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Purpose: Acinetobacter baumannii (Ab) is a Gram-negative opportunistic bacterium responsible for nosocomial infections or colonizations. It is considered one of the most alarming pathogens due to its multi-drug resistance and due to its mortality rate, ranging from 34 to 44,5% of hospitalized patients. The aim of the work is to create a predictive mortality model for hospitalized patient with Ab infection or colonization., Methods: A cohort of 140 sequentially hospitalized patients were randomized into a training cohort (TC) (100 patients) and a validation cohort (VC) (40 patients). Statistical bivariate analysis was performed to identify variables discriminating surviving patients from deceased ones in the TC, considering both admission time (T0) and infection detection time (T1) parameters. A custom logistic regression model was created and compared with models obtained from the "status" variable alone (Ab colonization/infection), SAPS II, and APACHE II scores. ROC curves were built to identify the best cut-off for each model., Results: Ab infection status, use of penicillin within 90 days prior to ward admission, acidosis, Glasgow Coma Scale, blood pressure, hemoglobin and use of NIV entered the logistic regression model. Our model was confirmed to have a better sensitivity (63%), specificity (85%) and accuracy (80%) than the other models., Conclusion: Our predictive mortality model demonstrated to be a reliable and feasible model to predict mortality in Ab infected/colonized hospitalized patients., (© 2024. The Author(s).)

Rationale: Erdheim-Chester disease (ECD) is a rare multisystemic disease characterized by the infiltration of multiple organs by foamy CD68 + CD1a-histiocytes. The genetic background consists of gain-of-function somatic mutations in the mitogen-activated protein kinase pathway. The purpose of the present paper is to make a contribution to the scientific literature on ECD by reporting our experience with a complex clinical case report, along with a concise review of the literature. We discussed the unusual clinical presentation, the complex diagnostic process and the comparison with other published cases., Patient Concerns: A 70-year-old man presented with arthralgia due to multiple bone areas of sclerosis, first diagnosed with metastases of a prostatic neoplasm. Sequential thorax-abdomen, femoral and homer contrast-enhanced computed tomography (CT) showed pericardial effusion, pulmonary fibrosis, and perirenal fibrous tissue as "hairy kidneys." He underwent. Three bone biopsies were unsuccessful to reach diagnosis., Diagnoses: A xanthelasma biopsy showed histopathological signs compatible with ECD; genetic analysis showed the mutation BRAFV600E., Interventions: The patient underwent targeted therapy with vemurafenib (BRAF-inhibitor), discontinued 2 weeks later due to the onset of a diffuse erythematous papular rash on the trunk and limbs., Outcomes: At the 1-year follow-up, there was only progression of chronic kidney disease (CKD)., Lessons: The present case report describes how ECD diagnosis could represent a challenge for clinicians, owing to its heterogeneous clinical presentation. Early diagnosis followed by prompt therapy is essential for modifying the natural history of the disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Phenylketonuria (PKU) is a metabolic disorder necessitating lifelong management to prevent severe neurological impairments. This paper synthesises clinical practices from Italian specialist centres to delineate a unified approach for administering pegvaliase, a novel enzyme replacement therapy for PKU., Methods: Virtual meetings convened in September 2022, gathering a steering committee (SC) of experts from five Italian centres specialising in PKU. The SC reviewed, and discussed clinical practices, and formulated recommendations for pegvaliase treatment., Results: The SC outlined a comprehensive treatment roadmap for PKU management with pegvaliase, emphasising the importance of multidisciplinary care teams, patient selection, pre-treatment evaluation, and education. Recommendations include initial hospital-based pegvaliase administration, regular monitoring of phenylalanine and tyrosine levels, dietary adjustments, and management of adverse events. A consensus was reached on the need for a digital database to manage treatment plans and enhance communication between healthcare professionals and patients., Conclusion: The expert panel's consensus highlights the complexity of PKU management and the necessity for a coordinated, patient-centred approach. The recommendations aim to standardise care across Italian centres and provide a framework for integrating pegvaliase therapy into clinical practice, potentially informing international guidelines. Further research is warranted to evaluate the long-term impact of these practices on patient outcomes and quality of life., Competing Interests: None., (© 2024 Published by Elsevier Inc.)

Background: Alcohol binge drinking may compromise the functioning of the nucleus accumbens (NAc), i.e. the neural hub for processing reward and aversive responses., Methods: As socially stressful events pose particular challenges at developmental stages, this research applied the resident-intruder paradigm as a model of social stress, to highlight behavioural neuroendocrine and molecular maladaptive plasticity in rats at withdrawal from binge-like alcohol exposure in adolescence. In search of a rescue agent, cannabidiol (CBD) was selected due to its favourable effects on alcohol- and stress-related harms., Results: Binge-like alcohol exposed intruder rats displayed a compromised defensive behaviour against the resident and a blunted response of the stress system, in addition to indexes of abnormal dopamine (DA)/glutamate plasticity and dysfunctional spine dynamics in the NAc. CBD administration (60 mg/kg) was able to: (1) increase social exploration in the binge-like alcohol exposed intruder rats, at the expenses of freezing time, and in control rats, which received less aggressive attacks from the resident; (2) reduce corticosterone levels independently on alcohol previous exposure; (3) restore DA transmission and (4) facilitate excitatory postsynaptic strength and remodelling., Conclusions: Overall, the maladaptive behavioural and synaptic plasticity promoted by the intersection between binge-like alcohol withdrawal and exposure to adverse social stress can be rescued by a CBD détente effect that results in a successful defensive strategy, supported by a functional endocrine and synaptic plasticity. The current data highlight CBD's relevant therapeutic potential in alcohol- and stress-related harms, and prompt further investigation on its molecular targets.

Statin-induced autoimmune myositis (SIAM) represents a rare clinical entity that can be triggered by prolonged statin treatment. Its pathogenetic substrate consists of an autoimmune-mediated mechanism, evidenced by the detection of antibodies directed against the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR Ab), the target enzyme of statin therapies. To facilitate the diagnosis of nuanced SIAM clinical cases, the present study proposes an "experience-based" diagnostic algorithm for SIAM. We have analyzed the clinical data of 69 patients diagnosed with SIAM. Sixty-seven patients have been collected from the 55 available and complete case records regarding SIAM in the literature; the other 2 patients represent our direct clinical experience and their case records have been detailed. From the analysis of the clinical features of 69 patients, we have constructed the diagnostic algorithm, which starts from the recognition of suggestive symptoms of SIAM. Further steps provide for CK values dosage, musculoskeletal MR, EMG/ENG of upper-lower limbs and, Anti-HMGCR Ab testing and, where possible, the muscle biopsy. A global evaluation of the collected clinical features may suggest a more severe disease in female patients. Atorvastatin proved to be the most used hypolipidemic therapy., (© 2023. The Author(s).)

Klinefelter's syndrome (KS) is the main cause of hypogonadism and infertility in men and is often related to obesity, metabolic syndrome, and diabetes. The purpose of our real-life observational study was to investigate the metabolic and anthropometric parameters in a population of patients with Klinefelter syndrome compared to a group of healthy age-matched subjects. Methods . In our study, 25 consecutive Caucasian adult outpatients (age range 21-52 years, mean age 32.9 ± 12.2) with KS in testosterone replacement therapy and 30 healthy men (age range 25-45 years, mean age 32.4 ± 7.62) were studied. In both groups of subjects, anthropometric indices, lipid profile, glucose metabolic parameters, HbA1c, the homeostasis model assessment estimate of HOMA-insulin resistance (IR), and the insulin sensitivity index (ISI) were evaluated. In addition, we assessed the complete hormonal gonadic status and irisin values in both groups of patients. Results . No significant differences were found in BMI and total blood testosterone levels between KS and control subjects. Patients with KS had significantly higher values of WC ( p =0.028), HbA1c ( p =0.018), HOMA-IR ( p < 0.001), FSH ( p < 0.001), LH ( p < 0.001), estradiol ( p =0.001), and irisin ( p =0.029) and significantly lower HDL-cholesterol ( p =0.002), AMH ( p < 0.001), inhibin B ( p < 0.001), and ISI-Matsuda ( p < 0.001) compared to healthy controls. Univariate analysis revealed an inverse correlation between irisin and ISI-Matsuda (r = -0.128; p =0.010). These data were then confirmed in multivariate analysis. Conclusions . KS is characterized by early development of metabolic syndrome and in particular by alterations of the glucose metabolism, independently of testosterone levels serum and BMI. Irisin blood levels of Klinefelter's patients are higher than in healthy subjects and positively correlate with the degree of insulin resistance., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Stefano Radellini et al.)

Aim: In this study, our aim was to assess the prevalence of sedentariness and overweight/obesity, two modifiable risk factors for non-communicable diseases (NCDs), and to investigate the geographic variability in their association with socio-economic status (SES) and family characteristics in Italian adults., Methods: The Multipurpose Survey on Health Conditions and the Recourse to Health Services (MSHC), 2012/2013 edition, conducted by the National Institute of Statistics was used as data source. The sample for this study included 99,479 interviewed people aged 18 and over, which are representative of about 50 million persons. For the scope of this analysis, data were considered as individuals nested within families within regions and analysed through multilevel models., Results: It was estimated that 39.8% of Italian adults are sedentary, 38.1% are partially active and 22.1% are physically active; 11.3% of Italian adults are obese and the 34.5% are overweight. There was evidence of inverse socio-economic gradient for both sedentariness and body mass index (BMI). There was higher risk of sedentariness for one-parent (odds ratio (OR) = 1.10; 95% confidence interval (CI) = (1.02; 1.20)) and other family types (OR = 1.34; 95% CI = (1.20; 1.48 )) compared with couples with children. Also, the relative variation of BMI was statistically significant for one-parent, one-person and other families ( p < 0.05). An increasing north-south gradient was suggested for BMI, but not for sedentariness., Conclusions: Policy interventions could be addressed to reduce BMI levels in the southern area and to encourage physical activity in regions with high sedentariness. The Italian family is the key driver to promote virtuous healthy behaviours.

The present study aimed to evaluate the characteristics and quality of statistical methodology used in clinical studies on dentin hypersensitivity management. An electronic search was performed for data published from 2009 to 2014 by using PubMed, Ovid/MEDLINE, and Cochrane Library databases. The primary search terms were used in combination. Eligibility criteria included randomized clinical trials that evaluated the efficacy of desensitizing agents in terms of reducing dentin hypersensitivity. A total of 40 studies were considered eligible for assessment of quality statistical methodology. The four main concerns identified were i) use of nonparametric tests in the presence of large samples, coupled with lack of information about normality and equality of variances of the response; ii) lack of P-value adjustment for multiple comparisons; iii) failure to account for interactions between treatment and follow-up time; and iv) no information about the number of teeth examined per patient and the consequent lack of cluster-specific approach in data analysis. Owing to these concerns, statistical methodology was judged as inappropriate in 77.1% of the 35 studies that used parametric methods. Additional studies with appropriate statistical analysis are required to obtain appropriate assessment of the efficacy of desensitizing agents.

Unlabelled: We isolated, identified and characterized yeast strains from grapes, and their fermented musts, sampled in the small island of Linosa, where there are no wineries and therefore the possibility of territory contamination by industrial strains is minimal. By traditional culture-dependent methods, we isolated 3805 colonies, distinguished by molecular methods in 17 different species. Five hundred and forty-four isolates were analysed for the main oenological characteristics such as fermentative vigour with and without sulphites, sugar consumption and production of alcohol, volatile acidity, hydrogen sulphide, glycerol and β-glucosidase. This analysis identified Kluyveromyces marxianus (seldomly used in winemaking) as the most interesting candidate yeast for the production of innovative wines., Significance and Impact of the Study: In recent years, interest is growing for wine production by non-Saccharomyces yeasts, both in research and in the industry. This study describes the yeast population of the grapes in a small-secluded island in the Mediterranean Sea, useful site for the search of new strains. Evaluation of fundamental oenological characters identifies potential best yeasts to assay in experimental vinifications. We also describe, for the first time, 14 new colony morphologies on WL Nutrient Agar, culture medium used to monitor the yeast population dynamics., (© 2016 The Society for Applied Microbiology.)

Incidence data on pertussis cases in Italy do not show pertussis resurgence as recently described in other European countries. The aim of this study was to determine the seroprevalence of IgG antibodies to pertussis toxin (PT-IgG) in selected adult age groups, who can serve as a reservoir of Bordetella pertussis and be responsible for onward transmission to vulnerable infants. The seroprevalence of PT-IgG was studied in sera collected in 2012-2013 in three age groups: 20-29 years and 30-39 years (reproductive age), and ≥60 years. These data were compared to those from sera collected in similar age groups in 1996-1997. More than 80 % of the adult population analysed in the 2012-2013 group presented detectable levels of PT-IgG (>5 IU ml -1 ). PT-IgG titres of 50-99 IU ml -1 , considered indicative of infection in the last few years, and PT-IgG titres of  ≥100 IU ml -1 , considered indicative of recent infection (i.e.within the last year), reached 9.1 % [95 % confidence interval (CI) 6.9-11.3‌  %; 58/639] and 5 % (95 % CI 3.3-6.7 %; 32/639) seroprevalence, respectively. Notably, the proportion of subjects with a seroprevalence indicative of recent infection increased significantly from 9.3 % (95 % CI 7.5-11.1 %; 96/1037) in 1996-1997 to 14.1 % (95 % CI 11.4-16.8 %; 90/639) in 2012-2013. Overall, our data clearly indicate a significant increase in the circulation of B. pertussis in adults in Italy; therefore, it is likely that the statutory notification system underestimates the real incidence of the disease. These findings have implications for preventive strategies.

We describe the occurrence of measles in an 18 month-old patient in Sicily, Italy, in March 2015, who received the first dose of a measles-containing vaccine seven days before onset of prodromal symptoms. Measles virus infection was confirmed by PCR and detection of specific immunoglobulin; viral genotyping permitted the confirmation of a vaccine-associated illness. The patient had a concurrent influenza virus infection, during a seasonal epidemic outbreak of influenza.

Objectives: To systematically review the evidence for a synergistic effect of combining rehabilitation with biological anti-tumour necrosis factor (TNF) therapy in patients with ankylosing spondylitis (AS)., Methods: Data were analysed to identify the most effective rehabilitation programmes, the best endpoints for effectiveness, and patient subgroups most likely to benefit from combination therapy. Systematic MEDLINE and Embase searches were performed to identify studies evaluating rehabilitation programmes and biological therapy in patients with AS. Evidence was categorised by study type, and efficacy, adverse effects and other outcomes were summarised., Results: Of the 75 studies identified, 13 investigated the combination of a rehabilitation programme with TNF inhibitor therapy, while the remainder studied rehabilitation with standard therapy (often not specified). Data from these few studies suggest that combined rehabilitation plus anti-TNF therapy is more effective in terms of symptom severity, disease activity, disability and quality-of-life indices versus biologic alone or rehabilitation with standard medical therapy, or, in non-comparative studies, compared with baseline. The most effective rehabilitation appears to be supervised or in-patient programmes with an educational component. Available data do not provide guidance on most appropriate endpoints or identify patients most likely to benefit from combination therapy. Combined, TNF inhibitor and rehabilitation therapy appear to have a synergistic effect, possibly due to increased adherence to exercise. Exercise regimes are more effective if supervised and include an education component., Conclusions: Further randomized, controlled trials comparing endpoints and investigating longer-term benefits of combining TNF inhibitors with rehabilitation in different AS subgroups are needed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: We examined the molecular epidemiology of Acinetobacter baumannii clinical isolates from two cities (Tehran and Tabriz) of Iran., Methods: DiversiLab repetitive extragenic palindromic PCR (rep-PCR), multilocus sequence typing and sequence group multiplex PCR were performed. The presence of resistance mechanisms including metallo-β-lactamases, extended-spectrum β-lactamases, OXA carbapenemases, aminoglycoside-modifying enzymes and RNA methylases was also investigated., Results: DiversiLab rep-PCR identified 11 clusters and 11 singleton isolates. Twelve sequence types (STs), including six novel types, were identified. Sequence groups (SGs) 1-3 as well as five additional banding patterns were detected by multiplex PCR. A local outbreak in a general hospital in Tabriz with an SG1/ST2 profile was identified. Isolates of international clone II showed the highest prevalence and the most heterogeneous combination of resistance determinants., Conclusions: Several different multiresistant strains of A. baumannii were shown to circulate in Iran. The selection and spread of the SG1/ST2 clone might have been favoured by the acquisition of resistance genes in the absence of adequate infection control measures., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Mechanisms associated with reactivation of hepatitis B virus (HBV) in patients with occult HBV infection (OBI) remain unclear. In some cases immunosuppression is an enhancer of viral replication. However, not all patients with OBI who undergo immunosuppression experience reactivation. This study explores the role of viral heterogeneity as a determinant of occult HBV reactivation. HBV genotype, mutation patterns and quasispecies were assessed by sequencing the PreS/S region of 16 patients with OBI undergoing chemotherapy, 3 of whom experienced a OBI reactivation. The latter were also assessed at the time of reactivation. Phylogenetic analysis identified low nucleotide and amino acid diversity rates. There were no differences in the viral quasispecies, or common mutation patterns, detected between patients who underwent reactivation of OBI, and those who did not. Furthermore, upon reactivation, the quasispecies evolved towards a loss of most of the variants present during the initial OBI stage, probably representing the fittest version of the virus. The genetic variability of HBV alone did not account for the transition from occult to overt infection, which appears to be governed principally by the host immune response.

Recent reports indicate an increase in rates of infection and disease due to rapidly growing mycobacteria (RGM) in patients with pre-existing chronic lung disease. Studies have described difficulties in correctly identifying closely related species, even when proper methodologies are adopted, and several different gene targets have been proposed. We describe two cases of RGM infection in a 29-year-old HIV-1 positive Congolese man and a 19-year-old HIV-1 positive Liberian woman, respectively, both with bronchiectasis due to previous Mycobacterium tuberculosis (MTB) infection. Mycobacterium porcinum and Mycobacterium bolletii were identified in bronchoalveolar lavage fluid and sputum, respectively. After starting the patients on antiretroviral treatment and primary prophylaxis against non-tuberculous mycobacteria (NTM), and ensuring that they adhered to their prescribed regimen, we observed an improvement in their clinical condition and mycobacteria cleared from their respiratory specimens. Management of RGM respiratory infection in immunocompromised patients has to be evaluated on a case-by-case basis, taking into account the patient's pulmonary sequelae, adherence to multiple treatments and immune profile.

This paper describes the epidemiology of hospitalised cases with influenza-like illness (ILI) and laboratory-confirmed influenza A cases in Sicily (Italy) during the 2009 influenza pandemic. The first ILI case diagnosed as infected with pandemic influenza A(H1N1)2009 in Sicily was reported in June 2009 and it rapidly became the dominant circulating strain. In the period from 30 April 2009 through 31 December 2010, a total of 2,636 people in Sicily were hospitalised for ILI and 1,193 were laboratory-confirmed for influenza A. Basic demographic and clinical information for all hospitalised patients was collected and population mortality rates (PMRs) and case fatality ratios (CFRs) were calculated. The median age of hospitalised patients infected with pandemic influenza A(H1N1)2009 was significantly lower than that of hospitalised ILI cases in general (18.0 vs. 32.1 years; p<0.0001). Among adults, women were more susceptible than men. The majority of clinical presentations were mild, but 6.6% of hospitalised patients required admission to an intensive care unit, of whom 26.3% had confirmed influenza A. Twenty-four fatal cases were documented. The age group of 45–54 year-olds showed the highest PMRs once hospitalised, while CFRs were higher in elderly patients of 65 years and older. All fatal cases were confirmed as influenza A(H1N1)2009 and most of them had established risk factors for influenza complications.

Polymerase chain reaction (PCR-) ribotyping was performed on 243 strains of Salmonella enterica serotype Enteritidis isolated during the years 1980-1994 from 58 foodborne outbreaks occurring in different regions of Italy. The majority (37) of the outbreaks were attributed to phage type (PT) 4, followed by PT1 (seven outbreaks); the latter was identified in 1993 in Italy in epidemic strains of Enteritidis. In eight cases more than one phage type was recognised from a single event. Nine PCR-ribotypes (PCR-RTs) were detected, with a strong prevalence of PCR-RTs f7 and e5 (23 and 21 outbreaks, respectively). In two instances two distinct PCR-RTs were identified within strains from a single outbreak. All but one of the PT1 outbreaks were caused by PCR-RT f7, whereas PT4 outbreaks could be subdivided into six subsets. Clustering of isolates was consistent with data obtained from epidemiological investigations. PCR-ribotyping proved to be an effective and reliable tool for subtyping isolates of Enteritidis belonging to the most frequent phage types. Nevertheless, in terms of laboratory expertise and lack of inter-laboratory standardisation, this typing technique is best suited for reference laboratories.

Characterization of 169 strains of Salmonella typhi of phage types C1, C4, D1 and D9 isolated in 1975-88 was carried out by rDNA gene restriction pattern analysis. Twenty-four isolates had been recovered during four large waterbone outbreaks in the last 20 years in Sicily; 145 strains, isolated from apparently sporadic cases of infection in Southern Italy in the same period of time, were also examined. Application of rRNA-DNA hybridization technique after digestion of chromosomal DNA with Cla I showed the identity of patterns of the epidemic strains of phage types C1 and D1, confirming attribution of the outbreaks to single bacterial clones. Patterns of the two available strains of lysotype D9 were slightly different, whilst the 12 epidemic strains of phage type C4 could be assigned to two distinct patterns scarcely related to each other and, consequently, to two different clones. A considerable heterogeneity was detected among all apparently sporadic isolates of the four phage types under study. This fingerprinting method appears a reliable tool to complement phage typing in characterizing isolates of S. typhi. In particular, epidemiological features of spread of this salmonella serovar in areas, where simultaneous circulation of indigenous and imported strains occurs, can be elucidated.