Ospedale Amedeo di Savoia

Post-tuberculosis lung disease (PTLD) is an increasingly recognized condition that significantly affects survivors' quality of life, creating disability and incrementing the risk of mortality. PTLD includes a spectrum of structural and functional lung impairments such as obstructive, restrictive, and mixed patterns, bronchiectasis, and pulmonary fibrosis that persist beyond microbiological cure. Global prevalence data highlight a heavy burden of PTLD, especially in high-incidence regions, driven by late diagnosis and suboptimal treatment. Functional and radiological evaluation remains critical for timely diagnosis, with spirometry and imaging revealing lasting abnormalities in a large proportion of TB survivors. Multidisciplinary care is essential and includes bronchodilator therapy, infections/complications management and prevention, pulmonary rehabilitation, and, in selected cases, surgical intervention. Despite increasing recognition, standardized diagnostic and therapeutic pathways for PTLD are still lacking, and data on optimal follow-up, rehabilitation strategies, and preventive measures remain limited. Prospective studies, better stratification tools, and patient education initiatives are urgently needed to reduce PTLD morbidity and mortality. This narrative review synthesizes current evidence on PTLD epidemiology, clinical evaluation and management while offering practical suggestions for clinicians taking care of people with TB and addressing research needs.

Aim of the study wasto define the patterns and determinants of symptom persistence in Long-COVID. The study population was represented bya multicenter cohort of patients with persisting symptoms after SARS-CoV-2 infection. Data collection included demographics, comorbidities, characteristics of acute infection, vaccination, reinfection, plus 30 different symptoms. The associations between covariates and persistence were assessed in multivariable logistic regression models. The study evaluated, at a mean interval of 453 days from acute SARS-CoV-2 infection, symptom persistence in 755 patients who had Long-COVID symptoms at a mean interval of 223 days from COVID-19. At second evaluation, 423 (56.0%) patients still presented one or more symptoms and 332 (44.0%) were symptom free. In those who remained symptomatic, the mean number of symptoms significantly reduced between the two evaluations. Compared to the first evaluation, the overall mean symptom regression rate was 72%, with lower regression rates observed for dyspnea (53%), anxiety (54%) and sleep disturbances (55%). The risk of persistence was increased for female sex, higher BMI, hospitalization and stronger ventilatory support during acute disease, higher number of initial symptoms and particular comorbidities (anxiety, chronic pulmonary disease, asthma), and decreased with the increase of age and time from acute SARS-CoV-2 infection. Neither SARS-CoV-2 vaccination nor reinfection showed significant associations with persistence. In this case series, roughly half of the patients that were symptomatic 7 months after acute SARS-CoV-2 infection remained symptomatic after an additional 7 months. The pattern and predictors of persistence draw attention to certain particular risk factors and manifestations that tend to persist longer than others.

IntroductionThe olive tree (Olea europaea L.) has cultural, economic, and environmental importance in the Mediterranean region. In the last two decades, olive cultivation has shifted from low-density to super high-density (SHD) planting systems. These systems are characterized by narrow hedgerows of low-vigor, early-bearing cultivars, allowing full mechanization. However, limited information are available on shoot growth dynamics of the olive tree under the SHD system. This study aimed to investigate the shoot growth dynamics of four olive cultivars (‘Arbequina’, ‘Coratina’, ‘Frantoio’, and ‘Urano’) by modeling the elongation of different shoot types (apical proleptic, lateral proleptic, sylleptic) under SHD conditions.MethodsA four-year field study was conducted on four olive cultivars (‘Arbequina’, ‘Coratina’, ‘Frantoio’, and ‘Urano’) grown in an SHD orchard under Mediterranean climate. Apical proleptic, lateral proleptic, sylleptic, and adventitious shoots were monitored. Logistic regression was applied to model shoot elongation, and statistical analyses were conducted to assess the influence of cultivar, shoot type, and year. Moreover, the effect of crop load and temperature on shoot growth was also evaluated.Results and DiscussionNo significant difference was shown between the type of shoot and cultivar. Results indicate that single-phase logistic growth was the most common pattern, except for the lateral proleptic shoots of ‘Coratina’ and adventitious of ‘Urano’, where a second vegetative flush occurred. No correlation of Growing Degree Days with the shoot growth was observed. As confirmed in previous studies, crop load showed a negative influence on shoot elongation. Particularly for Arbequina’s adventitious shoots, Coratina’s and Frantio’s sylleptic shoots and Urano’s lateral proleptic, this trend was observed. This evidence showed the potential competition between the reproductive and vegetative cycle for assimilates. To our knowledge, this is the first report addressing the vegetative growth dynamics of four different shoot types of four distinct olive cultivars with different vigor in an SHD system. These findings are essential for optimizing cultivar-specific agricultural strategies (e.g. canopy management and irrigation) to achieve an optimal yield and sustainable cultivation. Future research will explore the vegetative growth dynamics, including other factors such as trunk diameter, Leaf Area Index, and water stress indices.

In 2023, the Italian healthcare system launched HCV screening targeting subjects born in 1968–1989. However, subjects > 50 yrs also need screening. In addition, existence of gender gaps in HCV diagnosis and treatment has been suggested. Our aim was to identify undiagnosed individuals outside the age groups to whom the screening is offered and to gather data about gender gaps. This is a prospective, opportunistic micro-elimination initiative based on a network between 24 Apulian pharmacies and our center. Between 01/07/2022 and 01/03/2024, subjects aged 55 to 85, accessing pharmacies were offered HCVOraQuick tests (F/M 1:1) and administered ad-hoc questionnaires. In total, 13,042 screening were carried out. Mean age was 64.9 (± 7.6), 51.1% females. Overall, 1.1% were anti-HCV positive: mean age 68.3 (± 10.3), 44.9% females. Seroprevalence was higher in males (p < 0.00001), elderly (p < 0.00001) and unknown transmission route (p = 0.0009). HCV-RNA was detectable in 67.4% of seropositive. They were 67.5 (± 10.7) yrs old, mainly males (55.1%). HCV-RNA prevalence was 0.8%, higher in elderly (p = 0.0003) and unknown transmission route (p = 0.0007). Overall, 90% were linked-to-treatment. Differences in patients profiles should be considered to guide policy and more inclusive treatment approaches. Gender differences in screening response and rates of active infections underscore the need for gender-targeted intervention.

Modern ART is evolving, allowing the use of new drug formulations and alternative routes of administration to oral therapy. Long-acting (LA) cabotegravir and rilpivirine, the first fully injectable antiretroviral regimen approved for clinical use, is a test case for this new route of administration, and an innovation with implications for the quality of life of people with HIV (PWH). However, its use requires a reorganization of outpatient clinics and outpatient services, and a number of issues remain to be defined regarding the management of PWH on LA drugs, including the correct selection of people who can be treated with LA cabotegravir and rilpivirine. There is also ongoing debate about the best way to monitor both efficacy and tolerability of LA treatment and whether the management of virological failures and blips should be different from that reserved for oral regimens. The present article reviews the data on the use and management of LA cabotegravir and rilpivirine in different settings, with a review of clinical trial data and also the first available real-life experiences. The article focuses on the following: the reasons for the use of LA drugs; the implementation of their use in clinical practice; and the monitoring of treated people over time.

ABSTRACT Introduction Infectious disease treatments are transitioning from a one-size-fits-all approach to a more tailored approach. The increasing adoption of therapeutic drug monitoring (TDM) of antimicrobials is a clear example of this trend. Routine antimicrobial TDM in critically ill patients should be mandatory. Unfortunately, nowadays, only expert centers can provide it. Given the crucial nature of the first hours/days for achieving a favorable clinical outcome, empirical antibiotic therapy with an adequate choice of drug, dose and administration modalities is fundamental. Areas covered We outline common scenarios encountered in clinical practice, such as in edematous patients, hypoalbuminemia, patients with liver and renal diseases, patients under renal replacement therapy or extracorporeal membrane oxygenation (ECMO), over or under-weight patients, in old adults and cases of infections caused by relatively high minimum inhibitory concentration (MIC) pathogens. Various clinical situations were analyzed with the help of the available literature (PubMed/MEDLINE/Google Scholar and books written by experts in pharmacology and infectious diseases). Expert opinion In these different scenarios, we reported common examples of optimizing drug utilization to maximize therapeutic outcomes, reduce incorrect prescriptions and limit the emergence of antimicrobial resistance.

BackgroundTuberculosis (TB) incidence in Angola in 2022 was 333 cases per 100,000 people. Treatment coverage is suboptimal and treatment failure is common. TB case fatality rate is 20% and an estimated 17,000 TB cases were attributable to HIV. The aim of this study was to describe the characteristics of patients admitted to the TB ward of an urban hospital in Luanda in 2023.MethodsWe performed a retrospective review of medical records of patients admitted to the TB ward of the Hospital Divina Providência (HDP) in Luanda between January and November 2023. We gathered data on demographics, medical history, laboratory and imaging tests, treatment, and outcome from patients‘ medical records. We assessed factors associated with in-hospital mortality using binary logistic regression.ResultsWe enrolled 321 participants. The median age was 35 years (Interquartile range [IQR]: 25, 47) and 48.6% were males. Median weight was 48 Kg (IQR: 41, 53) with malnutrition reported for 119 participants (37.1%). One hundred twenty-eight individuals (39.9%) had a previous history of TB. HIV test was requested and performed for 206 and 142 participants respectively. Of the 142 tests performed 96 (67.6%) were HIV-positive. Microbiologically-confirmed TB (positive sputum staining or gene Xpert) was observed in 5 patients only (1.6%). Fifty-eight of 321 (18%) patients died during hospital admission. The in-hospital mortality among patients with known HIV-status was 28%. At multivariate analysis dyspnea at admission (adjusted odds ratio [aOR] 2.7, p=0.001), HIV positivity (aOR 2.5, p=0.004) and malnutrition (aOR 2.4, p=0.006) were independent predictors of in-hospital mortality.ConclusionsOur findings suggest that TB is mainly diagnosed on clinical grounds. The prevalence of HIV is high. Timely diagnosis and tailored treatments including management of significant risk factors such as malnutrition and HIV infection are warranted to improve clinical outcomes and reduce in-hospital mortality in this vulnerable population.

BackgroundThe use of combination regimens is paramount in the treatment of HIV infection. Virologically suppressed patients, may benefit to change their treatment in a two-drug regimen (2DR). Long acting (L-A) injectable 2DR may be a good option in selected patients (preference for a nondaily dosing, toxicity to oral therapy, prevention of long-term toxicity, adherence issues, dysphagia). The aim of this cohort study is to define the medical reasons (viral failure vs. others) and the changes in GRT in interruption of cabotegravir-rilpivirine (CAB-RPV) regimen in an Italian cohort of PWH who were subjected to a L-A injectable regimen according to prescriptive indications.MethodsWe analyzed the data supplied by 9 infectious diseases units, where CAB-RPV regimen is available and administered, to make a descriptive analysis of the causes of interruption and the impact of genotyping drug resistance, when available.ResultsThe total of patients receiving CAB-RPV was 574; 51 interrupted the treatment. The average age of the patients of this cohort was 54 years and average BMI was 24,8 kg/m2 (BMI max 44.28 kg/m2). Before starting the injectables, 28 patients took a triple oral therapy (regimen mostly used: TAF/FTC/RPV), while 22 assumed a 2DR regimen (regimens mostly used: DTG/3TC-DTG/RPV); as a whole, 32 took an INSTI-based regimen. Only one PWH received a mono therapy. 13 had an oral lead in. As far as the genotypic resistance pattern, 33 patients had a GRT before starting CAB-RPV; 1 patient had documented resistance to NNRTI (138A, which is an important risk factor of viral failure of RPV), while none had INSTI resistance. We collected 11 documented viral failures. All of them carried out a GRT post VF; the results are shown in table 1. The other 40 patients interrupted L-A therapy for other reasons (local pain, adverse events, toxicity, patient‘s choice, drugs interactions). The mean time of duration of L-A regimen was 5.3 months: 5.8 (+/- 4.73 SD) months for patients with VF and 5.25 (+/- 4.13 SD) for patients who interrupted for other reasons, without statistical significance. OC-11 Table 1ConclusionsOne. seven% of our cohort experienced a VF; this result is coherent with the main studies evaluating a low failure rate of CAB-RPV. NNRTI and INSTI mutations that arose during L-A treatment were all associated with a documented VF. CAB-RPV L-A regimen was well-tolerated in our cohort. Respect of eligibility criteria and awareness of risk factors for VF plus strict monitoring of viro-immunological parameters are fundamental in reducing the risk of VF and the possible onset of new NNRTI/INSTI resistance mutations.

Background: Physical activity could increase the production of oxidative stress biomarkers, affecting the metabolism and excretion of antiretroviral drugs and, consequently, the clinical outcome. Nowadays, people living with HIV (PLWH) are mostly switching from triple to dual therapy, but no data are available in terms of physical functioning and oxidative stress. The aim of this study was to evaluate if some antioxidant biomarkers and physical functioning tests could be different according to triple or dual antiretroviral therapy. Methods: PLWH were evaluated at baseline (BL), while treated with three drugs, and six months after the switch to dual therapy. Physical functioning was quantified using validated tools. Mitochondrial and cytosol antioxidant molecules were evaluated through liquid chromatography. Results: Twenty-five patients were analyzed. A statistically significant difference between triple and dual therapy was found for mitochondrial glutathione, but not for physical tests. Evaluating differences between physically active and inactive individuals, the following statistically significant differences were suggested, considering triple therapy (mitochondrial n-formyl-methionine p = 0.022, triglycerides p = 0.023) and double therapy (mitochondrial glycine p = 0.035, cytosol glutamic acid p = 0.007, cytosol s-adenosylmethionine p = 0.021). Conclusions: For the first time, this study suggests possible differences in terms of antioxidant molecules and physical functioning in PLWH switching from triple to dual therapy.