivudine prophylaxis in 68 HBsAg-negative/anti-HBc-positive patients with oncohaematological disease. All 68 consecutive HBsAg-negative/anti-HBc-positive patients with an oncohaematological disease and naïve for chemotherapy observed from April 2008 to December 2012 at 2 Hematology Units in Naples were treated with lamivudine for 18 months after stopping chemotherapy and monitored for HBsAg at months 1 and 3 during chemotherapy and then every 3 months after its discontinuation. During follow-up, 13 (19.1%) of the 68 patients died of complications related to their oncohaematological disease, and 3 (4%) showed a virological HBV reactivation (retroconversion to HBsAg positivity) 1-7 months after the discontinuation of lamivudine prophylaxis (2 treated for chronic lymphocytic leukaemia and one for Waldenstrom's disease); of these, 2 showed a biochemical reactivation. Comparing the demographic and clinical characteristics of the 3 patients with a virological HBV reactivation to the 65 without, the former were older (median age and range: 67 years [75-78] vs. 61 [24-88]; P = .05) and were less frequently treated for B-cell non-Hodgkin lymphoma (B-NHL) (0 vs. 70.7%, P = .03). In conclusion, a 18 months of lamivudine prophylaxis was effective in preventing HBV reactivation in HBsAg-negative/anti-HBc-positive patients treated for B-NHL. However, in patients with chronic and severe immunodepression, such as those with chronic lymphocytic leukaemia and Waldenstrom's disease, prophylaxis should be continued for an indefinite period.

Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight.

The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology to climate science, yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate; visible light scattering provides insufficient resolution; and X-ray synchrotron studies have been limited to ensembles of particles. Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins, vibrational energy transfer by the hydrodynamic interaction of amino acids, and large-scale production of nanoscale structures by flame synthesis.

Role of interleukin 28-B in the spontaneous and treatment-related clearance of HCV infection in patients with chronic HBV/HCV dual infection.

The purpose of this investigation was to evaluate the role of IL28-B polymorphism in the clearance of hepatitis C virus (HCV) in chronic hepatitis B virus (HBV)/HCV coinfection during a long-term follow-up. Thirty-four consecutive patients with HBV surface antigen (HBsAg)-positive/anti-HCV-positive chronic hepatitis were retrospectively enrolled at their first liver biopsy (LB). For all patients, a documented clinical, serological and virological follow-up of at least 3 years (range 3-16 years) after LB and a sample of whole blood for genetic evaluation were available. Of the 24 patients with detectable serum HBV-DNA and HCV-RNA at their first observation, three cleared both HBV-DNA and HCV-RNA, 12 HCV-RNA and five HBV-DNA. Of the seven HBV DNA-positive/HCV RNA-negative patients at enrolment, three cleared HBV-DNA and one remained HBV DNA-positive and became HCV RNA-positive. All three HBV DNA-negative/HCV RNA-positive patients remained unchanged. Compared with the 12 patients with HCV persistence, the 15 patients who cleared HCV were younger, had lower serum alanine aminotransferase (ALT), HCV load, and histological activity index (HAI) and fibrosis score, more frequently had IL28-B CC variant, had been receiving an interferon-based treatment and less frequently cleared serum HBV-DNA. To investigate the relationship between the IL28-B variants and clearance of HCV, excluding the confounding effect of interferon-based treatment, the Mantel-Haenszel test was used, which indicated an association between HCV clearance and IL28-B variants (p = 0.009). In chronic HBV/HCV coinfection, a long-term follow-up showed a frequent spontaneous or treatment-related clearance of active replication of one or both viruses and identified the IL28-B CC genotype as an independent predictor of HCV clearance.

Acute hepatitis C: clinical and laboratory diagnosis, course of the disease, treatment.

INTRODUCTION: Acute hepatitis C (AHC) is asymptomatic in about 70-80 % of cases and, therefore, is usually undiagnosed. Although the clinical course is typically mild, AHC has a high rate of transition to chronicity. MATERIAL AND METHODS: We evaluated the literature data concerning risk factors for HCV transmission, diagnosis, natural history, and antiviral treatment of AHC. RESULTS: Although new methods have been developed, anti-HCV seroconversion remains the gold standard for the diagnosis of AHC. This phenomenon, however, is identifiable in less than half of cases in the everyday clinical practice, since most AHC patients do not know their previous anti-HCV/HCV-RNA status. An early short-term interferon treatment in AHC patients prevents progression to chronicity in most of treated patients. CONCLUSION: The literature data give evidence of the clinical relevance of an early diagnosis of AHC for an early short-term interferon treatment. There is also the suggestion to use newly developed laboratory methods to distinguish AHC from an acute exacerbation of a chronic HCV infection.

Recommendations for the management of acute hepatitis B: position paper of the Italian Society for the Study of Infectious and Tropical Diseases (SIMIT).

PURPOSE: To develop recommendations for the management of acute hepatitis B by the Italian Society for the Study of Infectious and Tropical Diseases. METHODS: Development of the recommendations divided into three levels of evidence according to the GRADE system: A (high), B (medium) and C (low experts opinion), together with three recommendation levels: 1 (strong), 2 (medium), 3 (weak). RESULTS: The treatment with antivirals is in selected cases the mainstay of management of severe acute hepatitis, and should be started as a matter of urgency in order to prevent death. CONCLUSIONS: These recommendations are meant to provide the rationale and practical indications for the management of acute hepatitis B (AHB).

Application and internal validation of lung ultrasound score in COVID-19 setting: The ECOVITA observational study.

BACKGROUND: The severe acute respiratory syndrome Coronarovirus-2 associated still causes a significant number of deaths and hospitalizations mainly by the development of respiratory failure. We aim to validate lung ultrasound score in order to predict mortality and the severity of the clinical course related to the need of respiratory support. METHODS: In this prospective multicenter hospital-based cohort study, all adult patients with diagnosis of SARS-CoV-2 infection, performed by real-time reverse transcription polymerase chain reaction were included. Upon admission, all patients underwent blood gas analysis and lung ultrasound by expert operators. The acquisition of ultrasound scan was performed on 12 peculiar anatomic landmarks of the chest. Lung ultrasound findings were classified according to a scoring method, ranging 0 to 3: Score 0: normal A-lines. Score 1: multiple separated B-lines. Score 2: coalescent B-lines, alteration of pleural line. Score 3: consolidation area. RESULTS: One thousand and seven patients were included in statistical analysis (male 62.4 %, mean age 66.3). Oxygen support was needed in 811 (80.5 %) patients. The median ultrasound score was 24 and the risk of having more invasive respiratory support increased in relation to higher values score computed. Lung ultrasound score showed negative strong correlation (rho: -0.71) with the P/F ratio and a significant association with in-hospital mortality (OR 1.11, 95 %CI 1.07-1.14; p < 0.001), even after adjustment with the following variables (age, sex, P/F ratio, SpO2, lactate, hypertension, chronic renal failure, diabetes, and obesity). CONCLUSIONS: The novelty of this research corroborates and validates the 12-field lung ultrasound score as tool for predicting mortality and severity clinical course in COVID-19 patients. Baseline lung ultrasound score was associated with in-hospital mortality and requirement of intensive respiratory support and predict the risk of IOT among COVID-19 patients.

Abdominal fat interacts with PNPLA3 I148M, but not with the APOC3 variant in the pathogenesis of liver steatosis in chronic hepatitis C.

The patatin-like phospholipase domain-containing 3 gene (PNPLA3) and the apolipoprotein C3 gene (APOC3) have been studied in relation to liver steatosis and liver disease outcome. The aim of this study was to evaluate the influence of PNPLA3 p.I148M and APOC3 rs2854116 and rs2854117 polymorphisms on the clinical and histological presentation of chronic hepatitis C in an Italian population and their relationship with viral and anthropometric parameters. Patients with hepatitis C (n = 166) entered the study receiving a clinical, histological, virological and biochemical evaluation. APOC3 (rs2854116 and rs2854117) and PNPLA3 (p.I148M) variants were genotyped. PNPLA3 polymorphisms were associated with liver steatosis, which was significantly higher in patients with p.148I/M (P = 0.034) and p.148M/M (P = 0.004) variants than those homozygous for the PNPLA3 wild type. Excluding patients with HCV genotype 3, the association with liver steatosis and PNPLA3 variants was more marked (p.148I/I genotype vs p.148I/M, P = 0.02, and vs p.148M/M, P = 0.005). The APOC3 polymorphism was not associated with any of the evaluated parameters. Among the interacting factors, BMI and waist circumference correlated with liver steatosis (P = 0.008 and 0.004, respectively). Relationship between waist circumference and liver steatosis was analysed for the different PNPLA3 genotypes. Homozygous 148M patients showed a stronger correlation between waist circumference and steatosis than those carrying the other genotypes (P = 0.0047). In our hepatitis C-infected population, the PNPLA3 polymorphism influenced the development of liver steatosis, but not fibrosis progression. APOC3 polymorphisms had no effect on the development of steatosis and no influence on the PNPLA3 polymorphism. The amount of abdominal fat can increase the association of PNPLA3 p.I148M with liver steatosis.

Factors influencing liver fibrosis and necroinflammation in HIV/HCV coinfection and HCV monoinfection.

OBJECTIVES: To define differences in liver histology between HIV/HCV coinfection and HCV monoinfection, and to investigate possible causative factors. METHODS: Liver biopsies (LBs) from 440 consecutive HIV/HCV-coinfected patients (Group HIV/HCV) and 374 consecutive HCV-monoinfected patients (Group HCV) were evaluated for necroinflammation and fibrosis (Ishak) by a pathologist unaware of the clinical and laboratory data. All patients were HBsAg-negative, with no history of alcohol abuse and naïve to anti-HCV treatment. At LB, 78.4% of patients in Group HIV/HCV were on an antiretroviral regimen. RESULTS: HIV/HCV-coinfected patients compared to the HCV-monoinfected patients were younger (p < 0.0001), more frequently males (p < 0.0001), and had HCV genotype 3 (p < 0.0001); they showed a good immunological condition (CD4+ cell count: 518 ± 166 cells/mm(3)). Patients in Group HIV/HCV more frequently showed a fibrosis score ≥4 (27.5 vs. 20.6%, p < 0.05) and a necroinflammation score ≥9 (25.9 vs. 13.4%; p < 0.0001). The prevalence of patients with fibrosis score ≥4 was significantly higher in older age classes in both Group HIV/HCV (p < 0.005) and Group HCV (p < 0.05). A necroinflammation score ≥9 was significantly higher in older age classes only in Group HIV/HCV (p < 0.05). A multivariate analysis for Group HIV/HCV revealed that the patient age and nadir of CD4+ cell count were independently associated to higher degrees of fibrosis, the patient age and antiretroviral treatment were associated to higher degrees of necroinflammation, and HCV genotype 3 was associated to higher degrees of steatosis. CONCLUSION: The data suggest a need for early anti-HCV treatment in both HCV-monoinfected and HIV/HCV-coinfected patients.

Peripheral ameloblastic fibroma: a rare case report.

CASE REPORT: Ameloblastic fibroma is a rare mixed odontogenic tumour which involves mostly the posterior mandible. Its peripheral variant is very rare. Only eight cases have been reported worldwide. In this report, we described a case of peripheral ameloblastic fibroma occurring in the maxillary gingiva in a 10 year-old child. The lesion was excised with a conservative surgical approach and no recurrence has occurred. Peripheral ameloblastic fibroma should be considered in the differential diagnosis of a slow growing lesion involving the gingiva.

Tolerability and efficacy of anti-HBV nucleos(t)ide analogues in HBV-DNA-positive cirrhotic patients with HBV/HCV dual infection.

We evaluated tolerability and virological and clinical impact of anti-Hepatitis B Virus (HBV) nucleos(t)ide analogues in cirrhotic patients with HBV/Hepatitis C Virus (HCV) coinfection. The virological and clinical course of 24 consecutive HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis was compared with that of 24 HBsAg/HBV-DNA-positive, anti-HCV-negative cirrhotic patients, pair-matched for age (±5 years), sex, HBeAg/anti-HBe status and Child-Pugh class. Patients in both groups were previously untreated with oral antiviral agents at enrollment and were treated for at least 24 months (range 24-54). At the 12th and 18th month of treatment, HBV-DNA was negative in 21 (87.5%) and 23 (95.8%) patients with hepatitis B and C and in 20 (83.3%) and 22 (91.6%) in patients with isolated HBV; all patients in both groups were HBV-DNA-negative at month 24 and at subsequent observations. Treatment was well tolerated by all patients in both groups. At the last observation (for co-infected patients, median 44 months and range 24-54; for mono-infected patients, median 40 months and range 24-54), a deterioration in Child class was observed in eight (47%) of 17 patients in patients with both HBV and HCV who were HCV-RNA-positive at baseline, but in none of seven HCV-RNA-negative patients in the same group, and in one patient (4.2%) in the mono-infected patients. Reactivation of HCV infection was relatively infrequent (12.5% of cases) and never associated with a clinical deterioration. Treatment with nucleotides in HBsAg/HBV-DNA/anti-HCV-positive patients with cirrhosis showed a favourable virological effect in all cases, but a favourable clinical result only in the HCV-RNA-negative at baseline.

Femtosecond dark-field imaging with an X-ray free electron laser.

The emergence of femtosecond diffractive imaging with X-ray lasers has enabled pioneering structural studies of isolated particles, such as viruses, at nanometer length scales. However, the issue of missing low frequency data significantly limits the potential of X-ray lasers to reveal sub-nanometer details of micrometer-sized samples. We have developed a new technique of dark-field coherent diffractive imaging to simultaneously overcome the missing data issue and enable us to harness the unique contrast mechanisms available in dark-field microscopy. Images of airborne particulate matter (soot) up to two microns in length were obtained using single-shot diffraction patterns obtained at the Linac Coherent Light Source, four times the size of objects previously imaged in similar experiments. This technique opens the door to femtosecond diffractive imaging of a wide range of micrometer-sized materials that exhibit irreproducible complexity down to the nanoscale, including airborne particulate matter, small cells, bacteria and gold-labeled biological samples.

Nanoplasma dynamics of single large xenon clusters irradiated with superintense x-ray pulses from the linac coherent light source free-electron laser.

The plasma dynamics of single mesoscopic Xe particles irradiated with intense femtosecond x-ray pulses exceeding 10(16) W/cm2 from the Linac Coherent Light Source free-electron laser are investigated. Simultaneous recording of diffraction patterns and ion spectra allows eliminating the influence of the laser focal volume intensity and particle size distribution. The data show that for clusters illuminated with intense x-ray pulses, highly charged ionization fragments in a narrow distribution are created and that the nanoplasma recombination is efficiently suppressed.