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HCV infection poses a global health threat, with significant morbidity and mortality. This study examines HCV trends in a large Italian region from 2015 to 2022, considering demographic changes, evolving clinical profiles, treatment regimens and outcomes, including the impact of the COVID-19 pandemic. This multicentre retrospective study analysed demographics, clinical histories and risk factors in 6882 HCV patients. The study spanned before and after the direct-acting antiviral (DAA) era, and the COVID-19 period, focusing on treatment outcomes (SVR12, non-SVR12 and patients lost to follow-up). Statistical methods included ANOVA, multinomial logistic regression, Kruskal-Wallis test and chi-square analysis, and were conducted adhering to the intention-to-treat (ITT) principle. The cohort, mainly Italian males (average age 58.88), showed Genotype 1 dominance (56.6%) and a high SVR12 rate (97.5%). The pandemic increased follow-up losses, yet SVR12 rates remained stable, influenced by factors like age, gender, cirrhosis and comorbidities. Despite COVID-19 challenges, the region sustained high SVR12 rates in HCV care, emphasising the importance of sustained efforts in HCV care. Continuous screening and targeted interventions in high-risk populations are crucial for achieving WHO elimination targets. The study highlights the resilience of HCV care during the pandemic and provides insights for future public health strategies., (© 2024 The Author(s). Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Human leishmaniasis is facing important epidemiological changes in Southern Europe, driven by increased urbanization, climate changes, emerging of new animal reservoirs, shifts in human behavior and a growing population of immunocompromised and elderly individuals. In this evolving epidemiological landscape, we analyzed the clinical and epidemiological characteristics of human leishmaniasis in the Tuscany region of Central Italy. Through a multicentric retrospective analysis, we collected clinical and demographic data about all cases of leishmaniasis recorded between 2018 and 2023. We observed 176 cases of human leishmaniasis, with 128 (72.7%) visceral leishmaniasis (VL) and 47 (26.7%) cutaneous leishmaniasis (CL). Among these, 92.2% of VL and 85.1% of CL cases were autochthonous. The cumulative incidence of autochthonous human leishmaniasis was 0.22 cases per 100,000 inhabitants in 2018, but reached 1.81/100,000 in 2023. We identified three main areas of transmission: around the city of Florence (North-East Tuscany), around Grosseto city (South-West Tuscany) and Elba Island. Our findings confirm that the epidemiology of leishmaniasis is undergoing significant changes in Central Italy. Awareness towards this emerging health threat and surveillance strategies need to be improved in order to reliably assess the disease's burden. Further research is needed in a "One-Health" perspective, to clarify the epidemiological dynamics at the environmental, reservoir, vector and human levels. The role of climate change and specific climatic factors affecting the epidemiological patterns of human leishmaniasis should be assessed. Further knowledge in these fields would promote targeted control and prevention strategies at regional and national levels.

Background: A few months after the COVID-19 pandemic onset, knowledge of SARS-CoV-2 infection and outcomes and treatments blew up. This paper aimed to evaluate the features of a Tuscany COVID-19 hospitalized cohort and to identify risk factors for COVID-19 severity. Methods: This retrospective observational COVID-19 cohort study (1 March 2020-1 March 2021) was conducted on patients ≥ 18 years old, admitted to Tuscany Hospital, and subjected to follow-up within 12 months after discharge. Patients were enrolled at Pisana, Senese and Careggi University Hospitals, and South East, North West, and Center Local Hospitals. Results : 2888 patients (M = 58.5%, mean age = 66.2 years) were enrolled, of whom 14.3% (N = 413) were admitted to an intensive care unit. Smokers were 25%, and overweight and obese 65%. The most used drugs were corticosteroids, antacids, antibiotics, and antithrombotics, all antiviral drugs, with slight differences between 2020 and 2021. A strong association was found between outcomes of evolution towards critical COVID-19 (non-invasive mechanical ventilation (NIV) and/or admission to intensive care) and smoking (RR = 4.91), ex-smoking (RR = 3.48), overweight (RR = 1.30), obese subjects (RR = 1.62), comorbidities (aRR = 1.38). The alteration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyl transpeptidase) was associated with NIV (aOR = 2.28). Conclusions: Our cohort, characterized by patients with a mean age of 66.2 years, showed 65% of patients were overweight and obese. Smoking/ex-smoking, overweight/obesity, and other comorbidities were associated with COVID-19 adverse outcomes. The findings also demonstrated that alterations in liver enzymes were associated with worse outcomes.

Purpose: Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration., Methods: We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments., Results: During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%)., Conclusion: In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections., (© 2024. The Author(s).)

Italy is recognized as having the highest Hepatitis C virus (HCV) prevalence in Europe. The Tuscany region, where the prevalence of HCV infection is approximately 0.8%, implemented two programs for the control of chronic hepatitis C in Tuscany from 2018 to 2022. This retrospective study aims to investigate the incidence of HCV in a population screened in Southeastern Tuscany from 2013 to 2022. The study population included 246,137 patients from the provincial area of Arezzo and Grosseto, Tuscany, spanning from January 2013 to October 2022. Among the subjects included in the study, 3,190 (1.29%) tested positive for anti-HCV antibodies. Of this population, 2,119 patients (66.43%) also tested positive for HCV-RNA quantification, leading to their enrolment for subsequent viral genotyping. 1,106 patients had genotype (GT) 1 (52.2%), 484 had GT 3 (22.8%), 371 had GT 2 (17.5%), and 158 had GT 4 (7.5%). Our study underscores the prevalence of HCV GTs 1 and 3 as the most predominant GTs in the Southeast Tuscany region. We also observe a correlation between age, sex and HCV genotypic distribution.

Introduction: Inertial Measurement Units (IMU) require a sensor-to-segment calibration procedure in order to compute anatomically accurate joint angles and, thereby, be employed in healthcare and rehabilitation. Research literature proposes several algorithms to address this issue. However, determining an optimal calibration procedure is challenging due to the large number of variables that affect elbow joint angle accuracy, including 3D joint axis, movement performed, complex anatomy, and notable skin artefacts. Therefore, this paper aims to compare three types of calibration techniques against an optical motion capture reference system during several movement tasks to provide recommendations on the most suitable calibration for the elbow joint. Methods: Thirteen healthy subjects were instrumented with IMU sensors and optical marker clusters. Each participant performed a series of static poses and movements to calibrate the instruments and, subsequently, performed single-plane and multi-joint tasks. The metrics used to evaluate joint angle accuracy are Range of Motion (ROM) error, Root Mean Squared Error (RMSE), and offset. We performed a three-way RM ANOVA to evaluate the effect of joint axis and movement task on three calibration techniques: N-Pose (NP), Functional Calibration (FC) and Manual Alignment (MA). Results: Despite small effect sizes in ROM Error, NP displayed the least precision among calibrations due to interquartile ranges as large as 24.6°. RMSE showed significant differences among calibrations and a large effect size where MA performed best (RMSE = 6.3°) and was comparable with FC (RMSE = 7.2°). Offset showed a large effect size in the calibration*axes interaction where FC and MA performed similarly. Conclusion: Therefore, we recommend MA as the preferred calibration method for the elbow joint due to its simplicity and ease of use. Alternatively, FC can be a valid option when the wearer is unable to hold a predetermined posture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bonfiglio, Tacconi, Bongers and Farella.)

Chronic pain is a condition in which the use of digital health technologies, ecological momentary assessments, and digital communication tools may boost patient's engagement and coping. Here we present the results of the PainRE-Life a project, financed by the Lombardy Region (Italy), aimed to develop a dynamic and integrated technology ecosystem based on big data management and analysis to allow care continuity in patients with pain, and able to act as a decision aid for patients and caregivers.

Background: Comparative data on mortality in COVID-19 patients treated with molnupiravir or with nirmatrelvir plus ritonavir are inconclusive. We therefore compared all-cause mortality in community-dwelling COVID-19 patients treated with these drugs during the Omicron era., Methods: Data collected in the nationwide, population-based, cohort of patients registered in the database of the Italian Medicines Agency (AIFA) were used. To increase completeness of the recorded deaths and date correctness, a cross-check with the National Death Registry provided by the Ministry of the Interior was performed. We included in this study all patients infected by SARS-CoV-2 treated within 5 days after the test date and symptom onset between February 8 and April 30, 2022. All-cause mortalities by day 28 were compared between the two treatment groups after balancing for baseline characteristics using weights obtained from a gradient boosting machine algorithm., Findings: In the considered timeframe, 17,977 patients treated with molnupiravir and 11,576 patients with nirmatrelvir plus ritonavir were included in the analysis. Most patients (25,617/29,553 = 86.7%) received a full vaccine course including the booster dose. A higher crude incidence rate of all-cause mortality was found among molnupiravir users (51.83 per 100,000 person-days), compared to nirmatrelvir plus ritonavir users (22.29 per 100,000 person-days). However, molnupiravir-treated patients were older than those treated with nirmatrelvir plus ritonavir and differences between the two populations were found as far as types of co-morbidities were concerned. For this reason, we compared the weight-adjusted cumulative incidences using the Aalen estimator and found that the adjusted cumulative incidence rates were 1.23% (95% CI 1.07%-1.38%) for molnupiravir-treated and 0.78% (95% CI 0.58%-0.98%) for nirmatrelvir plus ritonavir-treated patients (adjusted log rank p = 0.0002). Moreover, the weight-adjusted mixed-effect Cox model including Italian regions and NHS centers as random effects and treatment as the only covariate confirmed a significant reduced risk of death in patients treated with nirmatrelvir plus ritonavir. Lastly, a significant reduction in the risk of death associated with nirmatrelvir plus ritonavir was confirmed in patient subgroups, such as in females, fully vaccinated patients, those treated within day 2 since symptom onset and patients without (haemato)-oncological diseases., Interpretation: Early initiation of nirmatrelvir plus ritonavir was associated for the first time with a significantly reduced risk of all-cause mortality by day 28 compared to molnupiravir, both in the overall population and in patient subgroups, including those fully vaccinated with the booster dose., Funding: This study did not receive funding., Competing Interests: PPO, SC, VS, PR, Giorgio Palù, Carlo Torti, AS, AV, DT, ET, AP, CB, AG, EME, MF, GBB and ML report no competing interests regarding this article. PB reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Viiv, Gilead, Jannsen, Merck and Pfizer. CT reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Gilead, Merck, Pfizer, Menarini, GSK, Sanofi, Angelini, thermofischer, Biotest and Diasorin. EN reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Gilead, Eli Lilly, Roche, SOBI. BC reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Angelini, Menarini. Giustino Parruti reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Gilead, Merck, AlphaSigma, Angelini, Pfizer, Lusofarmaco, GSK, Janssen. MB reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Angelini, BioMérieux, Cidara, Menarini, MSD, Pfizer and Shionogi. GDP reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from GS, MSD, ViiV, Abbvie, Janssen, GSK, AZ, Pfizer, Roche., (© 2023 The Author(s).)

Introduction: In early to mid-2022, an unexpected outbreak of Monkeypox virus infections occurred outside the African endemic regions. Vaccines originally developed in the past to protect against smallpox are one of the available countermeasures to prevent and protect against Orthopoxvirus infections. To date, there are few studies on the cross-reactivity of neutralizing antibodies elicited by previous vaccinia virus-based vaccination and/or Monkeypox virus infection. The aim of this study was to evaluate a possible approach to performing Monkeypox and vaccinia live-virus microneutralization assays in which the read-out is based on the production of cytopathic effect in the cell monolayer., Methods: Given the complexity of Orthopoxviruses, the microneutralization assay was performed in such a way as to uncover a potential role of complement, with and without the addition of an external source of Baby Rabbit Complement. A set of human serum samples from individuals who had been naturally infected with Monkeypox virus and individuals who may have and not have undergone vaccinia virus vaccinations, was used to evaluate the performance, sensitivity, and specificity of the assay., Results and Conclusions: The results of the present study confirm the presence and cross-reactivity of antibodies elicited by vaccinia-based vaccines, which proved able to neutralize the Monkeypox virus in the presence of an external source of complement., Competing Interests: AM, NS, PC, LM, GP, and MB were employed by VisMederi srl. LB and ML were employed by VisMederi Research srl. EM was founder and chief scientific officer of VisMederi srl and VisMederi Research srl. CT was an external consultant of VisMederi Research srl. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Manenti, Solfanelli, Cantaloni, Mazzini, Leonardi, Benincasa, Piccini, Marchi, Boncioli, Spertilli Raffaelli, Tacconi, Mattiuzzo, Kistner, Montomoli and Trombetta.)

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Background and Aims: The aim of this study was to evaluate the diagnostic accuracy of sepsis markers and to develop a multiparametric score, using demographic and clinical variables as well as laboratory parameters to predict sepsis in patients admitted in the ED with suspected symptoms., Materials and Methods: Patients with clinical presentation of suspected sepsis were enrolled in the ED of San Donato Hospital in Arezzo between September 2019 and May 2020. Anagraphic, anamnestic, clinical and laboratory data were collected for all subjects. PCT, MDW, WBC, MPV and BT were utilised to formulate FANS score., Results: The AUC of the FANS score, PCT, MDW and CRP was 0.87, 0.80, 0.77 and 0.71, respectively, when used to predict sepsis in all 308 subjects. Instead, the AUC of the FANS (Fighting Action To Neutralize Sepsis) score, PCT, MDW and CRP was 0.93, 0.84, 0.83 and 0.77, respectively, when used to predict sepsis excluding subjects with infection (clinically classified as the Infections group)., Conclusions: The results obtained with PCT, PCR and MDW confirm the results of these markers for the identification of sepsis obtained from other studies. The multiparametric approach, obtained from the statistical study of the parameters using binary logistic regression, identified those PCT, WBC, MPV, BT and MDW as the most significant and effective clinical classifiers for diagnosing sepsis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Since May 2022, an outbreak of monkeypox has been ongoing in non-endemic countries. We report four cases in Italy in young adult men reporting condomless sexual intercourse. The patients are in good clinical condition with no need for specific antiviral drugs. Biological samples from seminal fluid were positive for monkeypox viral DNA. For many other viruses found in semen there is no evidence of sexual transmission. The possibility of sexual transmission of monkeypox virus needs to be investigated.

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.

The new parameter derived from the standard deviation of the monocyte distribution width (MDW) has shown a good diagnostic efficacy in COVID-19 patients. In this study, we propose MDW as a prognostic and monitoring parameter in patients with severe forms of COVID-19. Sixty SARS-CoV-2-positive patients admitted to the San Donato Hospital in Arezzo were enrolled. A blood sample taken to measure the complete blood count was used for the determination of MDW using a UniCel DxH 900 instrument (Beckman Coulter). For each patient, a mean of 6 ± 2 measurements of MDW were taken. The difference between the last and first MDW results was reported as the ΔMDW variable. The ΔMDW and age were significantly correlated to the outcome. In non-survivors patients, the difference in the mean of the MDW between the first and other points was not significant, while in survivors, the first point was higher than the other points (p < 0.005), with the exception of the mean of the second point (p-value = NS). The ΔMDW area under the curve (AUC) was 0.84, and with a cut-off lower than 0.00 the sensitivity and specificity were 88% and 81%, respectively. The most important result of this study is the ΔMDW calculated on the basis of the difference between the first and third measurement, after approximately the 5-7th day of hospitalisation. A ΔMDW less than one was indicative of an unfavourable prognosis. The data reported suggest that MDW could be used to support monitoring and surveillance, alongside other tests such as procalcitonin, in critically ill patients in the ICU., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: The aim of this study was to evaluate the risk of hospitalization or death in patients infected by SARS-CoV2 variants of concern (VOCs) receiving combinations of monoclonal antibodies (mAbs), bamlanivimab/etesevimab or casirivimab/imdevimab., Methods: Observational prospective study conducted in two Italian hospitals (University Hospital of Pisa and San Donato Hospital, Arezzo) including consecutive outpatients with COVID-19 who received bamlanivimab/etesevimab or casirivimab/imdevimab from March 20th to May 10th 2021. All patients were at high risk of COVID-19 progression according to FDA/AIFA recommendations. Patients were divided into two study groups according to the infecting viral strain (VOCs): Alpha and Gamma group. The primary endpoint was a composite of hospitalization or death within 30 days from mAbs infusion. A Cox regression multivariate analysis was performed to identify factors associated with the primary outcome in the overall population., Results: The study included 165 patients: 105 were infected by the VOC Alpha and 43 by the VOC Gamma. In the Alpha group, no differences in the primary endpoint were observed between patients treated with bamlanivimab/etesevimab or casirivimab/imdevimab. Conversely, in the Gamma group, a higher proportion of patients treated with bamlanivimab/etesevimab met the primary endpoint compared to those receiving casirivimab/imdevimab (55% vs. 17.4%, p = 0.013). On multivariate Cox-regression analysis, the Gamma variant and days from symptoms onset to mAbs infusion were factors independently associated with higher risk of hospitalization or death, while casirivimab/imdevimab was protective (HR 0.33, 95% CI 0.13-0.83, p = 0.019)., Conclusions: In patients infected by the SARS-CoV-2 Gamma variant, bamlanivimab/etesevimab should be used with caution because of the high risk of disease progression., (© 2021. The Author(s).)

Background: Scrub typhus is a vector-borne rickettsial infection, which can cause relevant morbidity and mortality. While the number of cases is around a million per year globally, the infection is seldom diagnosed in travellers from Europe., Methods: We herein report three cases diagnosed in Italian travellers and review the literature about imported cases in Europe in the last 60 years., Results: Three participants to the same hiking trip to the forest of northern Laos presented fever and other symptoms, including eschars (2 individuals) and skin rash (2 individuals). Overall, they didn't report complications, and recovered soon after doxycycline treatment. Diagnosis was retrospectively confirmed with PCR in one of them. The review collected data from 40 patients. Almost all of them (95%) presented fever, more than a half had headache, skin rash, eschars, arthromyalgias. 73% of them were hospitalized, and 16.2% needed intensive care. Diagnosis was confirmed by serology in almost all cases (94.6%). Most patients (88%) were treated with doxycycline. All patients survived, although one case resulted in incomplete tetraparesis., Conclusions: Scrub typhus should be considered in all travellers coming back from endemic areas and presenting with acute febrile illness. Laboratory diagnosis can be challenging, as specific tests are not widely available. In case of clinical suspicion, a prompt treatment with oral doxycycline could avoid severe complications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group ( p = 0.0037). The Kaplan-Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group ( p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group ( p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group ( p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.

Introduction: Interesting results regarding the contribution of MDW (Monocyte Distribution Width) in the Infectious Disease Unit have been reported. An observational study is ongoing at San Donato Hospital with the aim to evaluate the contribution of MDW in the diagnostic pathway in adult patients entering in the ED setting and tested for SARS-CoV-2., Material and Method: COVID-19 symptomatic and paucisymptomatic patients presenting to ED (Emergency Department), have been enrolled consecutively. Whole blood venous samples have been collected on K2 EDTA for MDW determination, at the same time a nasopharyngeal swab for SARS-CoV-2 RNA detection have been collected., Results: One hundred six patients were negative for SARS-CoV-2 with MDW mean value of 20.3 ± 3.3, while forty-one were positive for SARS-CoV-2 with higher MDW mean value of 27.3 ± 4.9 (P < 0.005). The ROC curve analysis has been evaluated showing MDW AUC of 0.91. Finally twenty-three patients hospitalized in high-intensity care unit showed an MDW value higher than the eighteen patients presenting few symptoms [28.8 ± 5.3 vs 25.4 ± 3.6 respectively, P < 0.05]., Discussion: Monocytic population, in Covid19 disease, are the first elements of innate immunity to be involved, these changes are the basis of the modification of the MDW, with evident efficacy in term of sensitivity, particularly in the studied Covid19 patients. Moreover the patients hospitalized in high-intensity care unit showed significantly elevated MDW respects to middle or low symptomatic one, suggest including this parameter as prognostic marker or of therapy efficacy, integrated with other laboratory findings., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Since February 2020, Italian hospitals registered COVID-19 (COronaVIrus Disease 19) cases more often than the rest of the Europe. During this epidemic, health authorities requested swab tests, while seeking new patient paths., Methods: A dual laboratory approach was evaluated, consisting of patient care reports for viral RNA detection on swabs and rapid serological tests in 516 patients (192 symptomatic or paucisymptomatic and 324 asymptomatic)., Results: We found the molecular positive fraction equal to 12% (23/192) among symptomatic/paucisymptomatic (S/P) and 15.4% (50/324) in asymptomatic (As) sets. Among subsets, we observed serologically positive results, corresponding to 35% (8/23) for S/P and 38% (19/50) for As. Among molecular negative cases, we detected specific Immunoglobulin G or M (Ig G or Ig M) positivity in the S/P cohort equal to 6.6% (11/167) and 6% (15/246) in As cases. For indeterminate molecular results, we found S/P serological positivity equal to 100% (1/1) and 54% (13/24) in As patients. We found higher (p < 0.05) seropositivity in older patients (n = 8) among symptomatic and positives for viral RNA (n.23)., Conclusions: It has been observed that a dual approach of serological and molecular tests detects a higher absolute number of disease cases in a pandemic context,which could improve monitoring and health surveillance efficacy. The age-related seropositivity frequency in this study, if confirmed, could enhance the validity of serological tests, especially in older patients.In these subjects, molecular positivity accompanied by serological positivity (distinct for M and G immunoglobulins) should help determine disease status and support decisions related to patient management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) have increased since November 2018. Between November 2018 and October 2019, 1,645 samples were NDM-CRE-positive: 1,270 (77.2%) cases of intestinal carriage, 129 (7.8%) bloodstream infections and 246 (14.9%) infections/colonisations at other sites. Klebsiella pneumoniae were prevalent (1,495; 90.9%), with ST147/NDM-1 the dominant clone. Delayed outbreak identification and response resulted in sustained NDM-CRE transmission in the North-West area of Tuscany, but successfully contained spread within the region.

Background: Mortality in patients with type 2 diabetes and diabetic foot osteomyelitis (DFO) have been explored in few small studies with a short follow-up. Aim of the present study is to assess all-cause and cardiovascular mortality and predictors of mortality in a consecutive series of patients with DFO., Research Design and Methods: Patients with a diagnosis of DFO, attending the Diabetic Foot Unit of San Donato Hospital in Arezzo between January 1st, 2012 and December 31st, 2013, were included in this retrospective study. Information on all-cause mortality up to December 1st, 2016, was obtained from the registry of the Local Health Unit of Arezzo, which contains updated records of all persons living in Tuscany., Results: One hundred ninety-four patients were included in the study. During a mean period of observation of 2.8±1.4years, 73 (37.6%) died, with a yearly rate of 13.2%. Of the 73 deaths, 59 were attributable to cardiovascular causes. After adjusting for possible confounders in a Cox analysis, site of osteomyelitis (hindfoot vs mid/forefoot) was associated with a higher mortality, and surgical treatment with a lower mortality., Conclusions: Mortality in patients with DFO appears to be much higher than that reported in clinical series of patients with diabetic foot ulcers, particularly when hindfoot is affected., (Copyright © 2017. Published by Elsevier B.V.)

A total of 81 HIV-1 protease (PR) and reverse transcriptase (RT) sequences were obtained from 46 drug-naive and 35 pretreated individual HIV-1-infected orphaned children followed at a donor-funded rural pediatric clinic in Dodoma, Tanzania. PR and RT sequencing was performed by home-brew technology on 70 plasma samples and 11 dried blood spot specimens. Nucleoside RT inhibitor (NRTI) resistance mutations were detected in 2.2% of drug-naive and 82.9% of pretreated children. Nonnucleoside RT inhibitor (NNRTI) resistance mutations were detected in 69.6% of drug-naive and 91.4% of pretreated children. Resistance to protease inhibitors was rare (8.6% in pretreated children). Based on few complete treatment records, only around 20% of the treated children had undetectable plasma HIV-1 RNA. The rate of NRTI and NNRTI resistance in this donor-funded rural pediatric clinic was high and appeared to limit virological response to treatment.

This report focuses on epidemiological and clinical features of dengue fever (DF) in Tuscany (Italy) between 2006 and 2012. Sixty-one DF cases were diagnosed, 32 of which were in the period of Aedes albopictus activity. Some clinical (arthralgia/myalgia, nausea/vomiting, and skin rash), laboratory (leukopenia and thrombocytopenia), and epidemiological characteristics (travel in a continent other than Africa) significantly distinguished DF cases from other febrile illnesses. Our data stress the importance of increasing awareness on dengue in Italy among clinicians in order to reach an early diagnosis in returning travelers and to implement appropriate clinical and public health interventions., (© 2014 International Society of Travel Medicine.)

The principal conditions requiring emergency/urgent intervention in patients with nontraumatic liver lesions are hemorrhage (with or without tumor rupture), rupture of hydatid cysts (with or without infection), complications arising from liver abscesses or congenital liver cysts, rupture related to peliosis hepatis, and in rare cases spontaneous hemorrhage. This article examines each of these conditions, its appearance on ultrasound (the first-line imaging method of choice for assessing any urgent nontraumatic liver lesion) and indications for additional imaging studies.

Objective: Development of critical limb ischemia (CLI) has been reported as an independent predictor of cardiac mortality in diabetic patients. We aimed to determine whether CLI, managed in a structured setting of close collaboration between different vascular specialists and treated with early endovascular intervention, has any impact on long-term cardiac mortality of diabetic patients initially presenting with symptomatic coronary artery disease (CAD)., Research Design and Methods: We designed a prospective observational study of 764 consecutive diabetic patients undergoing percutaneous coronary intervention (PCI) in whom development of CLI was assessed by a dedicated diabetic foot clinic. Cardiac mortality at 4-year follow-up was the primary end point of the study., Results: Among the 764 patients, 111 (14%) developed CLI (PCI-CLI group) and underwent revascularization of 145 limbs, with procedural success in 140 (96%). PCI-CLI patients at baseline had lower left ventricular ejection fraction (51 ± 11% vs. 53 ± 10%, P = 0.008), higher prevalence of dialysis (7% vs. 0.3%, P < 0.0001), and longer diabetes duration (13 ± 8 vs. 11 ± 7 years, P = 0.02) compared with PCI-only patients. At 4-year follow-up, cardiac mortality occurred in 10 (9%) PCI-CLI patients vs. 42 (6%) PCI-only patients (P = 0.2). Time-dependent Cox regression model for cardiac death revealed that CLI was not associated with an increased risk of cardiac mortality (hazard ratio 1.08 [95% CI 0.89-3.85]; P = 0.1)., Conclusions: The development of promptly assessed and aggressively treated CLI was not significantly associated with increased risk of long-term cardiac mortality in diabetic patients initially presenting with symptomatic CAD.

Ultrasound (US) imaging of the spleen was considered of little use in the past and was performed only to distinguish between cystic and solid lesions. However, in the last decade due to experience acquired and the introduction of second-generation contrast agents, this technique has been re-evaluated as contrast-enhanced US (CEUS) allows detection and characterization of most focal lesions of the spleen with a high sensitivity and a good specificity. Gray-scale US presents a low specificity in splenic infarctions with a high rate of false negative cases, whereas specificity reaches 100 %, if the examination is performed using US contrast agents. Gray-scale US can provide a correct diagnosis in simple cysts, whereas CEUS is useful when cystic lymphangioma is suspected. In the study of splenic lesions, the most important problem is to differentiate between angioma, hamartoma, lymphoma, and metastasis. CEUS reaches a good specificity in the differentiation of benign from malignant splenic lesions, as hypo-enhancement in the parenchymal phase is predictive of malignancy in 87 % of cases. In conclusion, Gray-scale US and particularly CEUS are at present widely indicated in the study of focal splenic lesions.

Kaposi's sarcoma (KS) is an aggressive, multifocal oncologic disease, which frequently involves skin and internal organs, predominantly affecting homosexual men with AIDS. Hepatic KS is rarely reported in living patients, while autopsies show liver involvement in 35% of patients with KS. Ultrasound (US) of the liver in AIDS patients shows hyperechoic nodules with periportal bands; CT shows a hypodense lesion before and after contrast administration, but in the late phase after iodinated contrast agent injection the nodules are enhanced. Those findings are considered indicative of hepatic KS [1-3].

About 40% of the Italian HIV-1 epidemic due to non-B variants is sustained by F1 clade, which circulates at high prevalence in South America and Eastern Europe. Aim of this study was to define clade F1 origin, population dynamics and epidemiological networks through phylogenetic approaches. We analyzed pol sequences of 343 patients carrying F1 subtype stored in the ARCA database from 1998 to 2009. Citizenship of patients was as follows: 72.6% Italians, 9.3% South Americans and 7.3% Rumanians. Heterosexuals, Homo-bisexuals, Intravenous Drug Users accounted for 58.1%, 24.0% and 8.8% of patients, respectively. Phylogenetic analysis indicated that 70% of sequences clustered in 27 transmission networks. Two distinct groups were identified; the first clade, encompassing 56 sequences, included all Rumanian patients. The second group involved the remaining clusters and included 10 South American Homo-bisexuals in 9 distinct clusters. Heterosexual modality of infection was significantly associated with the probability to be detected in transmission networks. Heterosexuals were prevalent either among Italians (67.2%) or Rumanians (50%); by contrast, Homo-bisexuals accounted for 71.4% of South Americans. Among patients with resistant strains the proportion of clustering sequences was 57.1%, involving 14 clusters (51.8%). Resistance in clusters tended to be higher in South Americans (28.6%) compared to Italian (17.7%) and Rumanian patients (14.3%). A striking proportion of epidemiological networks could be identified in heterosexuals carrying F1 subtype residing in Italy. Italian Heterosexual males predominated within epidemiological clusters while foreign patients were mainly Heterosexual Rumanians, both males and females, and South American Homo-bisexuals. Tree topology suggested that F1 variant from South America gave rise to the Italian F1 epidemic through multiple introduction events. The contact tracing also revealed an unexpected burden of resistance in epidemiological clusters underlying the need of public interventions to limit the spread of non-B subtypes and transmitted drug resistance.

Amiodarone is a highly effective antiarrhythmic drug. Its long-term use may, however, lead to several adverse effects, with pulmonary toxicity being the most serious. The article presents the case of a 78-year-old woman with a history of cardiac surgery, who after 2 years of amiodarone therapy for prophylactic treatment of atrial fibrillation developed amiodarone pneumonitis mimicking an acute pulmonary edema. The patient failed to respond to diuretic therapy and several courses of anti-infective therapy. Differential diagnosis of different causes of pulmonary infiltrates did not demonstrate any other abnormality. Lung biopsy findings were consistent with the diagnosis of amiodarone pneumonitis. Given the widespread use of amiodarone as an antiarrhythmic agent, pneumologists and cardiologists should consider this important adverse effect as a differential diagnosis of pulmonary distress refractory to therapy in all patients treated with amiodarone who present with respiratory symptoms and pneumonia-like illness.

Introduction: Mediastinal syndrome is suspected on the basis of clinical symptoms and is generally confirmed by chest radiography or computed tomography (CT). However, also grey scale ultrasound (US) and contrast enhanced US (CEUS) are useful in this hematologic emergency as they provide the possibility to perform US-guided biopsy and histological diagnosis., Materials and Methods: 15 Patients affected by mediastinal syndrome were prospectively studied using B-mode US and CEUS; 13 of these patients, who had no other lesions, were proposed for US-guided biopsy of the mediastinal mass, but only in 12 patients biopsy was technically possible., Results: In this study, B-mode US reached an excellent sensitivity (100%) in evidencing the lesions but a low specificity which did not exceed 30-40%. CEUS reached an elevated specificity identifying neoplastic pathologies if both the early and the late phases are considered (90-86.6%). US-guided biopsy was possible in 92.3% of lesions showing a diagnostic adequacy of 91.66%., Conclusions: B-mode US associated with CEUS and US-guided biopsy reached an elevated accuracy in the diagnosis of mediastinal masses. If these results are confirmed by further studies, this diagnostic procedure could be included in the routine management of mediastinal syndrome.

Hepatic artery pseudoaneurysm is a rare complication of amebic or pyogenic liver abscesses, and it is generally diagnosed because of hemobilia due to rupture of the aneurysm into the biliary tract. The authors describe a case of vascular complication in a patient affected by amebic liver abscess. Pseudoaneurysm was diagnosed and resolved without hemobilia.

Introduction: The authors report their experience in 60 patients with infectious and neoplastic peripheral pulmonary lesions studied by conventional radiology, B-Mode ultrasound (US) and computed tomography (CT). In view of the particular pulmonary vascularization (consisting of both pulmonary and bronchial arteries) the patients underwent also contrast enhanced ultrasound (CEUS) using a II-generation contrast agent, SonoVue (sulphur hexafluoride microbubbles surrounded by a phospholipid shell)., Methods and Results: In this study, the sensitivity of CEUS reached 95% in the characterization of peripheral pulmonary lesions, which is similar to the sensitivity of CT (97%). The method used in this case-study was free of significant side effects., Discussion: This preliminary clinical experience seems to confirm the possibility of using SonoVue enhanced US to make a differential diagnosis between infectious and neoplastic lesions based on a qualitative and quantitative assessment, by evaluating the enhancement pattern (homogeneous or inhomogeneous), arrival time of the contrast agent in the lesion, the possibility to identify the pulmonary arteries and time of contrast agent elimination.

Introduction: In this survey we evaluated the usefulness of ultrasonography (US) in the diagnosis, and in the treatment of complicated hydatid cysts., Materials and Methods: From June 1985 to June 2004, 221 patients with 294 hydatid cysts were examined. Twenty patients (9.0%) presented 22 complicated cysts (7.4%): 9 with infection, 5 ruptured into the bile ducts, 2 bilomas, 2 cysto-pleural fistulas, 2 allergic reactions, 1 rupture into the peritoneum and 1 intrasplenic hematoma. In all cases, US yielded a specific or suspected diagnosis, also in complications affecting non-hepatic sites, confirmed by computed tomography (CT), endoscopic papillotomy or percutaneous US-guided sampling. All patients with complicated cystic echinococcosis were treated with Albendazole 800 mg/day for at least 3 months. In addition to this therapy, 12 underwent US-guided drainage (9 infected cysts, 2 bilomas, 2 cysto-pleural fistulas, 1 intrasplenic hematoma); of these patients 3 subsequently underwent surgery because US-guided treatment was ineffective. Five patients were treated with perendoscopic sphincterotomy for obstruction of the bile passages, while 3 patients received only medical therapy., Results: Medical, echoguided and surgical treatments led to resolution of the complications and complete remission of the parasitic pathology in 19/20 patients (95%) and in 21/22 cysts (95.4%). There was partial remission in 1 case only. The therapy did not cause major complications and the results were confirmed during follow-up lasting from 5 months to 15 years (mean time 3 years)., Discussion and Conclusion: This study shows that the incidence of complications of hydatid cysts is low and that correct echographic management allows a rapid diagnosis and optimization of treatment in most cases.

Liver transplantation is indicated in end-stage chronic viral liver disease, but unless adequate prophylaxis is administered, the patient will in most cases develop recurrent hepatitis B (HBV) and C (HCV) virus infection. Today, patients receiving prophylaxis using nucleoside analogue drugs with or without specific immune globulin drugs in connection with orthotopic liver transplantation for HBV related cirrhosis, present low risk of relapse and high 5-10 year survival rates. Lamivudine was the first drug used in the prophylactic treatment, but this drug has increasingly been combined with or replaced by adefovir due to the low genetic barrier, which causes viral resistance. Most patients develop viral recurrence after orthotopic liver transplantation for HCV related cirrhosis, and in an elevated number of cases, cirrhosis and hepatic insufficiency set in after a few years. Prophylaxis before transplantation and pre-emptive treatment using interferon and ribavirin present numerous side effects resulting in reduction of doses and suspension of therapy, with consequently low sustained virological remission rates and risk of rejection.The treatment is better tolerated by patients with histologically confirmed chronic disease, but also in these patients virological remission rates are low. This pathology requires new therapeutic protocols and/or new drugs in order to obtain better compliance and better responses.

Background & Aims: Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy with pegylated IFN-alpha-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated., Methods: One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-alpha-2b 1.5 microg/kg per week and ribavirin 1000-1200 mg/day for 48 weeks and followed up for 24 weeks., Results: By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low gamma-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6-79.6) and low viral load (OR, 3.8; 95% CI: 1.1-12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response (P = .2) or with early response (P = .3)., Conclusions: Retreatment with pegylated IFN-alpha-2b and ribavirin of multi-experienced and "difficult to treat" nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low gamma-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR.

Treating patients with HCV-associated thrombocytopenia is a problem, because the pathogenesis of thrombocytopenia is still unclear. We evaluated the clinical and haematological response to leucocyte interferon-alpha in 20 naive patients with chronic hepatitis C and thrombocytopenia (platelet count <140 x 10(9)/l for at least six months) without portal hypertension and/or hypersplenism. They were treated with leucocyte interferon-alpha (3 MU three times per week) for 12 months and followed up for 12 months. Biochemical (ALT) and virological (HCV-RNA) responses were determined. Two patients discontinued treatment because of hyperthyroidism. Of the 18 patients who completed treatment, 12 (66%) showed a biochemical response, 10 of whom (55.5%) also showed a virological response. At the end of follow-up, four patients (22%) showed a complete (biochemical and virological) response. During treatment, platelet counts decreased to less than 10-20% of pretreatment values in most patients. Three of the four patients with a complete response showed a platelet increase during treatment and throughout the follow-up period. In HCV-associated thrombocytopenia leucocyte interferon-alpha is well tolerated and in cases of sustained virological inhibition is able to ameliorate the disease by increasing the platelet count.

An analysis of the epidemiology of non-parasitic hepatic cysts (NPHCs) has been carried out comparing these data with those of the current literature. This sample shows an incidence of 4.65%, which is greater than those reported by other authors. No difference between the two sexes was seen, but a very high incidence above 40 years of age was found.