Relapsing bronchiolitis obliterans organising pneumonia and chronic sarcoidosis in an atopic asthmatic patient

Asthma is thought to be a Th2 disease while sarcoidosis is considered a Th1 granulomatous disorder. Organising pneumonia is a histologic pattern of lung injury. When it has no recognisable cause it is defined as cryptogenic organising pneumonia. We herein report the case of a patient with recurrent and steroid sensitive organising pneumonia associated with chronic sarcoidosis in an atopic, moderate persistent asthmatic patient. Each disease has been documented with transbronchial biopsies and recurrence of organising pneumonia was suggested by clinical features and by follow up HRCT which shows distinctive signs even in associated disease. Steroids are the mainstay of therapy for these disorders and especially for the consolidated processes typical of organising pneumonia but prognostic indices for relapse and progression are lacking

The Impact of COVID-19 Lockdown Announcements on Mental Health: Quasi-Natural Experiment in Lombardy, Italy

Background: Evidence showed that mental health problems have risen markedly during COVID-19. It is unclear if part of the mental sufferings relates to the climate of uncertainty and confusion originated by rough communication by health officials and politicians. Here we test the impact of unanticipated policy announcements of lockdown policies on mental health of the older population. Methods: We used a representative telephone-based survey of 4,400 people aged 65\u2009years or older in Italy's Lombardy region to compare information on self-reported symptoms of anxiety, depression, and poor-quality sleep of subjects interviewed on the days of policy announcement with that of subjects interviewed on other days. We used regression models adjusting for potential socio-demographic confounders as well study design with inverse probability weighting. Results: On days when policy makers announced to extend the lockdown, mental health deteriorated on average by 5.5 percentage points [95% CI: 1.1 to 9.8] for self-reported anxiety symptoms and 5.1 percentage points [95% CI: 2.7 to 7.4] for self-reported depressive symptoms. The effect of announcement to shorten the lockdown is more moderate but statistically significant. These associations were short term in duration; after just one day, self-reported mental health and sleep quality return to levels better than pre-announcement until a new policy change. Conclusions: Our research shows that lockdown policy announcements are associated with short term worsening in mental distress, highlighting the importance of appropriate communication strategies and political determinations in crisis times

Influence of the Occlusion Site

Background: Previous findings suggest that transient myocardial ischemia and reperfusion may elicit changes in the autonomic balance. In this study, a spectral analysis of heart rate variability was used to assess the modifications of sympathovagal balance induced by coronary angioplasty and their relationship with the occlusion site. Methods: We studied 23 patients (17M, 6F, age 58 ± 10 years) with left anterior descending and 19 patients (15M, 4F, age 56 ± 9 years) with right coronary artery stenosis. Spectral analysis of heart rate variability was performed, by autoregressive model, in basal conditions and during each balloon inflation. At least two inflations of 90–120 seconds were performed in each patient. Results: In patients with left anterior descending artery stenosis, the first occlusion induced marked changes in the autonomic balance, which moved toward a sympathetic predominance. The low frequency component of the spectrum and the low-to-high frequency ratio increased from 59 ± 10 normalized units (NU) to 75 ± 10 NU (P < 0.001) and from 2.4 ± 1.4 to 7.3 ± 4.7 (P < 0.001) respectively, while the high frequency component decreased from 30 ± 11 NU to 14 ± 7 NU (P < 0.001). These changes showed a progressive attenuation during repetitive occlusions, and were significantly correlated with the entity of myocardial ischemia assessed by the ST-segment shift measured on the intracoronary electrocardiographic lead. On the contrary, in patients with right coronary artery stenosis the first occlusion was ineffective with regard to the spectral parameters whereas the third occlusion induced a significant increase in the high frequency component (from 31 ± 9 NU to 41 ± 10 NU, P < 0.01) and decrease in the low-to-high frequency ratio (from 2.1 ± 0.9 to 1.3 ± 0.5, P < 0.05) suggesting a vagal activation. The entity of vagal activation was not correlated with the ST-segment shift. Conclusions: Our data indicate that repetitive coronary occlusions induce significant changes in the autonomic balance. The direction and the time course of these changes are related to the occlusion site

Comparison of Fluoroquinolones and Other Antibiotic Prophylaxis Regimens for Preventing Complications in Patients Undergoing Transrectal Prostate Biopsy

: Our study aimed to compare the incidence of infective complications after transrectal ultrasound-guided prostate biopsy (TRUSBx) when adopting different antimicrobial prophylaxis regimens. A multi-institutional cohort of 1150 patients who underwent TRUSBx was retrospectively analyzed. Procedures were performed between 2017 and 2019 (before and after the EMA warning about the use of fluoroquinolones for the antibiotic prophylaxis of patient candidates to TRUSBx). The primary endpoint was the occurrence of infective complications, including sepsis and/or fever. The population was stratified according to the antibiotic prophylaxis adopted: fluoroquinolones (levofloxacin, ciprofloxacin, prulifloxacin), cephalosporins (cefixime, ceftriaxone) or trimethoprim/sulfamethoxazole. Univariable and multivariable binomial logistic regression models were used to assess the odds ratio (OR) with 95% confidence interval (CI) testing of the risk of infective complication after adjusting for each prebiopsy covariate. In total, 478 (41.6%) patients received fluoroquinolone-based prophylaxis. Among these, 443 (38.5%), 25 (2.2%) and 10 (0.9%) patients received levofloxacin prophylaxis, ciprofloxacin and prulifloxacin, respectively while 14.6% received cefixime, 20.7% received the comedication of ceftriaxone/fosfomycin and 23.1% received trimethoprim/sulfamethoxazole. The trimethoprim/sulfamethoxazole and fluoroquinolone regimens were significantly associated with a lower risk of infective complications (OR 0.15, 95% CI 0.03-0.48, p = 0.003 and OR 0.17, 95% CI 0.06-0.43, p &lt; 0.001, respectively). The ceftriaxone/fosfomycin (OR 0.21, 95% CI 0.04-0.92, p = 0.04) and fluoroquinolone (OR 0.07, 95% CI 0.00-0.70, p = 0.048) prophylaxis were associated with a lower risk of infective sequelae. Fluoroquinolone-based prophylaxis was associated with a lower risk of infective complications after TRUSBx compared to other prophylaxis regimens although its clinical application was recently forbidden by European Medical Agency restrictions

Older Adults' Access to Care during the COVID-19 Pandemic: Results from the LOckdown and LifeSTyles (LOST) in Lombardia Project

: The COVID-19 pandemic disproportionally affected older people in terms of clinical outcomes and care provision. We aimed to investigate older adults' changes in access to care during the pandemic and their determinants. We used data from a cross-sectional study (LOST in Lombardia) conducted in autumn 2020 on a representative sample of 4400 older adults from the most populated region in Italy. Lifestyles, mental health, and access to healthcare services before and during the pandemic were collected. To identify factors associated with care delays, reduction in emergency department (ED) access, and hospitalisations, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) using multivariable log-binomial regression models. During the pandemic, compared to the year before, 21.5% of the study population increased telephone contacts with the general practitioner (GP) and 9.6% increased self-pay visits, while 22.4% decreased GP visits, 12.3% decreased outpatient visits, 9.1% decreased diagnostic exams, 7.5% decreased ED access, and 6% decreased hospitalisations. The prevalence of care delays due to patient's decision (overall 23.8%) was higher among men (PR 1.16, 95% CI 1.05-1.29), subjects aged 75 years or more (PR 1.12, 95% CI 1.00-1.25), and those with a higher economic status (p for trend &lt; 0.001). Participants with comorbidities more frequently cancelled visits and reduced ED access or hospitalisations, while individuals with worsened mental health status reported a higher prevalence of care delays and ED access reductions. Access to care decreased in selected sub-groups of older adults during the pandemic with likely negative impacts on mortality and morbidity in the short and long run

A spatial multi-scale fluorescence microscopy toolbox discloses entry checkpoints of SARS-CoV-2 variants in Vero E6 cells

: We exploited a multi-scale microscopy imaging toolbox to address some major issues related to SARS-CoV-2 interactions with host cells. Our approach harnesses both conventional and super-resolution fluorescence microscopy and easily matches the spatial scale of single-virus/cell checkpoints. After its validation through the characterization of infected cells and virus morphology, we leveraged this toolbox to reveal subtle issues related to the entry phase of SARS-CoV-2 variants in Vero E6 cells. Our results show that in Vero E6 cells the B.1.1.7 strain (aka Alpha Variant of Concern) is associated with much faster kinetics of endocytic uptake compared to its ancestor B.1.177. Given the cell-entry scenario dominated by the endosomal "late pathway", the faster internalization of B.1.1.7 could be directly related to the N501Y mutation in the S protein, which is known to strengthen the binding of Spike receptor binding domain with ACE2. Remarkably, we also directly observed the central role of clathrin as a mediator of endocytosis in the late pathway of entry. In keeping with the clathrin-mediated endocytosis, we highlighted the non-raft membrane localization of ACE2. Overall, we believe that our fluorescence microscopy-based approach represents a fertile strategy to investigate the molecular features of SARS-CoV-2 interactions with cells

A transcriptional sketch of a primary human breast cancer by 454 deep sequencing

Background: The cancer transcriptome is difficult to explore due to the heterogeneity of quantitative and qualitative changes in gene expression linked to the disease status. An increasing number of "unconventional" transcripts, such as novel isoforms, non-coding RNAs, somatic gene fusions and deletions have been associated with the tumoral state. Massively parallel sequencing techniques provide a framework for exploring the transcriptional complexity inherent to cancer with a limited laboratory and financial effort. We developed a deep sequencing and bioinformatics analysis protocol to investigate the molecular composition of a breast cancer poly(A)+ transcriptome. This method utilizes a cDNA library normalization step to diminish the representation of highly expressed transcripts and biology-oriented bioinformatic analyses to facilitate detection of rare and novel transcripts. Results: We analyzed over 132,000 Roche 454 high-confidence deep sequencing reads from a primary human lobular breast cancer tissue specimen, and detected a range of unusual transcriptional events that were subsequently validated by RT-PCR in additional eight primary human breast cancer samples. We identified and validated one deletion, two novel ncRNAs (one intergenic and one intragenic), ten previously unknown or rare transcript isoforms and a novel gene fusion specific to a single primary tissue sample. We also explored the non-protein-coding portion of the breast cancer transcriptome, identifying thousands of novel non-coding transcripts and more than three hundred reads corresponding to the non-coding RNA MALAT1, which is highly expressed in many human carcinomas. Conclusion: Our results demonstrate that combining 454 deep sequencing with a normalization step and careful bioinformatic analysis facilitates the discovery and quantification of rare transcripts or ncRNAs, and can be used as a qualitative tool to characterize transcriptome complexity, revealing many hitherto unknown transcripts, splice isoforms, gene fusion events and ncRNAs, even at a relatively low sequence sampling

A real world analysis of COVID-19 impact on hospitalizations in older adults with chronic conditions from an Italian region

Healthcare delivery reorganization during the COVID-19 emergency may have had a significant impact on access to care for older adults with chronic conditions. We investigated such impact among all adults with chronic conditions aged >= 65 years, identified through the electronic health databases of two local health agencies-ATS Brianza and ATS Bergamo-from the Lombardy region, Italy. We considered hospitalizations for 2020 compared to the average 2017-2019 and quantified differences using rate ratios (RRs). Overall, in 2017-2019 there were a mean of 374,855 older adults with >= 1 chronic condition per year in the two ATS and 405,371 in 2020. Hospitalizations significantly decreased from 84,624 (225.8/1000) in 2017-2019 to 78,345 (193.3/1000) in 2020 (RR 0.86). Declines were reported in individuals with many chronic conditions and for most Major Diagnostic Categories, except for diseases of the respiratory system. The strongest reductions were observed in hospitalizations for individuals with active tumours, particularly for surgical ones. Hospitalization rates increased in individuals with diabetes, likely due to COVID-19-related diseases. Although determinants of the decrease in demand and supply for care among chronic older adults are to be further explored, this raises awareness on their impacts on chronic patients' health in the medium and long run