Mitochondrial DNA: a proinflammatory 'enemy from within' during HIV infection?

Mitochondria are crucial in cell life, as they are the main intracellular source of energy, and have a main role in cell death as they contain molecules able to trigger apoptosis. However, mitochondria can also release molecules called ‘damage-associated molecular patterns’ (DAMPs) that trigger a potent innate immune response and cause inflammation through the engagement of the Toll-like receptors (TLR). During human immunodeficiency virus (HIV) infection, a proinflammatory status is present that is not completely explained by the activity of the virus per se, or by the effective immune response against the virus. However, the presence of significant amounts of DAMPs of mitochondrial origin, such as extracellular plasmatic mtDNA, in the peripheral blood of subjects with HIV infection suggests that part of the inflammation typical of such infection could be because of the activity of these molecules, and thus opens new therapeutic perspectives

Successful treatment of BK virus associated-nephropathy in a human immunodeficiency virus-positive kidney transplant recipient

BK virus (BKV) is an opportunistic pathogen in those with impaired immunity. Viral replication is generally asymptomatic but is able to induce cytopathic alterations in renal cells. If BKV infection is left untreated, it leads to BKV-associated nephropathy (BKVAN) and graft loss. There is scarce experience in the management of BKV infection in kidney transplant recipients living with HIV. We report the successful treatment of BKVAN in an HIV-positive kidney transplant recipient who experienced BKV replication in the immediate post-transplantation period. A change in therapy from calcineurin inhibitor to sirolimus, steroid withdrawal and a short course of an immunomodulatory agent (leflunomide) controlled BKV viremia in the absence of drug side-effects or impairment of graft function

Never Give Up: lesson learned from a severe COVID-19 patient.

We here report the clinical course of a 72-year old Caucasian male (M.A.) admitted for SARS-CoV2 pneumonia at our University Hospital in Modena. A multidisciplinary medical staff composed by different specialists (infectious diseases, pulmonology, intensive care) was in charge for caring and assuming shared clinical decisions

Optimization strategies for HIV, syphilis and hepatitis testings in infectious disease and dermatology clinics: preliminary results of Modena collaboration experience

Background: HIV and sexually transmitted diseases (STDs) screening tests are usually offered in many Italian health institutions. These tests are very important for detection of HIV and STDs, for treating them at an early stage and for prevention of diffusion inside communities. Generally, HIV test is the only screening exam performed in Infectious Disease Clinic (IDC). Increased collaboration between IDC and STDs Centre using the same approach to test sexually transmitted infections could implement the number of new diagnoses. In the Azienda Ospedaliero-Universitaria (AOU) of Modena, the IDC and STDs Centre of Dermatology Clinic began a strict collaboration and adopted a common diagnostic profile including HIV, syphilis, HBV and HCV screening tests since 2013. The aim of the study was to observe the results of a seven-years collaboration in term of number of new HIV and STDs diagnoses. Material & Methods: Consecutive patients who underwent at least 1 screening test for HIV, syphilis, HBV and HCV from January 2010 to September 2016 in IDC or STDs Centre were included. Demographical data were electronically recorded in clinical databases. “Linkage to care” was obtained through a capture and recapture method using Modena HIV surveillance System and Modena HIV clinic databases. Results: During the study period 10675 admittances related to 8623 patients, who carried out at least 1 screening test, were registered in the centres. They were mainly male (68.2%). Median age was 33 years-old (IQR 26-43). Foreigners represented 26.5% of tested people. Since 2013 an increasing number of admittances was observed (1343 accesses in 2010 and 1901 in 2015). HBV, HCV and syphilis tests increased in IDC after 2013 as well as HIV tests in STDs Centre (Figure 1). A total of 700 people were positive for at least 1 screening test: 71 with HIV infection (2016 incidence rate 1.4%), 314 with syphilis (2016 incidence rate 1.3%), 182 with HCV infection (2016 incidence rate 1.64%) and 161 with HBV infection (2016 incidence rate 3.8%). The number of HIV and HBV positive tests increased in the last 2 years but the trend was statistically significant only for HIV (p<0.001). 57% of HIV new infections were observed in Italian men, while 82% of new HBV infections were detected in young foreigners. During the study period the number of new syphilis infections showed a reduction (p<0.001) while HCV positive tests were changeless (p=0.245). 87.6% of new infections were found be linked in care in AOU of Modena. Conclusion: The agreement between IDC and STDs Centre has proven to work well increasing the diagnosis over the time and obtaining a good results in “linkage to care”, which allows to patients with positive screening test to be sent to the pertinent Clinic for further investigations and therapeutical management

Optimization strategies for HIV, hepatitis and syphilis testing in Infectious Disease Clinic and Dermatology Unit of Modena: seven-years results of collaboration experience

Introduction: Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis infections modify the epidemiology and presentation of each other. Screening tests are very important for detection of sexually transmitted infections (STIs), for treating them at an early stage and prevent the diffusion inside communities. “Test & Counselling” Ambulatory of Infectious Disease Clinic (T&C-IDC) and Sexually Transmitted Diseases Ambulatory of Dermatology Unit (STDs-DU) of the Azienda Ospedaliero-Universitaria Policlinico of Modena began collaboration in 2010 and adopted a common diagnostic profile since 2013. The main objective was to analyse the results of screening tests performed in the T&C-IDC and STDs-DU during the study period in order to identify early HIV, HBV, HCV and syphilis infections. The secondary objective was to evaluate the efficacy of our collaboration in term of number of new STIs diagnoses and linkage to care. Material and Methods: Consecutive patients referred to the T&C-IDC and STDs-DU from January 2010 to December 2016, with at least one performed screening test for HIV, HBV, HCV and syphilis were enrolled. Demographic and laboratory data were acquired from each patient. Linkage to care of positive patients was obtained through a join of different outpatient clinical databases. Results: During the seven-years observation we collected 13117 admittances for 9154 patients. Median age was 35.1 years ± 12.6 and foreign-born population represents 29% of the tested people. People who resulted positive for at least one screening test increased during the study period. A total of 668 infections were detected in 644 patients. Discussion: The agreement between T&C-IDC and STDs-DU has proven to work well increasing the diagnosis over the time and obtaining a good results in linkage to care, which allows to patients with positive screening test to be sent to the pertinent Clinic for further investigations and therapeutic management

Construct validation of a Frailty Index, an HIV Index and a Protective Index from a clinical HIV database

Standard care for HIV clinical practice has started focusing on age-related problems, but despite this recent change physicians involved in HIV care do not often screen HIV patients for frailty. Our aim was to construct three indexes from an HIV clinical database (i.e. Frailty Index, (FI), HIV Index, (HIVI), and Protective Index (PI)) and to assess levels of frailty, HIV severity and demographic and protective lifestyle factors among HIV patients. Methods and findings We included data from 1612 patients who attended an Italian HIV clinic between September 2016 and December2017 (mean\ub1SD age: 53.1\ub18 years, 73.9% men).We used 92 routine variables collected by physicians and other health care professionals to construct three indexes: A 72-item FI (biometric, psychiatric, blood test, daily life activities, geriatric syndromes and nutrition data), a 10-item HIVI (immunological, viral and therapeutics) and a 10-item PI (income, education, social engagement, and lifestyle habits data)(the lower the FI and HIVI scores, and the higher the PI scores, the lower the risk for participants).The FI, HIVI and PI scores were 0.19\ub10.08, 0.48\ub10.17 and 0.62\ub10.13, respectively. Men had higher FI (0.19\ub10.08 vs 0.18\ub10.08; p = 0.010) and lower HIVI (0.47\ub10.18 vs 0.50\ub10.15; p = 0.038) scores than women. FI and HIVI scores both increased 1.9% per year of age (p < 0.001), whereas the PI decreased 0.2% per year (p<0.050). In addition, the FI score increased 1.6% and the PI score decreased 0.5% per year of HIV infection (p < 0.001). Conclusion It is feasible to assess levels of frailty, HIV severity and protective lifestyle factors in HIV patients using data from a clinical database. Frailty levels are high among HIV patients and even higher among older patients and those with a long duration of HIV. Future studies need to examine the ability of the three indices to predict adverse health outcomes such as hospitalization and mortality

Collaboration experience between Dermatology Unit and Infectious Disease Clinic in Modena: optimization strategies for HIV, hepatitis and syphilis screening tests

Introduction Screening tests for HIV, HBV, HCV and syphilis are very important to detect and treat these infections at an early stage and prevent their diffusion inside communities. Sexually Transmitted Diseases Ambulatory of Dermatology Unit (STDs-DU) and “Test & Counselling” Ambulatory of Infectious Disease Clinic (T&C-IDC) in Modena began collaboration in 2010 and adopted a common diagnostic serological profile since 2013. Objective The main aim of the study was to analyse the results of screening tests performed in the STDs-DU and T&C-IDC, comparing the results obtained after the adoption of the shared protocol with the previous period. The secondary objective was to evaluate the efficacy of our collaboration in term of number of new diagnoses and linkage to care. Materials and Methods Consecutive patients referred to the STDs-DU and T&C-IDC from January 2010 to December 2016, with at least one performed screening test for HIV, HBV, HCV and syphilis were enrolled. Referral of patients with a new infection was obtained by capture-recapture methods in hospital databases. Results During the seven-years observation we collected 13117 admittances for 9154 patients. We observed a significant increase in the number of screening tests (p<0.001) and ratio between tests and admissions (p=0.002). 644 (7.0%) people with at least one infection were diagnosed. Among these, the most common was syphilis (41.9%), followed by HBV (25.7%), HCV (21.4%) and HIV (10.9%). Syphilis and HCV occurred predominantly in Italians (72.5% and 81.1%) and males (75.7% and 75.5%), while foreign-born (85.5%) mainly harboured HBV infection. HIV diagnosis was detected more frequently among males (67.1%) with a similar proportion between Italians and foreign-born. 543 out of 644 (84.3%) patients were linked to care. Conclusions The cooperation between STDs-DU and T&C-IDC has proven to work well increasing the diagnosis over the time and obtaining good results in linkage to care

Acinetobacter baumannii Resistance to Sulbactam/Durlobactam: A Systematic Review

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have limited therapeutic options. Sulbactam-durlobactam is a combination of two beta lactamase inhibitors with activity against CRAB under phase 3 clinical investigation. We performed a systematic review on in vitro studies reporting A. baumannii resistances against sulbactam/durlobactam. We considered "resistant" species to be those with MIC >= 8 mg/L. Ten studies were included in the review (9754 tested isolates). Overall, 2.3% of A. baumannii were resistant to sulbactam/durlobactam, and this percentage rose to 3.4% among CRAB subgroups and to 3.7% among colistin-resistant strains. Resistance was 100% among metallo beta-lactamase-producing strains. Overall, in 12.5% of cases, sulbactam/durlobactam resistance was associated with the production of NDM-1, in 31.7% of cases with the substitutions in the PBP3 determinants, and in the remaining cases the resistance mechanism was unknown. In conclusion, A. baumannii resistance towards sulbactam/durlobactam is limited, except for MBL-producing strains