Clostridium difficile infection has emerged as a major health problem. Because it is a spore-forming microorganism, C. difficile is difficult to eradicate and recurrences of the infection are ...frequent. The strong association of CDI with prior use of antibiotics led to the recognition that disturbances in the gut microbiota apparently plays a central role in CDI. Except for antibiotics, several other risk factors for CDI have been recognised, such as advanced age and use of proton pump inhibitors. The common characteristic of these factors is that they are associated with changes in the composition of gut microbiota. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with reduced microbiota diversity. C. difficile infection per se seems to be associated with changes in the representation of specific microbial populations (e.g. taxa) which either may act protectively against C. difficile colonization of the gut or may increase susceptibility for C. difficile infection. Therapeutic gut microbiota manipulation can be achieved by faecal microbiota transplantation, which is highly effective for the treatment of CDI.
•C. difficile colonization is characterized by decreased gut microbiota diversity.•C. difficile infection by might be driven by the presence of certain microbial taxa.•Faecal microbiota transplantation is the most effective therapy for CDI.
The COVID-19 pandemic has been a global medical emergency with a significant socio-economic impact. People with HIV (PWH), due to the underlying immunosuppression and the particularities of HIV ...stigma, are considered a vulnerable population at high risk. In this review, we report what is currently known in the available literature with regards to the clinical implications of the overlap of the two epidemics. PWH share the same risk factors for severe COVID-19 as the general population (age, comorbidities), but virological and immunological status also plays an important role. Clinical presentation does not differ significantly, but there are some opportunistic infections that can mimic or co-exist with COVID-19. PWH should be prime candidates for preventative COVID-19 treatments when they are available, but in the setting of resistant strains, this might be not easy. When considering small-molecule medications, physicians need to always remember to address potential interactions with ART, and when considering immunosuppressants, they need to be aware of potential risks for opportunistic infections. COVID-19 shares similarities with HIV in how the public perceives patients-with fear of the unknown and prejudice. There are opportunities for HIV treatment hidden in COVID-19 research with the leaps gained in both monoclonal antibody and vaccine development.
The success of combined antiretroviral therapy (cART) has led to a dramatic improvement in the life expectancy of people living with HIV (PLWH). However, there has been an observed increase in ...cardiometabolic, bone, renal, hepatic, and neurocognitive manifestations, as well as neoplasms, known as serious non-AIDS events/SNAEs, compared to the general population of corresponding age. This increase is linked to a harmful phenomenon called inflammaging/immunosenescence, which is driven by chronic immune activation and intestinal bacterial translocation. In this study, we examined immunological and metabolic parameters in individuals receiving current cART.
The study was conducted at Laiko General Hospital in Athens, Greece. Plasma concentrations of sCD14, IL-6, SuPAR, I-FABP, and LBP were measured in virally suppressed PLWH under cART with at least 350 CD4 lymphocytes/μL. We compared these levels between PLWH receiving integrase strand transfer inhibitors (INSTIs) and protease inhibitors (PIs) and attempted to correlate them with chronic immune activation and metabolic parameters.
Data from 28 PLWH were analyzed, with a mean age of 52 and 93% being males. Among the two comparison groups, IL-6 levels were higher in the PIs group (5.65 vs. 7.11 pg/mL,
= 0.03). No statistically significant differences were found in the other measured parameters. A greater proportion of PLWH under INSTIs had normal-range LBP (33% vs. 0%,
= 0.04). When using inverse probability of treatment weighting, no statistically significant differences in the measured parameters were found between the two groups (sCD14
= 0.511, IL-6
= 0.383, SuPAR
= 0.793, I-FABP
= 0.868, and LBP
= 0.663). Glucose levels were found to increase after viral suppression in the entire sample (92 mg/dL vs. 98 mg/dL,
= 0.009). Total (191 mg/dL vs. 222 mg/dL,
= 0.005) and LDL cholesterol (104 mg/dL vs. 140 mg/dL,
= 0.002) levels were higher in the PIs group. No significant differences were observed in liver and renal function tests.
Further investigation is warranted for PLWH on cART-containing INSTI regimens to explore potential reductions in chronic immune activation and intestinal bacterial translocation.
Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy ...of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce.
Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups.
We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%,
= 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07-0.99,
= 0.049) or two (OR 0.06, 95%CI 0.01-0.55,
= 0.014) vaccine booster shots reduced the risk for adverse outcomes.
In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death.
People living with HIV-HCV co-infection comprise a target group for HCV-micro-elimination. We conducted an HCV cascade of care (CoC) for HIV-HCV co-infected individuals living in Greece and ...investigated factors associated with different HCV-CoC stages. We analyzed data from 1213 participants from the Athens Multicenter AIDS Cohort Study. A seven-stage CoC, overall and by subgroup (people who inject drugs (PWID), men having sex with men (MSM), men having sex with women (MSW), and migrants, was constructed, spanning from HCV diagnosis to sustained virologic response (SVR). Logistic/Cox regression models were employed to identify factors associated with passing through each CoC step. Among 1213 anti-HCV-positive individuals, 9.2% died before direct-acting antiviral (DAA) availability. PWID exhibited higher mortality rates than MSM. Of 1101 survivors, 72.2% remained in care and underwent HCV-RNA testing. Migrants and PWID showed the lowest retention rates. HCV-RNA was available for 79.2% of those in care, with 77.8% diagnosed with chronic HCV. Subsequently, 71% initiated DAAs, with individuals with very low CD4 counts (<100 cells/μL) exhibiting lower odds of DAA initiation. SVR testing was available for 203 individuals, with 85.7% achieving SVR. The SVR rates did not differ across risk groups. In 2023, significant gaps and between-group differences persisted in HCV-CoC among HIV-HCV co-infected individuals in Greece.
BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included ...871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1–2 weeks after vaccination or 15–59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651–5583), 6228 (3254–9203) and 7651 (4479–10,823) AU/mL in 35–44, 45–54, 55–70 yrs, respectively, compared with the 18–34 yrs group. In females, the median levels were higher by 2823 (859–4787), 5024 (3122–6926) in individuals with VSE, and 9971 (5158–14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.
Abstract Objectives HIV/hepatitis C virus (HCV) co‐infection among people who inject drugs (PWID) remains a global health problem. The goal of our study was to evaluate, in a real‐world setting, ...success rates of sustained virological response (SVR) using direct‐acting antivirals (DAAs) to treat a population of PWID living with HCV/HIV. Methods This was a prospective single‐center observational study. We collected demographic, socioeconomic, and clinical data pertaining to HIV and HCV infection in PWID with several barriers to care. We identified risk factors for SVR failure. Results Among 130 individuals retained to HIV care, we planned HCV treatment in 119/130 (91.5%); 106/119 (89.1%) started treatment with DAAs and 100/106 (94.3%) completed treatment. People not starting treatment were more often in active opioid drug use (odds ratio OR 0.25; 95% confidence interval CI 0.07–0.97, p = 0.045) and benzodiazepine abuse (OR 0.25; 95% CI 0.07–0.95, p = 0.042). Only 86/100 (86%) were tested for SVR at 12 weeks (SVR12) and 72/86 (83.7%) achieved SVR. PWID in opioid substitution programmes tended to return for SVR12 testing more often (54.7% vs. 30%, p = 0.081). Individuals in active opioid drug use (OR 0.226; 95% CI 0.064–0.793, p = 0.02) or with poor adherence (OR 0.187; 95% CI 0.043–0.814, p = 0.025) were less likely to achieve SVR. At the end of our study period, 113/119 (95%) treatment‐eligible patients remained alive. HCV infection was cured in 68/113 (61.1%) people. Conclusions Our findings underscore the importance of prioritizing combatting substance use to achieve HCV elimination goals. A systematic approach with effort to overcome barriers to receiving and completing treatment and encourage to enrol in opioid substitution programmes if not possible to completely abstain from use, can help increase chances of HCV cure.
Diabetic foot infection is a frequent and potentially life-threatening complication of diabetes mellitus. Antibiotic treatment is the cornerstone of management of diabetic foot infection but the ...rising prevalence of antibiotic resistance has resulted in increasing rates of treatment failure. In this context, the development of several novel antibiotics might represent a useful tool in severe diabetic foot infections caused by multidrug-resistant bacteria. In the present review, we summarize the safety and efficacy of novel antibiotics in patients with diabetic foot infection. Relevant data are limited, and randomized controlled studies that evaluated the role of these agents in this field are lacking. Until more robust data are available, cefiderocol and dalbavancin, which have been studied more extensively in patients with bone infections, might be attractive options in carefully selected patients with severe diabetic foot infection.
Immune checkpoint inhibitors (ICI) have altered the prognosis of patients with melanoma over the past few years, with immune-related adverse effects (irAEs) being the only factor limiting their use. ...Neurologic and cardiac irAEs are rare, but usually severe. We reviewed the files of patients with melanoma treated with ICIs in one center to retrieve data from patients with neurologic irAEs. Patients with a combination of neurologic and cardiac manifestations were further analyzed. We also reviewed the literature for similar syndromes. Five out of 482 (1.01%) patients developed a neurologic syndrome and we present three patients with a constellation of neurologic and cardiac irAEs. A 66-year-old woman and a 68-year-old man presented with a constellation of findings after being treated with ipilimumab and nivolumab, respectively, for melanoma in the adjuvant setting and were eventually diagnosed with myasthenia gravis with cardiac involvement. An 80-year-old woman developed diffuse asymmetric muscle weakness, bilateral ptosis and asymptomatic high serum troponin levels after adjuvant treatment with nivolumab and ipilimumab for a stage IIIB melanoma. After excluding ischemic heart disease, she was diagnosed with axonal polyradiculoneuropathy and myocarditis. Neurologic or cardiac irAEs in patients treated with ICIs are uncommon (<1%), but usually severe, with high rates of morbidity and fatality. The co-development of neurologic and cardiac irAEs is even more rare and can arise soon after exposure to ICIs and escalate rapidly. Since more and more patients are now treated with ICIs in the adjuvant setting, prompt identification and management are essential to avoid serious complications or death.
Background and Objectives: The success of combined antiretroviral therapy (cART) has led to a dramatic improvement in the life expectancy of people living with HIV (PLWH). However, there has been an ...observed increase in cardiometabolic, bone, renal, hepatic, and neurocognitive manifestations, as well as neoplasms, known as serious non-AIDS events/SNAEs, compared to the general population of corresponding age. This increase is linked to a harmful phenomenon called inflammaging/immunosenescence, which is driven by chronic immune activation and intestinal bacterial translocation. In this study, we examined immunological and metabolic parameters in individuals receiving current cART. Materials and Methods: The study was conducted at Laiko General Hospital in Athens, Greece. Plasma concentrations of sCD14, IL-6, SuPAR, I-FABP, and LBP were measured in virally suppressed PLWH under cART with at least 350 CD4 lymphocytes/μL. We compared these levels between PLWH receiving integrase strand transfer inhibitors (INSTIs) and protease inhibitors (PIs) and attempted to correlate them with chronic immune activation and metabolic parameters. Results: Data from 28 PLWH were analyzed, with a mean age of 52 and 93% being males. Among the two comparison groups, IL-6 levels were higher in the PIs group (5.65 vs. 7.11 pg/mL, p = 0.03). No statistically significant differences were found in the other measured parameters. A greater proportion of PLWH under INSTIs had normal-range LBP (33% vs. 0%, p = 0.04). When using inverse probability of treatment weighting, no statistically significant differences in the measured parameters were found between the two groups (sCD14 p = 0.511, IL-6 p = 0.383, SuPAR p = 0.793, I-FABP p = 0.868, and LBP p = 0.663). Glucose levels were found to increase after viral suppression in the entire sample (92 mg/dL vs. 98 mg/dL, p = 0.009). Total (191 mg/dL vs. 222 mg/dL, p = 0.005) and LDL cholesterol (104 mg/dL vs. 140 mg/dL, p = 0.002) levels were higher in the PIs group. No significant differences were observed in liver and renal function tests. Conclusions: Further investigation is warranted for PLWH on cART-containing INSTI regimens to explore potential reductions in chronic immune activation and intestinal bacterial translocation.
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