Idiopathic pulmonary fibrosis (IPF) is a chronic progressive degenerative lung disease leading to respiratory failure and death. Although anti-fibrotic drugs are now available for treating IPF, their ...clinical efficacy is limited and lung transplantation remains the only modality to prolong survival of IPF patients. Despite its limitations, the bleomycin (BLM) animal model remains the best characterized experimental tool for studying disease pathogenesis and assessing efficacy of novel potential drugs. In the present study, the effects of oropharyngeal (OA) and intratracheal (IT) administration of BLM were compared in C57BL/6 mice. The development of lung fibrosis was followed
in vivo
for 28 days after BLM administration by micro-computed tomography and
ex vivo
by histological analyses (bronchoalveolar lavage, histology in the left lung to stage fibrosis severity and hydroxyproline determination in the right lung). In a separate study, the antifibrotic effect of Nintedanib was investigated after oral administration (60 mg/kg for two weeks) in the OA BLM model. Lung fibrosis severity and duration after BLM OA and IT administration was comparable. However, a more homogeneous distribution of fibrotic lesions among lung lobes was apparent after OA administration. Quantification of fibrosis by micro-CT based on % of poorly aerated tissue revealed that this readout correlated significantly with the standard histological methods in the OA model. These findings were further confirmed in a second study in the OA model, evaluating Nintedanib anti-fibrotic effects. Indeed, compared to the BLM group, Nintedanib inhibited significantly the increase in % of poorly aerated areas (26%) and reduced
ex vivo
histological lesions and hydroxyproline levels by 49 and 41%, respectively. This study indicated that micro-computed tomography is a valuable
in vivo
technology for lung fibrosis quantification, which will be very helpful in the future to better evaluate new anti-fibrotic drug candidates.
Background
Patients with hematological malignancies (HM) have a high risk of severe coronavirus disease 2019 (COVID‐19), also in the Omicron period.
Material and methods
Retrospective single‐center ...study including HM patients with severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV2) infection from January 2022 to March 2023. Study outcomes were respiratory failure (RF), mechanical ventilation (MV), and COVID‐related mortality, comparing patients according to SARS‐CoV2 serology.
Results
Note that, 112 patients were included: 39% had negative SARS‐CoV2 serology. Seronegative were older (71.5 vs. 65.0 years, p = 0.04), had more often a lymphoid neoplasm (88.6% vs. 69.1%, p = 0.02), underwent anti‐CD20 therapy (50.0% vs. 30.9% p = 0.04) and had more frequently a severe disease (23.0% vs. 3.0%, p = 0.02) than seropositive.
Kaplan‐Meier showed a higher risk for seronegative patients for RF (p = 0.014), MV (p = 0.044), and COVID‐related mortality (p = 0.021). Negative SARS‐CoV2 serostatus resulted in a risk factor for RF (hazards ratio HR 2.19, 95% confidence interval CI 1.03–4.67, p = 0.04), MV (HR 3.37, 95% CI 1.06–10.68, p = 0.04), and COVID‐related mortality (HR 4.26, 95% CI 1.09–16.71, p = 0.04).
Conclusions
: HM patients with negative SARS‐CoV2 serology, despite vaccinations and previous infections, have worse clinical outcomes compared to seropositive patients in the Omicron era. The use of serology for SARS‐CoV2 diagnosis could be an easy tool to identify patients prone to developing complications.
Bovine herpesvirus 4 (BoHV-4) is a promising vector for the delivery and intracellular expression of recombinant antigens and can thus be considered as a new prototype vaccine formulation system. An ...interesting, and actively pursued, antigen in the context of human immunodeficiency virus (HIV) infection prophylaxis (and therapy) is the C-C chemokine receptor type 5 (CCR5) co-receptor, whose blockage by specific antibodies has been shown to inhibit both viral entry and cell-to-cell transmission of the virus. Building on our previous work on the BoHV-4 vector system, we have engineered and tested a replication-competent derivative of BoHV-4 (BoHV-4-CMV-hCCR5ΔTK) bearing a human CCR5 (hCCR5) expression cassette. We show here that CCR5 is indeed expressed at high levels in multiple types of BoHV-4-CMV-hCCR5ΔTK-infected cells. More importantly, two intravenous inoculations of CCR5-expressing BoHV-4 virions into rabbits led to the production of anti-CCR5 antibodies capable of reacting with the CCR5 receptor exposed on the surface of HEK293T cells through specific recognition of the amino-terminal region (aa 14-34) of the protein. Given the growing interest for anti-CCR5 immunization as an HIV control strategy and the many advantages of virus-based immunogen formulations (especially for poorly immunogenic or self-antigens), the results reported in this study provide preliminary validation of BoHV-4 as a safe viral vector suitable for CCR5 vaccination.
OBJECTIVE:The aim was to investigate the contribution of liver steatosis and significant fibrosis alone and in association nonalcoholic fatty liver disease (NAFLD) with fibrosis to frailty as a ...measure of biological age in people living with HIV (PLWH).
DESIGN:This was a cross-sectional study of consecutive patients attending Modena HIV Metabolic Clinic in 2018–2019.
METHODS:Patients with hazardous alcohol intake and viral hepatitis coinfection were excluded. Liver steatosis was diagnosed by controlled attenuation parameter (CAP), while liver fibrosis was diagnosed by liver stiffness measurement (LSM). NAFLD was defined as presence of liver steatosis (CAP ≥248 dB/m), while significant liver fibrosis or cirrhosis (stage ≥F2) as LSM at least 7.1 kPa. Frailty was assessed using a 36-Item frailty index. Logistic regression was used to explore predictors of frailty using steatosis and fibrosis as covariates.
RESULTS:We analysed 707 PLWH (mean age 53.5 years, 76.2% men, median CD4 cell count 700 cells/μl, 98.7% with undetectable HIV RNA). NAFLD with fibrosis was present in 10.2%; 18.9 and 3.9% of patients were classified as frail and most-frail, respectively. Univariate analysis demonstrated that neurocognitive impairment odds ratio (OR) = 5.1, 1.6–15, vitamin D insufficiency (OR = 1.94, 1.2–3.2), obesity (OR = 8.1, 4.4–14.6), diabetes (OR = 3.2, 1.9–5.6), metabolic syndrome (OR = 2.41, 1.47–3.95) and osteoporosis (OR = 0.37, 0.16–0.76) were significantly associated with NAFLD with fibrosis. Predictors of frailty index included steatosis (OR = 2.1, 1.3–3.5), fibrosis (OR = 2, 1–3.7), NAFLD with fibrosis (OR = 9.2, 5.2–16.8), diabetes (OR = 1.7, 1–2.7) and multimorbidity (OR = 2.5, 1.5–4).
CONCLUSION:Liver steatosis and NAFLD with fibrosis were associated with frailty. NAFLD with fibrosis exceeded multimorbidity in the prediction of frailty, suggesting the former as an indicator of metabolic age in PLWH.
Background
Since February 2021 active screening of COVID‐19‐associated pulmonary aspergillosis (CAPA) has been implemented in our institution.
Objectives
To evaluate CAPA incidence in our centre and ...evaluate performance of our screening protocol.
Methods
We screened once per week, collecting endotracheal aspirates for fungal culture and galactomannan (GM) and serum for 1,3‐ß‐D‐glucan (BG). In case of positivity (GM more than 4.5, platelia assay, and/or BG >7 pg/ml, wako and/or positive fungal culture), second‐level investigations were performed to pursue CAPA diagnosis according to ECMM/ISHAM criteria: bronchoalveolar lavage (BAL) fungal culture and GM, chest computed tomography (CT), serum GM.
Results
A total of 102 patients were screened (median age 64 years, range 39–79; 28 (27.4%) females). Twenty‐two patients were diagnosed with CAPA (21%). 12 patients were positive for serum BG, 17 patients were positive for endotracheal aspirates GM and 27 patients were positive for endotracheal aspirates fungal culture. Thirty‐two BALs were performed, and 26 patients underwent CT chest. Following the second level investigations 61% of the patients with positive screening tests were diagnosed with CAPA. Serum BG above 20 pg/ml or positive serum GM were always associated with typical CT chest signs of aspergillosis. Compared with 1 single positive test, having 2 positive screening test was significantly more associated with CAPA diagnosis (p = .0004).
Conclusions
Active CAPA screening with serum 1,3‐ß‐D‐glucan and endotracheal aspirates galactomannan and fungal cultures and consequent second level investigations led to high number of CAPA diagnosis. Combining more positive fungal biomarkers was more predictive of CAPA diagnosis.
OBJECTIVE:The aim was to investigate the contribution of liver steatosis and significant fibrosis alone and in association (NAFLD with fibrosis) to frailty as a measure of biological age in people ...living with HIV (PLWH).
DESIGN:This was a cross-sectional study of consecutive patients attending Modena HIV Metabolic Clinic in 2018-2019.
METHODS:Patients with hazardous alcohol intake and viral hepatitis co-infection were excluded. Liver steatosis was diagnosed by controlled attenuation parameter (CAP), while liver fibrosis was diagnosed by liver stiffness measurement (LSM). NAFLD was defined as presence of liver steatosis (CAP≥248), while significant liver fibrosis or cirrhosis (stage ≥F2) as LSM≥7.1 kPa. Frailty was assessed using a 36-Item frailty index (FI). Logistic regression was used to explore predictors of frailty using steatosis and fibrosis as covariates.
RESULTS:We analyzed 707 PLWH (mean age 53.5 years, 76.2% males, median CD4 700 μL, 98.7% with undetectable HIV RNA). NAFLD with fibrosis was present in 10.2%; 18.9% and 3.9% of patients were classified as frail and most-frail, respectively. Univariate analysis demonstrated that neurocognitive impairment (OR = 5.1, 1.6–15), vitamin D insufficiency (OR = 1.94, 1.2–3.2), obesity (OR = 8.1, 4.4–14.6), diabetes (OR = 3.2, 1.9–5.6) and osteoporosis (OR = 0.37, 0.16–0.76) were significantly associated with NAFLD with fibrosis. Predictors of FI includedsteatosis (OR = 2.1, 1.3–3.5), fibrosis (OR = 2, 1–3.7), NAFLD with fibrosis (OR = 9.2, 5.2–16.8), diabetes (OR = 1.7, 1–2.7) and multimorbidity (OR = 2.5, 1.5–4).
CONCLUSION:Liver steatosis and NAFLD with fibrosis were associated with frailty. NAFLD with fibrosis exceeded multimorbidity in the prediction of frailty, suggesting the former as an indicator of metabolic age in PLWH.
Psychological distress represents a longstanding issue that has been observed in university student populations. The present study aimed to explore the psychological distress in a group of university ...students seeking for psychological help available in an Italian University Counselling Service. Participants were 597 students (70.5% female, M
age
= 24.79, SD
age
= 5.08) who consulted the Psychological Service at the University and completed the Adult Self-Report (ASR) questionnaire prior to a brief psychodynamic intervention (T1) and 372 of them (70.4% females, M
age
= 24.85, SD
age
= 5.44) were re-evaluated on the same scales three months after the end of the intervention within a follow-up session. Findings demonstrated that students who dropped out at follow-up had slightly higher baseline scores in Thought Problems and Rule-Breaking Behavior. Adopting a Latent Change Score Difference (LDS) approach to model the differences between T1 and T2 scores in ASR scales, results showed an average significant and reliable decrease in all psychopathological syndromes, although the rate of this change was not uniform for all individuals (in the case of somatic complaints, this was partially accounted for by gender). Students reporting higher symptoms in three syndromes at T1 (i.e., somatic complaints, depressive symptoms, withdrawal) showed a steeper decrease of such scores at the follow-up. Findings suggest that a short-term psychological counselling intervention may represent an efficacious way to deal with emerging psychopathological distress within university contexts
.
Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson's Disease (PD). However, the effects of STN-DBS on speech are still debated, ...particularly in the long-term follow-up. The objective of this study was to evaluate the long-term effects of bilateral STN-DBS on speech in a cohort of advanced PD patients treated with bilateral STN-DBS. Each patient was assessed before surgery through a neurological evaluation and a perceptual-acoustic analysis of speech and re-assessed in the long-term in different stimulation and drug conditions. The primary outcome was the percentage change of speech intelligibility obtained by comparing the postoperative on-stimulation/off-medication condition with the preoperative off-medication condition. Twenty-five PD patients treated with bilateral STN-DBS with a 5-year follow-up were included. In the long-term, speech intelligibility stayed at the same level as preoperative values when compared with preoperative values. STN-DBS induced a significant acute improvement of speech intelligibility (p < 0.005) in the postoperative assessment when compared to the on-stimulation/off-medication and off-stimulation/off-medication conditions. These results highlight that STN-DBS may handle speech intelligibility even in the long-term.
PDF
