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Giant warts are infrequent dermatological viral infections caused by Papillomavirus (HPV) in immune-compromised patients. Treatment may often be difficult and unsatisfactory, either by surgery or cytotoxic agents, because of poor immune control of viral activity in such hosts. Here we report on the case of a patient with advanced and persistent immune suppression caused by HIV disease, who developed a monstrous wart covering the entirety of the radial district of his right hand. He was completely healed after a long treatment with traditional Chinese acupuncture, in spite of minimal immune recovery induced by efficacious antiretroviral therapy. To the best of our knowledge, therefore, the present report may be the first direct clinical evidence that acupuncture may be effective in the treatment of cutaneous warts also in HIV-infected patients.

Background: Neuromyelitis optica spectrum disorders (NMOSDs) are degenerative diseases frequently associated with severe recurrences and high risk of progressive disability. In this report, we describe an unusual case of a patient with the coexistence between NMOSD and mixed connective tissue disease (MCTD)., Case Description: A 58-year-old Caucasian man was admitted to the Emergency Department (ED) with low back pain and walking inability. He had an unsteady gait, paraesthesia of the lower limbs and pain in the left lumbar area of the spine. He previously manifested repeated episodes of Raynaud's phenomenon. The neurological examination revealed pyramidal signs with asymmetric and progressive paraparesis associated with hypoesthesia and bladder dysfunction. A spine magnetic resonance imaging (MRI) revealed the presence of a long extensive cervico-dorsal myelitis. Among laboratory analyses, serum immunometric examinations came back positive for anti-RNP (272 U/mL) and anti-SSA (20 U/mL) antibodies, whereas a recombinant immunofluorescence assay revealed the presence of immunoglobulin G (IgG) antibodies against AQP4. Consequently, he was treated with high-doses of corticosteroids, with progressive resolution of symptoms. To date, his last cervico-dorsal spine MRI showed negative results., Conclusions: Only a few anecdotal cases of the coexistence between NMOSD and MCTD have so far been described, and many clinical aspects of this association are not yet fully known. Missed diagnosis of rheumatologic or neurologic diseases may lead to treatment delay and, potentially, irreversible disability. Closer collaboration between neurologists and rheumatologists is needed for the early diagnosis of both diseases., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-23-48/coif). The authors have no conflicts of interest to declare., (2025 AME Publishing Company. All rights reserved.)

Background: Dalbavancin is a long-acting lipoglycopeptide, approved for treatment of skin and skin structure infections. Its PK/PD profile and safety allow for short hospital stays even in the case of difficult-to-treat infections requiring long courses of therapy, e.g., osteomyelitis, cardiovascular, and prosthetic infections. Objectives: We aimed to evaluate the safety and efficacy of dalbavancin in real life settings for both in-label and off-label indications. Methods: retrospective evaluation of all consecutive patients treated with dalbavancin at our site between May 2017 and September 2021. Results: A total of 100 patients treated with dalbavancin and followed up for 6 months after treatment (58% male; median age 63.5 years, median Charlson Comorbidity Index CCI = 2.7, 28% inpatients) were included with the following indications: acute bacterial skin and skin structure infections (22%), bone and prosthetic infections (57%), and cardiovascular infections (19%). Infections were caused by MSSA (30%), MRSA (5%), MR-CoNS (20%), and Streptococcus spp. (8%). In 32 cases, no isolate was obtained. The average number of infusions was 5 (s.d. = 3). Neither ensuing alteration of renal function nor neutropenia or thrombocytopenia were observed during treatment and follow-up. Two self-limiting skin rashes occurred. The overall clinical success rate was 84%-91% for registered and 82% for unregistered indications. The prescription of higher loading doses was the only predictor independently associated with better outcomes in multivariate models (OR: 5.2, 95%CI: 1.5-17.9, p < 0.01). Conclusions: Dalbavancin proved to be effective for skin and skin structure infections, as well as for difficult-to-treat infections in highly comorbid patients. Regarding tolerability, our results support the use of dalbavancin for long-lasting treatments of deep-seated infections.

Background: Multidrug-resistant Acinetobacter baumannii (CRAB) infections are a serious problem in critical care. This study aims to develop an early prognostic score for immune paralysis, using practical and cost-effective parameters, to predict ICU mortality in patients with CRAB infections being treated with Cefiderocol. Methods: We carried out an observational pilot study on consecutive patients hospitalized in the ICU with ensuing septic Acinetobacter baumannii infections treated with Cefiderocol monotherapy or Cefiderocol including combinations. We investigated the predictive power of lymphocyte counts, lymphocyte subpopulations, serum cholinesterase levels, and reactivation of herpes viruses. Results: Overall, 36 of 39 patients entered in our analysis: 20 survivors and 16 deceased. A total of 12 patients developed bacteremia, 19 patients had HAP/VAP, and 5 patients had a soft tissue infection. Univariate analyses of factors associated with unfavorable outcome revealed a significant association for age (OR: 1.5, CI: 1.11-2.02), SAPS II (OR: 1.05, CI: 1.01-1.1), SOFA score (OR: 1.37, CI: 1.06-1.76), lymphocytopenia (OR: 32.5, CI: 3.45-306.4), viral reactivation (OR: 9.75, CI: 1.72-55.4), and cholinesterase drop <1600 U/L (OR: 39.7, CI: 5.8-271.6). At variance, monotherapy or associations with Cefiderocol were not associated. In the final multivariable model, the only independent predictors of death were age (OR: 1.42, CI: 0.98-2.05), lymphocytopenia (OR: 18.2, CI: 0.87-371), and cholinesterase drop to below 1600 U/L (OR: 9.7, CI: 0.77-123.7). Conclusions: Age, lymphocytopenia, and serum cholinesterase drops, which were nearly significantly associated with an unfavorable outcome, may help pinpoint patients with acute immune paralysis during sepsis. Knowledge of such an immune state may in turn directly influence patients' care.

Background: Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions., Methods: We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist., Results: The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%., Conclusions: Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background: We investigated the possible role of the immune profile at ICU admission, among other well characterized clinical and laboratory predictors of unfavorable outcome in COVID-19 patients assisted in ICU., Methods: Retrospective analysis of clinical and laboratory data collected for all consecutive patients admitted to the ICUs of the General Hospital of Pescara (Abruzzo, Italy), between 1 st March 2020 and 30 th April 2021, with a confirmed diagnosis of COVID-19 respiratory failure. Logistic regressions were used to identify independent predictors of bacteremia and mortality., Results: Out of 431 patients included in the study, bacteremia was present in N = 191 (44.3%) and death occurred in N = 210 (48.7%). After multivariate analysis, increased risk of bacteremia was found for viral reactivation (OR = 3.28; 95% CI:1.83-6.08), pronation (3.36; 2.12-5.37) and orotracheal intubation (2.51; 1.58-4.02). Increased mortality was found for bacteremia (2.05; 1.31-3.22), viral reactivation (2.29; 1.29-4.19) and lymphocytes < 0.6 × 10 3 c/µL (2.32; 1.49-3.64)., Conclusions: We found that viral reactivation, mostly due to Herpesviridae, was associated with increased risk of both bacteremia and mortality. In addition, pronation and intubation are strong predictors of bacteremia, which in turn together with severe lymphocytopenia due to SARS-CoV2 was associated with increased mortality. Most episodes of bacteremia, even due to Acinetobacter spp, were not predicted by microbiological evidence of colonization., (© 2023. The Author(s).)

Background: Undesired intrathecal injections represent an important subset of medical errors, albeit rare. Clinical effects depend on the type and concentration of drug(s) injected. Here we report on the case of a healthy woman with persistent low back pain, treated with a paravertebral injection of lidocaine, thiocolchicoside, and L-acetylcarnitine at an orthopedic practice., Case Report: A 42-year-old Caucasian woman, with no relevant past medical history, received a lumbar paravertebral injection of lidocaine, thiocolchicoside, and L-acetylcarnitine for persistent low back pain. Approximately 30 minutes after injection, she experienced quick neurological worsening. Upon arrival at the Emergency Department, she was comatose, with fixed bilateral mydriasis, trismus, and mixed acidosis; seizures ensued in the first hours; slow progressive amelioration was observed by day 6; retrograde amnesia was the only clinical relevant remaining symptom by 6 months., Conclusions: To our knowledge, this is the first reported case of inadvertent intrathecal thiocolchicoside injection in an adult patient, as well as the first in the neurosurgical literature. Our experience suggests that injection therapy for low back pain should be administered in adequate settings, where possible complications may be promptly treated., (© 2023. The Author(s).)

Background: Monocyte Distribution Width (MDW), a simple cellular marker of innate monocyte activation, can be used for the early recognition of sepsis. We performed an observational prospective monocentric study to assess the predictive role of MDW in detecting sepsis in a sample of consecutive patients presenting at the Emergency Department., Methods: Prospective observational study using demographic and clinical characteristics, past medical history and other laboratory measurements to predict confirmed sepsis using multivariate logistic regression., Results: A total of 2724 patients were included in the study, of which 272 (10%) had sepsis or septic shock. After adjusting for known and potential risk factors, logistic regression found the following independent predictors of sepsis: SIRS equal to 1 (OR: 2.32, 1.16-4.89) and 2 or more (OR: 27.8, 14.8-56.4), MDW > 22 (OR: 3.73, 2.46-5.70), smoking (OR: 3.0, 1.22-7.31), end stage renal function (OR: 2.3, 1.25-4.22), neurodegenerative disease (OR: 2.2, 1.31-3.68), Neutrophils ≥ 8.9 × 10 3 /µL (OR: 2.73, 1.82-4.11), Lymphocytes < 1.3 × 10 3 /µL (OR: 1.72, 1.17-2.53) and CRP ≥ 19.1 mg/L (OR: 2.57, 1.63-4.08). A risk score derived from predictive models achieved high accuracy by using an optimal threshold (AUC: 95%; 93-97%)., Conclusions: The study suggests that incorporating MDW in the clinical decision process may improve the early identification of sepsis, with minimal additional effort on the standard procedures adopted during emergency care., (© 2022. The Author(s).)

Background: The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn's Disease (CD) with ensuing neurological symptoms., Case Presentation: A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn's Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure., Conclusions: Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing., (© 2022. The Author(s).)

Background: The hospital management of patients diagnosed with COVID-19 can be hampered by heterogeneous characteristics at entry into the emergency department. We aimed to identify demographic, clinical and laboratory parameters associated with higher risks of hospitalisation, oxygen support, admission to intensive care and death, to build a risk score for clinical decision making at presentation to the emergency department., Methods: We carried out a retrospective study using linked administrative data and laboratory parameters available in the initial phase of the pandemic at the emergency department of the regional reference hospital of Pescara, Abruzzo, Italy, March-June 2020. Logistic regression and Cox modelling were used to identify independent predictors for risk stratification. Validation was carried out collecting data from an extended timeframe covering other variants of concern, including Alpha (December 2020-January 2021) and Delta/Omicron (January-March 2022)., Results: Several clinical and laboratory parameters were significantly associated to the outcomes of interest, independently from age and gender. The strongest predictors were: for hospitalisation, monocyte distribution width ≥ 22 (4.09; 2.21-7.72) and diabetes (OR = 3.04; 1.09-9.84); for oxygen support: saturation < 95% (OR = 11.01; 3.75-41.14), lactate dehydrogenase≥237 U/L (OR = 5.93; 2.40-15.39) and lymphocytes< 1.2 × 10 3 /μL (OR = 4.49; 1.84-11.53); for intensive care, end stage renal disease (OR = 59.42; 2.43-2230.60), lactate dehydrogenase≥334 U/L (OR = 5.59; 2.46-13.84), D-dimer≥2.37 mg/L (OR = 5.18; 1.14-26.36), monocyte distribution width ≥ 25 (OR = 3.32; 1.39-8.50); for death, procalcitonin≥0.2 ng/mL (HR = 2.86; 1.95-4.19) and saturation < 96% (HR = 2.74; 1.76-4.28). Risk scores derived from predictive models using optimal thresholds achieved values of the area under the curve between 81 and 91%. Validation of the scoring algorithm for the evolving virus achieved accuracy between 65 and 84%., Conclusions: A set of parameters that are normally available at emergency departments of any hospital can be used to stratify patients with COVID-19 at risk of severe conditions. The method shall be calibrated to support timely clinical decision during the first hours of admission with different variants of concern., (© 2022. The Author(s).)

Background: Monocyte Distribution Width (MDW), a simple proxy marker of innate monocyte activation, can be used for the early recognition of sepsis along with Procalcitonin. This study explored the added value of MDW as an early predictor of ensuing sepsis in patients hospitalised in an Intensive Care Unit., Methods: We performed an observational prospective monocentric study to estimate the analytical performance of MDW in detecting ensuing sepsis in a sample of consecutive patients assisted in an Intensive Care Unit for > 48 h for any reason. Demographic and clinical characteristics, past medical history and other laboratory measurements were included as potential predictors of confirmed sepsis in multivariate logistic regression., Results: A total of 211 patients were observed, 129 of whom were included in the final sample due to the suspect of ensuing sepsis; of these, 74 (57%) had a confirmed diagnosis of sepsis, which was best predicted with the combination of MDW > 23.0 and PCT > 0.5 ng/mL (Positive Predictive Value, PPV: 92.6, 95% CI: 82.1-97.9). The best MDW cut-off to rule out sepsis was ≤20.0 (Negative Predictive Value, NPV: 86.4, 95% CI: 65.1-97.1). Multivariate analyses using both MDW and PCT found a significant association for MDW > 23 only (OR:17.64, 95% CI: 5.53-67.91)., Conclusion: We found that values of MDW > 23 were associated with a high PPV for sepsis, whereas values of MDW ≤ 20 were associated with a high NPV. Our findings suggest that MDW may help clinicians to monitor ICU patients at risk of sepsis, with minimal additional efforts over standard of care., (© 2021. The Author(s).)

Background: Early recognition of patients hospitalized for sepsis at higher risk of poor clinical outcome is a mandatory task and many studies suggested that indicators of the immune status may be useful for this purpose. We performed a retrospective, monocentric cohort study to evaluate whether lymphocyte subsets may be useful in predicting in-hospital mortality of septic patients., Methods: Data of all consecutive patients with a diagnosis of sepsis at discharge and an available peripherical blood lymphocyte subset (CD4, CD8, CD16/CD56 and CD19) analysis at hospital entry were retrospectively collected between January 2015 and August 2018. Clinical characteristics of patients, past medical history and other laboratory parameters were also considered., Results: Two-hundred-seventy-eight septic patients, 171 (61.5%) males, mean age 63.2 ± 19.6 years, were enrolled. Total counts of lymphocytes, CD4 T cells, CD8 T cells and B cells were found significantly lower in deceased than in surviving patients. At univariate analyses, CD4 T cells/µL (OR 0.99 for each incremental unit, 95%CI 0.99-1.10, p < 0.0001), age (OR 1.06, 95%CI 1.04-1.09, p < 0.0001), procalcitonin (OR 1.01, 95%CI 1.01-1.02, p < 0.0001) and female gender (OR 2.81, 95%CI 1.49-5.28, p = 0.001) were associated with in-hospital mortality. When a dichotomic threshold of < 400/µL for CD4 T cells as a dependent variable was considered in multivariate models, age (OR 1.04; 95%CI 1.01-1.09, p = 0.018); female gender (OR 3.18; 95%CI 1.40-7.20, p = 0.006), qSOFA (OR 4.00, 95%CI 1.84-8.67, p < 0.001) and CD4 T cells < 400/µL (OR 5.3; 95%CI 1.65-17.00, p = 0.005) were the independent predictors., Conclusions: In adjunct to biomarkers routinely determined for the prediction of prognosis in sepsis, CD4 T lymphocytes, measured at hospital entry, may be useful in identifying patients at higher risk of in-hospital death., (© 2021. The Author(s).)

Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3)., Methods: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols., Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4). RAS prevalence was 15.8% in DAA-naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF-failures. In NS5A-failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA-naïve, P < .001) followed by A30K (12.7% vs 2.8% in DAA-naïve, P < .001). Analysing baseline samples, a higher prevalence of NS5A-RASs was observed before treatment in DAA-failures (5/13, 38.5%) vs DAA-naïves (61/393, 15.5%, P = .04). Regarding 228 DAA-naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A-RASs (P = .002)., Conclusions: In this real-life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A-RASs, the most frequent being Y93H. The presence of natural NS5A-RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain-1 interacts with cellular proteins inducing pro-oncogenic pathways. Thus, we explore genetic variations in NS5A domain-1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype-1b infected DAA-naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7-82.3); p < 0.001). Focusing on HCC-group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4-6.2) log IU/mL vs. 5.3 (4.4-5.6) log IU/mL, p = 0.02) and lower ALT (35 (30-71) vs. 83 (48-108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell-cycle regulation (p53, p85-PIK3, and β-catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV-mediated oncogenesis. The role of theseNS5A domain-1 mutations in triggering pro-oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation.

Aim: This study aimed to evaluate the safety and efficacy profile of low-dose tocilizumab (TCZ), to prevent disease progression, subcutaneously administered to patients with moderate COVID-19 pneumonia and hyperinflammation., Methods: Clinical characteristics and outcomes were retrospectively analysed of patients - with laboratory-confirmed bilateral COVID-19 pneumonia, hyperinflammation (C-reactive protein (CRP) ≥20 mg/dL), no hypoxaemia (oxygen saturation >90%), and no contraindications to TCZ - who were treated with subcutaneous TCZ (324 mg) administered within 48 h from hospitalization on top of standard of care (SOC). They were compared with matched controls treated with SOC only before TCZ was available at the institution. Clinical data were available for all patients until death or until day 35 for those discharged from hospital., Findings: Ten consecutive patients (six males, median age 55 years) treated with TCZ on top of SOC, and ten patients (six males, median age 56 years) treated with SOC only were included. TCZ was well-tolerated with no clinically relevant adverse events. TCZ was associated with a reduction in CRP at day 1 (-50%, IQR -28 to -80) and day 3 (-89%, IQR -79 to -96; p =  0.005 for within-group), whereas there was no significant change in CRP values in the SOC group (p <  0.001 for between-group comparisons at both time points). TCZ resulted in a parallel improvement in oxygenation, as assessed by the ratio of partial pressure of oxygen to fraction of inspired oxygen (P/F) ratio, which increased at day 1 (+11%, IQR +6 to +16; p =  0.005 for within-group and p =  0.006 for between-group comparisons), and day 3 (+23%, IQR +16 to +34; p =  0.005 for within-group and p = 0.003 for between-group comparisons). None of the TCZ-treated patients had disease progression, defined as requirement of oxygen therapy or mechanical ventilation, whereas progression occurred in five (50%) patients among the SOC group., Conclusions: Low-dose subcutaneous TCZ may be a safe and promising therapeutic option administered on top of SOC to prevent disease progression in hospitalised patients with moderate COVID-19 and hyperinflammation., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We carried out a prospective observational study to evaluate whether Monocyte Distribution Width (MDW) may play a role in identifying patients with sepsis in comparison with Procalcitonin (PCT). We prospectively enrolled all consecutive patients hospitalized at the Infectious Diseases Unit of Pescara General Hospital for bacterial infection or sepsis. MDW values were collected for all patients. Clinical characteristics, demographic data, past and present medical history, microbiological results, PCT, as well as neutrophil and monocytes indices at entry were compared in the 2 groups. Two-hundred-sixty patients were enrolled, 63.5% males, aged 59.1±19.5 years. Sepsis was diagnosed in 105 (40.4%); in 60 (57.1%) at least 1 microorganism was isolated from blood cultures. In multivariate models, MDW as a continuous variable (OR:1.57 for each unit increase; 95%CI: 1.31-1.87, p<0.001) and PCT˃1 ng/mL (OR: 48.5; 95%CI: 14.7-160.1, p<0.001) were independently associated with sepsis. Statistical best cut points associated with sepsis were 22.0 for MDW and 1.0 ng/mL for PCT whereas MDW values<20 were invariably associated with negative blood cultures. At ROC curve analysis, the AUC of MDW (0.87) was nearly overlapping that of PCT (0.88). Our data suggest that incorporating MDW within current routine WBC counts and indices may be of remarkable use for detection of sepsis. Further research is warranted., Competing Interests: The authors have declared that no competing interests exist

Background: Psychological factors (PFs) are known predictors of cardiovascular disease (CVD) in many clinical settings, but data are lacking for human immunodeficiency virus (HIV) infection. We carried out a prospective study to evaluate (1) psychological predictors of preclinical and clinical vascular disease and (2) all-cause mortality (ACM) in HIV patients., Methods: We conducted a cross-sectional analysis of baseline data to evaluate the predictors of carotid plaques (CPs) and a prospective analysis to explore predictors of vascular events (VEs) and ACM over 10 years. Human immunodeficiency virus patients monitored at the Infectious Disease Units of 6 Italian regions were consecutively enrolled. Traditional CVD risk factors, PFs (depressive symptoms, alexithymia, distress personality), and CPs were investigated. Vascular events and ACM after enrollment were censored at March 2018., Results: A multicenter cohort of 712 HIV-positive patients (75.3% males, aged 46.1 ± 10.1 years) was recruited. One hundred seventy-five (31.6%) patients had CPs at baseline. At the cross-sectional analysis, alexithymia was independently associated with CPs (odds ratio, 4.93; 95% confidence interval [CI], 2.90-8.50; P < .001), after adjustment for sociodemographic, clinical, and psychological variables. After an average follow-up of 4.4 ± 2.4 years, 54 (7.6%) patients developed a VE, whereas 41 (5.68%) died. Age, current smoking, hypertension, and alexithymia (hazard ratio [HR], 3.66; 95% CI, 1.80-7.44; P < .001) were independent predictors of VE. Likewise, alexithymia was an independent predictor of ACM (HR, 3.93; 95% CI, 1.65-9.0; P = .002), regardless of other clinical predictors., Conclusions: The present results validate our previous monocentric finding. Alexithymia may be an additional tool for the multifactorial assessment of cardiovascular risk in HIV., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Gram-negative Multi-Drug-Resistant Organisms (GNMDROs) cause an increasing burden of disease in Intensive Care Units (ICUs). We deployed a multifaceted intervention to control selection and transmission of GNMDROs and to estimate at which rate GNMDROs would decline with our interventional bundle., Methods: Interventions implemented in 2015: in-ward Antimicrobial-Stewardship-Program for appropriate management of antimicrobial prescription; infection monitoring with nasal/rectal swabs and repeated procalcitonin assays; 24 h microbiological support (since 2016); prevention of catheter-related infections, VAPs and in-ward GNMDROs transmission; education of ICU personnel. In May 2017, epidemiological, clinical and microbiological data were collected and retrospectively analyzed. Rates of resistance in Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, as well as percentages of resistance among all Gram-negative bacteria were compared during the study period., Results: Of 668 patients, at least one isolate was obtained from 399 patients. The proportions of patients with infection and with Gram-negative isolates were even across the 5 semesters (p = 0.8). For Klebsiella pneumoniae, the number of strains resistant to carbapenems fell from 94% to 6% (p < 0.001). Significant drops were also observed for Pseudomonas aeruginosa and Acinetobacter baumannii. Percentages of resistance for all Gram-negative isolates fell from 91% to 13% (p < 0.0001). The reduction in antibiotic prescription translated in a considerable reduction of pharmacy costs. Multivariate models confirmed that the hospitalization semester was the most relevant independent predictor of resistance among Gram-negative bacteria., Conclusions: Our experience provides further evidence that a multi-faceted intervention, aimed to reduce selection and transmission of GNMDROs with efficient microbiological support, may yield remarkable results in a short time interval., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Prevention and control of hospital and community acquired infections caused by multi drug resistant organisms (MDROs) are one major priority nowadays for health care systems worldwide. To improve actions and plans to tackle this problem, the creation of automated regional, national and international MDRO surveillance networks is a mandatory path for international health Institutions and Ministries. In this paper, the authors report on the surveillance system designed for the Abruzzo Region (Central Italy) to monitor the prevalence of MDROs in both infected and colonized patients, to verify appropriateness of antibiotic prescription in hospitalized patients and to interact with other national and sovra-national networks. Service Oriented Architecture (SOA) approach, different Healthcare Service Specification Project (HSSP) standards, local, national and international terminology and Clinical Document Architecture Release 2 (CDA R2) were adopted to design the overall architecture of this regional surveillance system. The Authors discuss the state of implementation of the project, itemizing specific design and implementation choices adopted so far and sketching next steps and reasons of some design and implementation choices, and indicate the next steps.

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016., Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list., Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169-521 cells/μL], and the median viral load was 4.7 log 10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log 10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log 10 higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02)., Conclusions: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy., (© 2018 British HIV Association.)

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.

Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2-45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4-19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1-4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.

Objective: This study aimed to analyze the efficacy of a Web-based testing programme in terms of the prevention of late HIV presentation. The clinical characteristics of patients diagnosed with HIV via the Web-based testing programme were compared to those of patients diagnosed in parallel via standard diagnostic care procedures., Methods: This study included the clinical and demographic data of newly diagnosed HIV patients enrolled at the study clinic between February 2014 and June 2017. These patients were diagnosed either via standard diagnostic procedures or as a result of the Web-based testing programme., Results: Eighty-eight new cases of HIV were consecutively enrolled; their mean age was 39.1±13.0 years. Fifty-nine patients (67%) were diagnosed through standard diagnostic procedures and 29 (33%) patients came from the Web-based testing programme. Late presentation (62% vs. 34%, p=0.01) and AIDS-defining conditions at presentation (13 vs. 1, p=0.02) were significantly more frequent in the standard care group than in the Web-based group; four of 13 patients with AIDS diagnosed under standard diagnostic procedures died, versus none in the Web-based testing group (p<0.001)., Conclusions: Web-based recruitment for voluntary and free HIV testing helped to diagnose patients with less advanced HIV disease and no risk of death, from all at-risk groups, in comparison with standard care testing., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A better knowledge of factors predicting the development of sepsis in patients hospitalized in intensive care unit (ICU) might help deploy more targeted preventive and therapeutic strategies. In addition to the known clinical and demographic predictors of septic syndromes, in this study, we investigated whether measuring T and B lymphocyte subsets upon admission in the ICU may help individualize the prediction of ensuing sepsis during ICU stay. Between May 2015 and December 2016, we performed a prospective cohort study evaluating peripheral blood lymphocyte T-CD4+ (T-helper cells), T-CD8+ (cytotoxic T-cells), T-CD56 + (natural killer cells), and T-CD19+ (B-lymphocytes), using flow cytometry on blood samples collected 2 days after admission in the ICU. We enrolled 176 patients, 65.3% males, with mean age of 61.1 ± 15.4 years. At univariate analyses, higher percentages of CD19 B-cells were significantly associated with ensuing sepsis (20.5% (15.7-27.7)% vs 16.9% (11.3-22)%, P = 0.0001), whereas median interquartile range (IQR) proportions of CD4 T-cells (41.2% (33.4-50.6)% vs 40% (35-47)%, P = 0.5), CD8 T-cells (21.1% (15.8-28.2)% vs 19.6% (14.6-25.1)%, P = 0.2) and CD56 T-cells (1.7% (0.9-3.1)% vs 1.45% (0.7-2.3)%, P = 0.4) did not reveal any significant association. An unexpected, highly significant inverse correlation of CD8 T-cells and CD19 B-cells proportions, however, was observed, suggesting that patients with lower CD19 and higher CD8 proportions might be somehow protected from ensuing sepsis. We therefore studied the ability of the CD8/CD19 ratio to predict ensuing sepsis in our sample. In final models of multivariate logistic regression, the following independent associations were found: previous antibiotic exposure (odds ratio (OR): 3.8 (95% confidence interval (CI): 1.35-10.87), P = 0.01), isolation of at least one multi-drug resistant organism at any time during ICU stay (OR: 8.4 (95% CI: 3.47-20.6), P < 0.0001), decreasing age (OR: 0.9 (95% CI: 0.93-0.99), P = 0.02) and a CD8/CD19 ratio >2.2 (OR: 10.3 (95% CI: 1.91-55.36), P = 0.007). Our data provide preliminary evidence that immune characterization of critically ill patients on ICU admission may help personalize the prediction of ensuing sepsis during their ICU stay. Further polycentric evaluation of the true potential of this new tool is warranted.

Background: Pretreatment evaluation of HCV-infected patients is a complex interplay between multiple clinical and viral parameters, leading to a tailored approach that may bring real-life sustained virological response (SVR) rates close to 98%-99%., Objectives: As proof-of-concept, we evaluated the efficacy of all-oral direct-acting antiviral (DAA) regimens in patients whose personalization included pre-therapy evaluation of natural resistance-associated substitutions (RASs), in addition to international guideline recommendations., Methods: One hundred and thirty-one patients who started a first-line all-oral DAA regimen between April 2015 and December 2016 were tested for baseline NS3 and NS5A RASs by Sanger sequencing. SVR12 was defined as HCV-RNA undetectability 12 weeks after treatment discontinuation., Results: Compatibly with a real-life context, 74.0% (97 of 131) of patients presented ≥2 pretreatment risk factors for failure to achieve SVR12 (infection by GT-1a/GT-3a; cirrhosis; previous treatment experience; HCV-RNA ≥800 000 IU/mL) and 33.6% had ≥3 risk factors. Natural RASs were frequently detected (32.1% prevalence), with substantial prevalence of NS5A RASs (15.3%), mostly represented by Y93H in GT-1b (3 of 36, 8.3%) and GT-3a (3 of 25, 12.0%) and F28C in GT-2c (2 of 11, 18.2%). Overall, personalized treatment led to 100% SVR12, even in those patients for whom treatment strategy was either strengthened (by ribavirin inclusion and/or duration increase) or simplified (by ribavirin exclusion and/or duration reduction), thanks to baseline RAS evaluation., Conclusions: Even with newer DAA regimens, an integrated interpretation of clinical and virological pretreatment parameters, including natural RASs, may play a relevant role in bringing SVR rates close to the highest achievable. Treatment tailoring can be foreseen in 'hard-to-treat' patients, but also in 'easy' patients with favourable indicators, whereby a simplification/shortening of recommended regimens can be indicated., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR., Study Design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization., Results: HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p<0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted δ and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted λ, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p<0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR., Conclusions: Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis.

Background: In critically ill patients with colonization/infection of multidrug-resistant organisms, source control surgery is one of the major determinants of clinical success. In more complex cases, the use of different tools for sepsis management may allow survival until complete source control., Case Presentation: A 42-year-old white man presented with traumatic hemorrhagic shock. Unstable pelvic fractures led to emergency stabilization surgery. Fever ensued with diarrhea, followed by septic shock. Two weeks later, an abdominal computed tomography scan revealed suprapubic and ischiatic abscesses at surgical sites, as well as dilated bowel. Debridement of both surgical sites, performed with vacuum-assisted closure therapy, yielded isolates of carbapenem and colistin-resistant Klebsiella pneumoniae. Antibiotic treatment was de-escalated after 21 days; 4 days later fever, leukocytosis, hypotension and acute renal failure relapsed. Blood purification techniques were started, for the removal of endotoxin and inflammatory mediators, with sequential hemodialysis. Clinical improvement ensued; blood cultures yielded Candida albicans and multidrug-resistant Acinetobacter baumannii; panresistant carbapenemase-producing Klebsiella pneumoniae grew from wound swabs. In spite of shock reversal, our patient remained febrile, with diarrhea. Control blood cultures yielded Candida albicans, Acinetobacter baumannii and carbapenem-resistant Klebsiella pneumoniae. His abdominal pain increased, paralleled by a right flank palpable mass. Colonoscopy revealed patchy serpiginous ulcers. At exploratory laparotomy, an inflammatory post-traumatic pseudotumor of his right colon was removed. Blood cultures turned negative after surgery. Septic shock, however, relapsed 4 days later. A blood purification cycle was repeated and combination antimicrobial therapy continued. Surgical wounds and blood cultures were persistently positive for carbapenem-resistant Klebsiella pneumoniae. Removal of pelvic synthesis media was therefore anticipated. Three weeks later, clinical, microbiological, and biochemical evidence of infection resolved., Conclusions: High quality intensive assistance for sepsis episodes needs a clear plan of cure, aimed to complete infection source control, in a complex multidisciplinary interplay of specialists and intensive care physicians.

Background: Substantial evidence indicates that perinatal mental disturbances are associated with the risk for negative maternal-newborn outcomes. A neuroendocrine brain-placenta interaction has been described to explain the association between prenatal stress-related disorders and placental abnormalities. Whether these mechanisms may affect the likelihood of mother-to-child transmission (MTCT) of infections has never been investigated., Aims: To evaluate the role of psychological factors in cytomegalovirus (CMV) MTCT in pregnant women with primary CMV infection., Method: A cohort of 276 pregnant women with primary CMV infection underwent assessment of (a) reactive psychopathological symptoms, such as current depressive symptoms and ongoing symptoms of post-traumatic stress disorder; and (b) stable personality traits, such as alexithymia and Type D (distressed) personality. Congenital infection was diagnosed by CMV DNA amplification from blood and/or urine and saliva from newborn at birth., Results: The occurrence of congenital CMV disease in the newborn was independently predicted by post-traumatic stress symptoms during pregnancy., Conclusions: Our findings suggest that psychological stress-related disturbances may weaken the physical and immunological barrier against the mother-to-fetus transmission of viruses., Declaration of Interest: We declare that we have no conflicting interests to disclose., Copyright and Usage: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Undiagnosed cases of HIV infection in developed countries are estimated at 20-30% of individuals living with HIV. Web-based strategies may represent a new approach to easier, wider, and unrestricted access to early testing. The Abruzzo Region, Italy, developed a Web-based tool to recruit persons at high risk of HIV and other sexually transmitted infections (STIs). At the Website www.failtestanchetu.it , browsers found information on STIs (HIV, hepatitis B and C, and syphilis), a structured questionnaire called "risk calculator" to assess one's own risk behaviors and direct booking of their test at one of six sites throughout the region. The Website was advertised on local media and in pharmacies, high schools, sports facilities, and factories. Between February 1, 2014, and May 31, 2015, about 6000 users visited the Website; 3046 people attended a visit for counseling on risk behaviors, signs, or symptoms of STIs and accepted blood drawing for HIV, hepatitis B Virus (HBV), hepatitis C Virus (HCV), and syphilis tests. Fifty-eight (1.90%) subjects were positive for HCV, 56 (1.84%) for HBsAg, 90 (2.95%) for Treponema pallidum antibodies, and 28 (0.92%) for HIV. Ninety-two percent of HIV-positive patients were successfully linked to care. Late presenters were less frequent in this sample than in the population diagnosed with HIV in Italy in 2014. An overall 7% proportion of HIV, HBV, HCV, and syphilis-unaware cases were all transferred to care, with the exception of three people. HIV seropositivity among testers was higher than 2/1000, the cost-effectiveness threshold suggested for effective testing. Therefore, our Web-based unrestricted and free access methodology appears worth further and wider evaluation.

Available commercial assays may yield inaccurate hepatitis C virus (HCV) genotype assignment in up to 10% of cases. We investigated the cost-effectiveness of re-evaluating HCV genotype by population sequencing, prior to choosing a direct acting antiviral (DAA) regimen. Between March and September 2015, HCV sequence analysis was performed in order to confirm commercial LiPA-HCV genotype (Versant ® HCV Genotype 2.0) in patients eligible for treatment with DAAs. Out of 134 consecutive patients enrolled, sequencing yielded 21 (15.7%) cases of discordant results. For three cases of wrong genotype assignment, the putative reduction in efficacy was gauged between 15% and 40%. Among the eight cases for whom G1b was assigned by commercial assays instead of G1a, potentially suboptimal treatments would have been prescribed. Finally, for five patients with G1 and indeterminate subtype, the choice of regimens would have targeted the worst option, with a remarkable increase in costs, as in the case of the four mixed HCV infections for whom pan-genotypic regimens would have been mandatory. Precise assignment of HCV genotype and subtype by sequencing may, therefore, be more beneficial than expected, until more potent pan-genotypic regimens are available for all patients.

Background: Since the HLA-B*57:01 allele is strongly associated with abacavir hypersensitivity reaction, testing for the presence of HLA-B*57:01 is mandatory before administration of abacavir. While HLA-B*57:01 testing is usually provided by pharmacogenetics, genetics or blood transfusion services, clinical virology laboratories can be an optimal opportunity for HLA-B*57:01 testing since they receive blood samples for routine HIV monitoring and have the expertise for convenient and less expensive PCR-based point mutation assays., Objectives: The Italian HLA-B*57:01 Network gathers accredited clinical virology laboratories offering HLA-B*57:01 testing in Italy with the aim to share protocols, test new methods, develop and maintain external quality assurance (EQA) programs., Study Design: A panel of 9HLA-B*57:01-positive and 16HLA-B*57:01-negative frozen blood samples were blindly distributed to 10 units including 9 clinical virology laboratories and one reference pharmacology laboratory. Each laboratory was free to use its own routine method for DNA extraction and HLA-B*57:01 testing., Results: DNA was extracted by automated workstations in 6 units and by manual spin columns in 4. Eight units used the Duplicα Real Time HLA-B*57:01 kit by Euroclone and two units used two different PCR homemade protocols. All the 10 units correctly identified all the 25 samples., Conclusions: The first HLA-B*57:01 EQA program run in Italy showed that clinical virology units are equipped and proficient for providing HLA-B*57:01 testing by inexpensive assays easy to integrate into their routine., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: Available estimates of the prevalence of chronic HCV infection in Italy are quite conflicting, varying from 1.5 to 22.5%, with an apparent north to south gradient. As Direct Acting Antivirals are expensive, both National and local governmental Agencies are in urgent need of detailed and reliable estimates of HCV patients to be treated, nationwide and in each district. We investigated the prevalence of anti-HCV antibodies in a large unselected sample of surgical patients providing consent to in-hospital opt-out pre-surgical HCV screening, at two hospitals from the Abruzzo Region, Italy., Methods: Data were retrieved for 55,533 screened patients (4.1% of the total population in the Abruzzo Region), admitted in the Orthopedic and General Surgery wards of Pescara and Teramo Hospitals from 1999 to 2014., Results: The prevalence of anti-HCV antibodies was 4.4% in the total sample. HCV-positive patients had a mean age of 63.8 ± 19.9 years; 49.2% were males. From 1999 to 2014, the prevalence of HCV antibodies decreased from 5.4% to 4.1%; at both sites, however, two age-related-peaks were evidenced, the first among patients aged 30-49 years, the second among those older than 70 years. Statistical analyses confirmed a significant trend to decrease over time and a higher prevalence in Pescara and among males (all p < 0.01)., Conclusions: Data retrieved from opt-out pre-surgical screening programs may allow inexpensive and easy-to-perform estimates of HCV seroprevalence from large samples of unselected patients with a well-defined provenience, which may turn useful for future treatment resource allocation.

The importance of nosocomial infections caused by coagulase-negative staphylococci is constantly growing. The threat primarily affects immunocompromised patients, the elderly and neonates, particularly after invasive surgery. The problem is fundamentally exacerbated by expanding antibacterial drug resistance. A case report is presented of an 86-year-old patient who underwent a ruptured abdominal aortic aneurysm surgery and developed septicaemia upon surgical wound infection. The causal agent was likely a carbapenem-resistant Klebsiella pneumoniae, however, daptomycin-resistant Staphylococcus pettenkoferi was identified in blood cultures in the absence of daptomycin treatment. To the authors' knowledge, the case study presented is the first published episode of daptomycin-resistant S. pettenkoferi strain.

When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.

Low bone mineral density (BMD) is frequent in HIV infection regardless of the use of antiretroviral therapy (ART). Uncertainties remain, however, as to when in HIV infection BMD screening should be performed. We designed a prospective study to estimate the efficacy of universal BMD screening by dual-energy X-ray absorptiometry (DXA). Since April 2009 through March 2011, HIV patients attending our Center were offered femoral/lumbar DXA to screen BMD. Low BMD for chronological age, that is significant osteopenia, was defined as a Z-score ≤ -2.0 at femur and lumbar spine. Nontraumatic bone fractures (NTBFs) were evaluated. The final sample included 163 patients. A Z-score ≤ -2.0 at any site was observed in 19.6% of cases: among these, 18.8% had no indication to DXA using current Italian HIV guidelines for BMD screening. A lower femoral Z-score was independently associated with lower BMI, AIDS diagnosis, HCV co-infection, antiretroviral treatment, and NTBFs; a lower lumbar Z-score with age, BMI, Nadir CD4 T-cell counts, and NTBFs. Prevalence of NTBFs was 27.0%, predictors being male gender, HCV co-infection, and lower femoral Z-scores. Our results suggest that measuring BMD by DXA in all HIV patients regardless of any further specification may help retrieving one-fifth of patients with early BMD disorders not identified using current criteria for selective screening of BMD.

Background: As HIV infection turned into a chronic treatable disease, now ranking as one of the most costly in medicine, long-term sustainability of highly active antiretroviral treatment (HAART) expenses became a major issue, especially in countries with universal access to care. Identification of determinants of higher HAART costs may therefore help in controlling costs of care, while keeping high levels of retention in care and viral suppression., Methods: With this aim, we enrolled a large multicentric sample of consecutive unselected human immunodeficiency virus (HIV) patients followed at five sites of care in Italy, and evaluated annual individual HAART costs in relation to a number of sociodemographic, clinical, and laboratory variables., Results: We enrolled 2,044 patients, including 1,902 on HAART. Mean HAART costs were €9,377±€3,501 (range 782-29,852) per year, with remarkable site-based differences, possibly related to the different composition of local assisted populations. Percentages of patients on viral suppression were homogeneously high across all study sites. The factors identified by cross-validation were line of HAART, diagnosis of acquired immune deficiency syndrome, current CD4 T-cell count, and detectable HIV viremia >50 copies/mL. In the final multivariable model, HAART costs were independently directly associated with more advanced HAART line (P<0.001) and inversely correlated with current CD4 T-cell count (P=0.024). Site of care held independent prediction of higher costs, with marked control of expenses at sites 2 (P=0.001) and 5 (P<0.001)., Conclusion: Higher costs of HAART were strongly associated with previous treatment failures, detectable HIV viremia, and lower CD4 T-cell count at the time of evaluation, with no correlation at all with sex, age, hepatitis C virus coinfection, and nadir CD4 T-cell counts. Newer drugs, which are typically those associated with high prices, at the time of the analysis were still prevalently prescribed to rescue and maintain viral suppression in patients with more complex treatment history. Further analyses of the contribution of the single drug/regimen to the estimated cost are warranted.

Purulent infection of a surgical wound developed after discectomy, and a mannitol-nonfermenting Staphylococcus aureus isolate was cultivated as the etiologic agent. Nonfermenting S. aureus strains are exceedingly rare and may be erroneously mistaken and dismissed as contaminants. This report then emphasizes that pure and massive cultures must be carefully evaluated, even if preliminary examination does not suggest a pathogenic organism. Also, although mannitol-negative, the studied strain was correctly detected as S. aureus by both the-FISH test (AdvanDx, USA) and the Liofilchem 'Chromatic Staph aureus', highlighting that additional diagnostic methods may support recognition of uncommon, nonfermenting S. aureus strains in the daily practice.

We first observed the phenomenon of small colony variants (SCVs) in a Staphylococcus pseudintermedius sequence type 71 (ST71) strain, isolated from a non-pet owner. Although we found that small-sized colonies share main features with Staphylococcus aureus SCVs, they nevertheless show a novel, particular, and sticky phenotype, whose expression was extremely stable, even after subcultivation.

The treatment of visceral leishmaniasis (VL) is poorly standardized in Italy in spite of the existing evidence. All consecutive patients with VL admitted at 15 Italian centers as inpatients or outpatients between January 2004 and December 2008 were retrospectively considered; outcome data at 1 year after treatment were obtained for all but 1 patient. Demographic characteristics, underlying diseases, diagnostic procedures, treatment regimens and outcomes, as well as side effects were recorded. A confirmed diagnosis of VL was reported for 166 patients: 120 (72.3%) immunocompetent, 21 (12.6%) patients with immune deficiencies other than HIV infection, and 25 (15.1%) coinfected with HIV. Liposomal amphotericin B (L-AmB) was the drug almost universally used for treatment, administered to 153 (92.2%) patients. Thirty-seven different regimens, including L-AmB were used. The mean doses were 29.4 ± 7.9 mg/kg in immunocompetent patients, 32.9 ± 8.6 mg/kg in patients with non-HIV-related immunodeficiencies, and 40.8 ± 6.7 mg/kg in HIV-infected patients (P < 0.001). The mean numbers of infusion days were 7.8 ± 3.1 in immunocompetent patients, 9.6 ± 3.9 in non-HIV-immunodeficient patients, and 12.0 ± 3.4 in HIV-infected patients (P < 0.001). Mild and reversible adverse events were observed in 12.2% of cases. Responsive patients were 154 (93.3%). Successes were 98.4% among immunocompetent patients, 90.5% among non-HIV-immunodeficient patients, and 72.0% among HIV-infected patients. Among predictors of primary response to treatment, HIV infection and age held independent associations in the final multivariate models, whereas the doses and duration of L-AmB treatment were not significantly associated. Longer treatments and higher doses of L-AmB were not able to significantly modify treatment outcomes either in the immunocompetent or in the immunocompromised population.

Immunoglobulins are one major component of adaptive immunity to external and resident microorganisms, evolving very early in phylogenesis. They help eukaryotes in controlling infections, mainly through their neutralizing activity, which quenches both the cytopathic and inflammatory potential of invading microorganisms. Cytomegalovirus (CMV)-related disease is generally blunted in seropositive subjects with conserved specific humoral responses. CMV-seropositive pregnant women, in accordance with such evidence, suffer little or no fetal damage when reexposed to CMV. Several seminal experiences and early experimental models confirmed that repeated infusions of immunoglobulins, either with hyperimmune or standard preparations, may help to reduce maternal-fetal CMV transmission, as well as to quench fetal disease upon transmission. This review focused on experimental evidence supporting the potential role of immunoglobulins as a tool to control fetal CMV-related disease in pregnant women.

The prevalence of drug resistance associated with the failure of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and the predictors of resistance to Etravirine (ETR) were assessed in 2854 subjects: 39 < 18 (paediatric) and 2815 ≥ 18 (adult) years old. These subjects failed to respond to their current NNRTI treatment, were three-class experienced and had been exposed to NNRTI for ≥3 months. A total of 1827 adult (64.9%) and 32 paediatric subjects (82.1%) harboured the virus with at least one ETR mutation. V179I, Y181C and G190A were the most frequent mutations in both groups. A significantly increased risk of ETR resistance with all three algorithms (Monogram (MGR) >3, Tibotec (TBT) >2 and enhanced MGR (ENH) ≥4) emerged in the paediatric population. Multivariate analysis revealed an increased risk of developing TBT >2 for NNRTI exposure, ENH ≥4 for NNRTI and EFV exposure in paediatric subjects; NVP exposure and higher (≥3.5 log10) HIV-RNA values for all three algorithms in adult subjects, whereas CD4 ≥ 200/μL appeared to be protective. The risk of being ETR resistant was more than doubled for paediatric vs. adult subjects, probably due to a more extensive use of NNRTI and an incomplete virological control., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Staphylococcus pseudintermedius is a veterinary pathogen that has seldom been described as an agent of human disease. Features of this probably underreported coagulase-positive Staphylococcus species are depicted here through the description of a graft-versus-host disease-related wound infection caused by a multidrug-resistant strain.

A yeast strain was isolated from the sputum sample of a leukaemia patient in the Spirito Santo Hospital of Pescara, Italy. The fungus produced a pigment that formed a reddish halo around colonies, and was identified and deposited as a Metschnikowia spp. (accession number IHEM 25107-GenBank accession number JQ921016) in the BCCM/IHEM collection of biomedical fungi and yeasts (Bruxelles, Belgium). Although the physiology of the strain was close to that of Metschnikowia sinensis, the D1/D2 sequence did not correspond to any previously described Metschnikowia species. Phylogeny of the genus Metschnikowia is complex and requires far more analysis. We present the first non-M. pulcherrima Metschnikowia spp. isolate recovered from a human, and emphasize the role of man as a transient carrier of environmental yeasts, the pathogenicity of which still needs to be defined.