Latent Tuberculosis Infection in Haematopoietic Stem Cell Transplant Recipients: A Retrospective Italian Cohort Study in Tor Vergata University Hospital, Rome.

The results of tuberculosis (TB) screening and reactivation in a cohort of 323 adult patients undergoing haematopoietic stem cell transplantation (HSCT) from 2015 to 2019 at the University Hospital of Tor Vergata, Rome, Italy, were reported. A total of 260 patients, 59 (18.3%) autologous and 264 (81.7%) allogeneic transplants, underwent Interferon Release (IFN)-γ (IGRA) test screening: 228 (87.7%) were negative, 11 (4.2%) indeterminate and 21 (8.1%) positive. Most of the IGRA-positive patients were of Italian origin (95.2%) and significantly older than the IGRA-negative (p < 0.001); 22 (8.5%) patients underwent a second IGRA during the first year after transplantation, and 1 tested positive for IGRA. Significantly lower monocyte (p = 0.044) and lymphocyte counts (p = 0.009) were detected in IGRA negative and IGRA indeterminate patients, respectively. All latent TB patients underwent isoniazid prophylaxis, and none of them progressed to active TB over a median follow-up period of 63.4 months. A significant decline in TB screening practices was shown from 2015 to 2019, and approximately 19% of patients were not screened. In conclusion, 8.1% of our HSCT population had LTBI, all received INH treatment, and no reactivation of TB was observed during the follow-up period. In addition, 19% escaped screening and 8% of these came from countries with a medium TB burden, therefore at higher risk of possible development of TB.

Hepatitis B-Related Hepatic Flare During Immune Reconstitution Syndrome After Antiretroviral Treatment Initiation in an HBV Surface Antigen-Positive Patient With HIV: Viroimmunological and Histological Characterization.

HIV and hepatitis B virus (HBV) coinfection is relatively common. Initiation of antiretroviral therapy (ART) in people with HIV (PWH) causes a progressive restoration of cell-mediated immune functions. In the presence of overt or occult coinfections, immune restoration might lead to immune reconstitution inflammatory syndrome (IRIS). Here, we describe the clinical, immunological, virological, and histological characterization of a case of HBV-related IRIS hepatitis in a PWH after ART initiation. A liver biopsy was performed during HBV-related IRIS hepatic flare, and liver samples were analyzed through immunohistochemistry and molecular techniques, with the assessment of intrahepatic HBV-DNA, covalently closed circular DNA, and HBV pregenomic RNA through a droplet digital polymerase chain reaction system. Immune activation and senescence were also longitudinally assessed. In this clinical case, the hepatic flare occurred 6 weeks after ART initiation with a therapeutic regimen including tenofovir alafenamide (TAF) and emtricitabine (FTC). The episode was self-limiting, characterized by hyperactivation of peripheral blood CD4+ and CD8+ T-lymphocytes, and resolved without ART discontinuation, leading to the achievement of HBsAg seroconversion (HBsAg-/HBsAb+) and HBV-DNA plasma undetectability. Notably, hyperactivation of the immune system plays a pivotal role in promoting the control of HBV replication, thus triggering the achievement of HBsAg seroconversion during treatment with TAF/FTC.

Inhaled antibiotics for treatment of adults with non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis.

BACKGROUND: Inhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations. METHODS: We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154. RESULTS: Twelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70-5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81-18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28-1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82-0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV1, mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35-3.27) at the end of therapy, with a number needed to treat of 6. CONCLUSIONS: IA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes.

Acute respiratory failure among lung transplant adults requiring intensive care: Changing spectrum of causative organisms and impact of procalcitonin test in the diagnostic workup.

BACKGROUND: The aim was to identify the causing organisms and assess the association of procalcitonin (PCT) with bacterial pneumonia within 24 hours of intensive care unit admission (ICU-A) among lung transplant (LT) adult recipients. METHODS: Secondary analysis from a prospective cohort study. All LT adults admitted to ICU for acute respiratory failure (ARF) over 5 years were included. Patients were followed until hospital discharge or death. RESULTS: Fifty-eight consecutive LT patients were enrolled. The most important cause of ICU-A due to ARF was pneumonia 29 (50%) followed by acute rejection 3 (5.2%) and bronchiolitis obliterans syndrome exacerbation 3 (5.2%). Microorganisms were isolated from 22/29 cases with pneumonia (75.9%): 17 (77.2%) bacterial, 4 (18.2%) viral, 1 (4.5%) Aspergillus fumigates, with Pseudomonas aeruginosa being the most common cause (45.5%) of pneumonia, with 10 patients presenting chronic colonization by P aeruginosa. Median [Interquartile range (IQR)] PCT levels within 24 hours after admission were higher in pneumonia (1.5 µg/L; IQR:0.3-22.0), than in non-pneumonia cases (0.2 µg/L; IQR:0.1-0.7) (P = .019) and PCT levels within 24 hours helped to discriminate bacterial pneumonia (8.2 µg/L; IQR:0.2-43.0) from viral pneumonia and non-pneumonia cases (0.2 µg/L; IQR:0.1-0.7). The overall negative predictive value for bacterial pneumonia was 85.1%, increasing to 91.6% among episodes after 6 months of LT. CONCLUSIONS: Causes of severe pneumonia in LT are changing, with predominant role of P aeruginosa and respiratory viruses. PCT ≤ 0.5 µg/L within 24 hours helps to exclude bacterial pneumonia diagnosis in LT adults requiring ICU-A. A negative PCT test allows antimicrobial de-escalation and requires an alternative diagnostic to bacterial pneumonia.

Remission of an HHV8-related extracavitary primary effusion lymphoma in an HIV-positive patient during antiretroviral treatment containing dolutegravir.

BACKGROUND: Human herpes virus 8 (HHV8) is the causative agent of Kaposi's sarcoma and has been associated with an increasing number of hematologic diseases such as primary effusion lymphoma (PEL) (both classic and extracavitary form), multicentric Castleman disease and the germinotropic lymphoproliferative disorder. PEL is a rare B cell non-Hodgkin lymphoma that primarily affects immunocompromised patients; aggressive chemotherapy and antiretroviral therapy (ART) with protease inhibitors have been used, with poor results. We present a case of extracavitary PEL in an HIV-infected patient, regressed after ART initiation. CASE PRESENTATION: A 42-year-old male was admitted to the emergency room because of several months of malaise, fever and progressive deterioration of the general conditions. On physical examination soft non-painful subcutaneous masses were palpable at retronuchal, retroauricolar and thoracic regions. HIV serology resulted positive: HIV plasma viremia was 782,270 copies/mL, CD4 103 cells/mL. The excision of one of the masses, metabolically active at a positron emission tomography (PET-CT) scan, revealed an HHV8-related extracavitary PEL. HHV8 plasma viremia was 44,826 copies/mL. ART with tenofovir alafenamide/emtricitabine/dolutegravir was started together with ganciclovir for cytomegalovirus chorioretinitis. The progressive disappearance of the masses was seen after 6 weeks of ART, and a PET-CT scan resulted completely negative at 3 months. After 19 months of ART the patient was in remission of PEL, HIV viremia was undetectable (< 20 copies/mL), CD4 count was 766 cells/mL and HHV8 viremia was undetectable. CONCLUSIONS: In this clinical case, the complete regression of PEL has been achieved after the immune recovery, as a consequence of ART introduction, without chemotherapy. It cannot be excluded that ganciclovir, used for the treatment of CMV chorioretinitis, may have contributed to the control of HHV8 replication. Whether to try or not a conservative approach in HIV-infected PEL patients must be carefully evaluated, considering the patient's characteristics and the prognostic factors.