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In July 23, the World Health Organization (WHO) declared monkeypox (MPX) a global health emergency of international concern given its rapid spread. So far, most current MPX outbreaks have involved young men who have sex with men (MSM), although with overall mild, self-limiting clinical manifestations. We aim to describe the case of an HIV positive young MSM whose status of immune compromission probably contributed to a more severe clinical course of MPX disease, thus requiring hospitalization and antiviral treatment. He was effectively treated with Cidofovir that may be considered as a valuable component of a multi-faceted management of severe MPX.

On July 23, the World Health Organization (WHO) declared monkeypox (MPX) a global health emergency of international concern given its rapid spreading. So far, most current MPX outbreaks have involved young men who have sex with men (MSM), although with overall mild, self-limiting clinical manifestations. We aim to describe the case of a young MSM, HIV positive, whose status of utter immune suppression probably contributed to worsen the clinical course of MPX disease, thus requiring hospitalization and antiviral treatment. He was effectively treated with Cidofovir that may be a valuable component of a multi-faceted management of severe MPX.

The continuum of control plays a crucial role in the marking of transitivity in Latin, witnessed also by the alternation between the personal and impersonal encoding of eventualities. The present study investigates argument marking with some ‘impersonal’ verbs. These patterns reflect the crystallisation of a seemingly widespread construction in the early stages of the language, probably of Indo-European inheritance, the use of the third-person singular active with an accusative/oblique argument to denote the spontaneous manifestation of an eventuality and the lack of control of the A/S argument, a pattern competing with the passive form for some verbs in this domain. These impersonal constructions in Latin point to the existence of a dependent-marked, agentive-coding subsystem, similar to analogous constructions in languages with semantic alignment. This evidence suggests that Latin is a language with a syntactically based (nominative–accusative) and (dependent-marked) semantically based subsystems of alignment, sensitive to the notion of control.

The chapter examines the syntactic behaviour of a special class of non-canonical subjects, namely nominal infinitives, in Latin and in one of its daughter languages, Old Italian. The data show that Latin infinitives can appear in subject function only if the finite verb of the clause belongs to a restricted set of unaccusative predicates, corresponding to states or telic changes of state. In other words, Latin infinitives cannot surface as subjects of unergative and transitive predicates, thus conforming to a widespread cross-linguistic trend concerning non-canonical subjects. Vice versa, the distribution of subject infinitives in Old Italian is unrestricted, insofar as they are eligible to subjecthood regardless of the finite verb of the clause. The hypothesis this chapter explores is that the change which took place from Latin to Old Italian, involving the syntactic status of nominal infinitives, might have started from the clauses with a finite experiencer predicate.

Background. The mortality rate for coronavirus disease-19 (COVID-19) increases with age. Some anti-inflammatory drugs such as tocilizumab or steroids have been proposed for the treatment of severe disease; however, few data are available in the elderly. Methods. A retrospective case-series of patients hospitalized between March 1st and June 15th, 2020 with confirmed COVID-19 by RT-PCR testing on throat/nasopharyngeal swabs and age ≥ 65 years was analysed. Patients were retrospectively divided into three groups according to the chosen treatment [standard of care (SOC), tocilizumab or corticosteroids] and patient characteristics and occurrence of adverse events were compared among groups. Results. Overall, 206 patients were included, 148 treated with standard of care, 42 with steroids and 16 with tocilizumab. Patients treated with steroids or Tocilizumab presented more frequently with fever (p = .003), dyspnea (p < .001), bilateral opacities/infiltrates at chest X-ray (p =.026) or CT-scan (p = .020), and more frequently required non-invasive/invasive ventilation (p < .001). Crude mortality was 27%, without differences among groups (p = .074). No specific adverse events were observed during/after the administration of steroids or tocilizumab; however, a trend towards an increased risk of secondary infections was described compared to SOC (p = .097). At multivariate logistic regression, only tocilizumab administration was an independent predictor of secondary infections (aOR = 6.72, 95% CI = 1.43-31.39, p = .015). Conclusions. Tocilizumab and corticosteroid could have a possible role for severe form of pneumonia in course of COVID-19 also in elderly patients, even if great attention to the monitoring of infectious complications should be paid in this special population.

The latest developments in precision medicine allow the modulation of therapeutic approaches in different pathologies on the basis of the specific molecular characterization of the patient. This review of the literature coupled with in silico analysis was to provide a selected screening of interactions between single-nucleotide polymorphisms (SNPs) and drugs (repurposed, investigational, and biological agents) showing efficacy and toxicityin counteracting Covid-19 infection. In silico analysis of genetic variants related to each drug was performed on such databases as PharmGKB, Ensembl Genome Browser, www.drugs.com, and SNPedia, with an extensive literature review of papers (to May 10, 2020) on Covid-19 treatments using Medline, Embase, International Pharmaceutical Abstracts, PharmGKB, and Google Scholar. The clinical relevance of SNPs, known as both drug targets and markers, considering genetic variations with known drug responses, and the therapeutic consequences are discussed. In the context of clinical treatment of Covid-19, including infection prevention, control measures, and supportive care, this review highlights the importance of a personalized approach in the final selection of therapy, which is probably essential in the management of the Covid-19 pandemic.

The HIV V2179-181 (HXB2 numbering) tripeptide mediates binding to α4β7 integrin, which is responsible for GALT homing. Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features. Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated. At multivariate analysis, lower V2 length and higher NC correlated with low CD4 cells; no association was found with PNGs. A greater variability pertained positions 162-163, 164-167, 169, 175-179, 187, 194 and 195 in B sequences, and 163 and 177 in X4 tropic viruses. LDV was the most common tripeptide. Asp180 was highly conserved; Leu179 was more frequently observed in non-B and in recent infections compared to others, while Val181 was found in recent infections and in MSM. Further studies to deeply explore the clinical significance of these associations are warranted.

Background The spectrum of clinical manifestations of CoronaVirus Disease-19 (COVID-19) is not yet completely known. In elderly, mortality and extra-pulmonary involvement appear to be more frequent than expected. Methods A multicentric-retrospective-case-series of patients hospitalized between March 1st and June 15th, 2020 with confirmed COVID-19 by RT-PCR testing on throat/nasopharyngeal swabs and age ≥65 years was analysed. Based on the “Clinical Frailty Scale” (CFS), patients were classified into three groups according to the resulting score: 1-3 (group A), 4-6 (group B), 7-9 (group C). Results Overall, 206 patients were included. Crude mortality was 27%. According to CFS, on admission, 60 patients (29%) were assigned to group A, 60 (29%) to group B, and 86 (42%) to group C. The following features were significantly more frequent among group C patients in comparison with groups B and A: mental confusion (65% vs 33% vs 7%, respectively, p

Highlights • In elderly COVID-19 inpatients, admission NEWS2 scores did not predict mortality. • Of components of NEW2 score, only systolic blood pressure predicted mortality. • A high variability in NEW2 score predicted mortality. • NEWS2 score does not consider the degree of supplemental oxygen patients require. • A more sensitive early warning score for COVID-19 is needed.

Despite respiratory symptoms are typically found during the course of coronavirus disease 2019 (COVID‐19), gastrointestinal manifestations are increasingly described. However, data regarding COVID‐19‐associated pancreatic injury are still limited, as well as the mechanisms underlying COVID‐19 induced‐pancreatic damage have not been completely clarified. Herein, we described pancreatic abnormalities in six (8.5%) out of 70 patients with COVID‐19 hospitalized in our unit from February 25, 2020 to May 10, 2020. We hypothesized that pancreatic damage may be associated with several factors including direct effect of SARS‐CoV‐2, inflammatory cascade, dehydration and multiple organ dysfunction.This article is protected by copyright. All rights reserved.

Objectives Fostemsavir, a novel attachment inhibitor targeting the HIV-1 gp120, has demonstrated wide in vitro activity. However, the high rate of HIV gp120 substitutions could jeopardize its efficacy. We investigated envelope (env) substitutions at positions associated with resistance to fostemsavir in patients with a new HIV-1 diagnosis according to HIV subtype and tropism. Methods Gp120 sequences from 409 subjects were retrospectively analysed and the presence of the L116P, A204D, S375H/M/T, M426L, M434I and M475I mutations was evaluated. Other amino acid changes at the same positions were also recorded. The variability at each amino acid position was evaluated using Shannon entropy. Results The frequency of mutations was: S375T (13.2%); M426L (6.8%); M434I (2.9%); M475I (2.7%); S375H (1.0%)/M (0.8%) and L116P (0.31%). Statistically significant differences were found at positions 375 (R5/non-R5 strains and B/non-B subtypes) and 426 (B/non-B subtypes); post hoc analysis revealed that significance for position 375 was steered by S375T while for position 426 significance was governed by unusual substitutions, in particular M426R (B/non-B, P Conclusions In conclusion, gp120 substitutions were detected in different subtypes and in both R5 and non-R5 variants. Despite the great variability of gp120, the frequency of mutations was low overall and the predominant substitution was S375T, the role of which in reducing fostemsavir efficacy is less substantial.

Background Direct-acting antiviral (DAA)-based treatment of hepatitis C virus (HCV) has been associated with high sustained virological response (SVR) rates and good tolerability in randomized clinical trials. This study was performed to assess the safety and effectiveness of DAAs in both HCV mono-infected and HIV/HCV co-infected patients. Methods All consecutive HCV-infected patients, including HIV/HCV co-infected patients, receiving DAA-based treatment from February 2015 to September 2016 at the study clinic were included. Clinical, virological, and biochemical data were retrieved. The primary end-point was the SVR12 (HCV RNA undetectable 12 weeks after the end of treatment) is commonly used worldwide. The secondary end-point was the safety profile of DAAs during the treatment period. Results A total of 382 patients were included; 62 were HIV/HCV co-infected. Cirrhosis was found in 256 patients (67.4%). SVR12 was achieved in 365/382 (95.5%) individuals (58/62 HIV/HCV co-infected, 93.5%) in the intention-to-treat (ITT) analysis. A platelet count 9 /l (odds ratio (OR) 4.12, 95% confidence interval (CI) 1.5–11.3, p =0.006), HCV genotype 3 infection (OR 5.49, 95% CI 1.9–15.7, p =0.002), liver stiffness >20kPa (OR 3.05, 95% CI 1.03–8.96, p =0.04), and Model for End-Stage Liver Disease (MELD) score >10 (OR 5.27, 95% CI 1.16–23.8, p =0.03) were associated with lower SVR rates. On multivariate analysis, only genotype 3 infection remained a negative predictor of SVR (OR 21.6, 95% CI 3.81–123, p =0.001). Treatment discontinuation was observed in 10 subjects. Severe adverse events (SAEs) occurred in 17 patients (4.5%). Conclusions High SVR12 rates were observed in both HCV mono-infected and HIV/HCV co-infected individuals. Overall, DAA-based treatment was safe and there were no differences in terms of SAEs and treatment discontinuation between the two groups.

Background Direct antiviral agents (DAAs) for chronic hepatitis C showed great effectiveness and good safety profile. So far, few data are available about their use in elderly subjects. Aim To assess management, safety and outcome of DAAs treatments in the elderly. Methods This retrospective, single-centre study enrolled all patients aged ≥65 years, compared by age (group A: 65–74 years, group B: ≥75 years), who completed DAAs between February 2015–November 2016. Variables potentially associated to adverse events (AEs) were analyzed. Sustained virological response (SVR) was evaluated at 12-weeks follow-up. Results DAAs were administered to 221 patients aged ≥65 years (males: 112; group A: 130, group B: 91). Prescribed regimens were: sofosbuvir-based: 44 patients (19.9%), simeprevir-based: 25 (15%), ledipasvir-based: 49 (22.2%), daclatasvir-based: 12 (5.4%), paritaprevir/ritonavir + ombitasvir ± dasabuvir: 91 (41.2%). Ribavirin was used in 121 patients. In 58 subjects co-medications were adjusted due to drug interactions. At least one AE occurred in 130 patients, including 13 SAEs, mainly in older subjects (p = 0.04). Female sex (p = 0.04), liver stiffness (p = 0.023), use of simeprevir (p = 0.03) and ribavirin (p = 0.009) were associated with AEs. SVR-12 was achieved in 96,9% of subjects. Conclusions A careful baseline evaluation and a strict monitoring allow to optimise management and outcome of DAAs in elderly.

Background The association between X4 virus and an increased risk of non-AIDS-events has been reported. Morbidity/mortality due to non-AIDS events, which are properly predicted by the CD4/CD8 ratio and VACS index, have become particularly remarkable in HIV-infected patients receiving effective combined antiretroviral therapy (cART). Methods We verified the validity of the syllogism: as HIV-tropism (CRT) contributes to the onset of non-AIDS events which are successfully predicted by the CD4/CD8 ratio and VACS index, then CRT correlates with these two variables. The CD4/CD8 ratio and VACS index at baseline and overtime were analyzed according to CRT tested before the first successful cART regimen in newly-diagnosed patients. Results Patients with R5 variants had a significantly lower baseline VACS percentage risk [mean (95%CI):18.2%(16.1-20.3) vs 24.3%(18.2-22.5), p = 0.002] and higher baseline CD4/CD8 ratio [mean (95%CI):0.43 (0.38-0.47) vs 0.28 (0.19-0.36), p = 0.002] than non-R5 patients. After an initial drop, VACS increased again in R5 and non-R5 patients and the two trend curves almost overlapped. The CD4/CD8 ratio had an increasing trend in both R5 and non-R5 patients; however, even though non-R5 patients had a greater gain of CD4+, they maintained a lower CD4/CD8 ratio at any time point. Conclusion Our study confirms an association between pre-therapy CRT, CD4/CD8 ratio and VACS. A successful cART regimen positively affects the CD4/CD8 ratio; however, the disadvantage conferred by a non-R5 CRT is maintained overtime. The restoration of VACS in all patients could be directly due to variables included in the VACS calculation and to factors that adversely influence these variables.

This review outlines the association between tuberculosis and diabetes, focusing on epidemiology, physiopathology, clinical aspects, diagnosis and treatment, and evaluates future perspectives, with particular attention to developing countries.

We aimed to evaluate HIV-1 compartmentalization between the cerebrospinal fluid (CSF) and plasma and investigate as to which extent HIV-1 strains in CSF differ from those in blood and whether a correlation with either plasma viral load (pVL) or an altered blood-brain barrier (BBB) does exist.We retrospectively evaluated paired CSF/blood samples collected from 86 HIV+ patients. HIV-RNA quantification, pol (PR/RT), and V3 sequencing were performed. HIV coreceptor tropism (CRT) was inferred (g2p, false-positive rate 10%, FPR). Data of standard CSF analysis were also reviewed; an altered CSF/plasma albumin ratio signified BBB damage. Neurological abnormalities (NA) were recorded.Overall, 32% of patients had a CSF/plasma HIV-RNA ratio 1 (discordance); 3% of patients had detectable CSF HIV-RNA despite suppressed pVL (escape). Discordance was more frequent in ART-treated patients (p 0.001) and in patients with NA (p = 0.016), but was independent of BBB damage (p = 0.65) and AIDS diagnosis (p = 0.96). Finally, CSF/plasma discordance was significantly more frequent (p 0.0001) in patients with lower pVL values ( 10.000 copies/ml). Env divergence 10% was found in 44% of sequences and was associated with ART (p = 0.008) and NA (p = 0.037). Overall, 24% of patients had a discordant CSF/blood CRT. A 100% nucleotide identity was observed in only 7.3% of pol sequences; notably, 10% of patients had resistance-associated mutations in CSF, but not in blood.Our data confirm an independent replication and evolution of HIV within the CSF. A number of factors either hinder or contribute to the compartmentalization of HIV.

We aimed to investigate to what extent a first-line DTG-based ART regimen reduces HIV-RNA in semen compared to plasma.In this prospective, observational study, ART-naïve, HIV-infected males starting their first ART regimen with DTG plus TDF/FTC or ABC/3TC were enrolled. Paired blood (BP) and seminal plasma (SP) samples were collected at baseline (T0) and at week-2/4/12/24 after ART initiation. Sexually transmitted infections (STI) were ruled out before enrolment.Median baseline HIV-RNA levels were lower in SP compared to BP (657 versus 38.200 copies/ml, p 0.001), three subjects had undetectable semen HIV-RNA. After 12 weeks of treatment, HIV-RNA was below the quantification limit in both BP and SP of 11 pts (61.1%). Discordant results were obtained in 6 subjects (33.3%), showing quantifiable HIV-RNA in blood only (2 cases) and in semen only (4 cases). Finally, one subject had a positive HIV-RNA in SP/BP. At W24, only in 2/16 subjects (12.5%) HIV-RNA was detectable in semen, while in the others it was negative on SP/BP. No concurrent STI was found in subjects with detectable VL in semen.DTG demonstrated effectiveness in reducing VL with different kinetics in blood and semen, despite seminal viral suppression after 6 months of ART was not obtained in the totality of subjects.

Background Imported cases of multidrug resistant Plasmodium falciparum and treatment failure with artemisinin-based regimens, although rare, have been described also in Western countries and their management is often challenging. This is also due to an inadequate knowledge and implementation of health prevention measures. Case report A complex case of imported malaria caused by Plasmodium vivax/P. falciparum isolates in a patient who was not taking chemoprophylaxis while he was travelling in Cambodia is reported in this article. After failures of artemisinin-based and both oral and intravenous quinine-based regimens, a multidrug resistant P. falciparum was detected. The patient was successfully treated with atovaquone–proguanil. Conclusions This experience highlights the importance of a careful management that should be based not only on the most up-to-date guidelines, but also on the awareness of a rapidly evolving scenario.

Dengue fever (DF), an arbovirosis caused by Dengue viruses (DV, serotypes 1-4), is responsible for an increasing number of travel-related acute febrile illnesses due to population growth, climate changes, spreading by viremic travellers, and improved laboratory diagnosis. The presence of efficient vectors (mosquito Aedes albopictus) has also been described in temperate regions including Italy which is considered the most heavily infected European country. Normally characterized by non-specific signs and symptoms, DF incidence is probably underestimated, especially in non-endemic countries, but the risk of severe forms is substantial. Between August and November 2013, five DF patients (4 males, age 23-38) were observed in the Infectious Disease Clinic (University of Bari, Southern Italy). All had just returned from DF endemic areas (2 French Polynesia, 3 Dominican Republic); 4/5 were hospitalized. Common clinical features included acute febrile syndrome, headache (2 with retro-orbital pain), rash (all patients), two with bleeding manifestations and one with gum bleeding. Laboratory tests demonstrated leukopenia (4 patients), elevated liver enzymes (3 patients), and thrombocytopenia (1 patient). Serum samples for DV antibodies and RNA detection were analyzed by the Regional Arbovirosis Reference Laboratory. Viral RNA was identified in 2/5 patients (DV-4) and seroconversion in the remaining cases. All patients made a complete recovery. Recent literature was reviewed, focusing on epidemiology and vector distribution (especially European and Italian territories), pathogenesis, clinical features, diagnosis, and treatment including vaccine strategies. The occurrence of 5 DF cases during the period of highest vector activity (June-November) in Italy emphasizes the risk of local outbreaks in temperate regions. This paper highlights the importance of clinical alert for dengue also in non-endemic countries.

Background Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D’Amico might provide new insights on timing for antiviral therapy. Methods We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n = 575) or cirrhosis (n = 2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines. Results The SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients. Conclusion Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3–5) who are at greatest risk and have the most to gain from therapy.

The combination of sofosbuvir and simeprevir ± ribavirin (SOF + SMV ± RBV) for hepatitis C virus (HCV) treatment has been associated with high rates of sustained virological response (SVR). Few data are available regarding this regimen in HIV/HCV co-infected patients. This study evaluated the effectiveness and safety of a 12-week course of SOF + SMV ± RBV in a cohort of HCV monoinfected and HIV/HCV co-infected individuals. HCV-infected patients, with or without HIV infection, receiving a 12-week course of SOF + SMV ± RBV in four Italian centres from February to October 2015, were included in this retrospective observational study. Clinical and biochemical data were retrieved for all patients. A total of 88 individuals were evaluated: 29 (33.0%) HIV/HCV co-infected and 59 (67.0%) monoinfected. Most patients were males with HCV genotype 1b (62.5%) and 1a (25%) infection. RBV was used in 41 HCV monoinfected and 6 HIV/HCV co-infected patients. Cirrhosis was found in 67 patients (76.1%). The most common adverse events (AEs) were rash and/or pruritus (23.9%), fatigue (13.6%) and anaemia (9.1%). Serious AEs occurred in three patients (3.4%). No treatment discontinuations were observed. RBV use was associated with multiple AEs (P = 0.02). An overall SVR12 of 93.2% was achieved; 96.6% in HCV monoinfected and 86.2% in HIV/HCV co-infected individuals, without significance both in univariate (P = 0.09) and multivariate analyses (P = 0.12). A baseline platelet count ≥90 000/mm3 was associated with higher rates of SVR (P = 0.005). A 12-week course of SOF + SMV ± RBV was associated with good safety and high SVR12 rate both in HCV monoinfected and HIV-HCV co-infected individuals.

Introduction: Data regarding the association between diabetes mellitus (DM) and tuberculosis (TB) in Africa are scarce. DM screening among TB patients in Mozambique was carried out. Methods: The study was implemented from January to August 2016 in three Urban Health Centers in Beira, Mozambique and recruited adult (>18 years) patients newly diagnosed with pulmonary TB. Results: Three hundred and one patients were enrolled (67.4%, males mean age 31.7(SD 11 years). Diabetes was diagnosed in only 3 patients (1%) and impaired glucose tolerance (IGT) in an additional 6 subjects (2%). Conclusion: A lower than expected prevalence of DM was observed, which could be explained by the lack of traditional risk factors for DM (overweight, age over 45 years, hypertension and smoking) in Mozambique. Keywords: Diabetes mellitus, pulmonary tuberculosis, Beira, Mozambique

Marathi-Konkani varieties exhibit a series of verbal formations that derive from the univerbation of a participle plus a form of ‘be’. In the creation of these new, resynthesised, sections of the verbal paradigm, several instances of systematic homonymies arose, which recurrently involve the cells of the first and second person plural and affect several dimensions of the paradigm (aspect syncretism, mood syncretism and gender-agreement syncretism are all observed). At the same time, in inherited synthetic verb forms, the first and second person plural cells show neutralisation of inflection-class distinctions. According to the analysis proposed here, these homonymies can be exhaustively explained neither in terms of phonological development, nor with reference to the characteristics of morphosyntactic properties, but are at least in part due to a general tendency to “morphological equilibrium” that disfavours non-syncretic cumulative exponents uniquely associated with critically rare paradigm-cells.