Background
The effect of chronic use of renin–angiotensin–aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19 related outcomes in hypertensive patients.
Methods
A single center study was conducted on 133 consecutive hypertensive subjects presenting to the Emergency Department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9th and 31st March 2020.
Results
All patients were grouped according to their chronic antihypertensive medications (ACEIs, N=40; ARBs, N=42; not on RAAS inhibitors, N=51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy and need for non-invasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared to the non-RAAS population (odds ratio [OR] 0.25, CI95% 0.09-0.66 p=0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI95% 0.17-1.83, p=0.341).
Conclusions
Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID 19-related morbidity and mortality.
Immunoglobulin (Ig) replacement therapy dramatically changed the clinical course of primary hypogammaglobulinemias, significantly reducing the incidence of infectious events. Over the last two decades its use has been extended to secondary antibody deficiencies, particularly those related to hematological disorders as lymphoproliferative diseases (LPDs) and multiple myeloma. In these malignancies, hypogammaglobulinemia can be an intrinsic aspect of the disease or follow chemo-immunotherapy regimens, including anti-CD20 treatment. Other than in LPDs the broadening use of immunotherapy (e.g., rituximab) and immune-suppressive therapy (steroids, sulfasalazine, and mycophenolate mofetil) has extended the occurrence of iatrogenic hypogammaglobulinemia. In particular, in both autoimmune diseases and solid organ transplantation Ig replacement therapy has been shown to reduce the rate of infectious events. Here, we review the existing literature about Ig replacement therapy in secondary hypogammaglobulinemia, with special regard for subcutaneous administration route, a safe, effective, and well-tolerated treatment approach, currently well established in primary immunodeficiencies and secondary hypogammaglobulinemias.
In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.
An increased prevalence of malignant lymphoma and of gastric cancer has been observed in large cohorts of patients with common variable immunodeficiency (CVID), the most frequently symptomatic primary immunodeficiency. Surveillance strategies for cancers in CVID should be defined based on epidemiological data. Risks and mortality for cancers among 455 Italian patients with CVID were compared to cancer incidence data from the Italian Cancer Registry database. CVID patients showed an increased cancer incidence for all sites combined (Obs = 133, SIR = 2.4; 95%CI = 1.7–3.5), due to an excess of non-Hodgkin lymphoma (Obs = 33, SIR = 14.3; 95%CI = 8.4–22.6) and of gastric cancer (Obs = 25; SIR = 6.4; 95%CI = 3.2–12.5). CVID patients with gastric cancer and lymphoma had a worse survival in comparison to cancer-free CVID (HR: 4.8, 95%CI: 4.2–44.4 and HR: 4.2, 95%CI: 2.8–44.4). Similar to what observed in other series, CVID-associated lymphomas were more likely to be of B cell origin and often occurred at extra-nodal sites. We collected the largest case-series of gastric cancers in CVID subjects. In contrast to other reports, gastric cancer was the leading cause of death in CVID. Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer. CVID developed gastric cancer 15 years earlier than the normative population, but they had a similar overall survival. Only CVID diagnosed at early stage gastric cancer survived >24 months. Stomach histology from upper endoscopy performed before cancer onset showed areas of atrophic gastritis, intestinal metaplasia or dysplasia. CVID patients might progress rapidly to an advanced cancer stage as shown by patients developing a III-IV stage gastric cancer within 1 year from an endoscopy without signs of dysplasia. Based on high rate of mortality due to gastric cancer in Italian CVID patients, we hereby suggest a strategy aimed at early diagnosis, based on regular upper endoscopy and on Helicobacter pylori infection treatment, recommending an implementation of national guidelines.
In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, fibroblast foci are considered small, distinct lesions, although they have been proposed to form a highly interconnected reticulum as the leading edge of a “wave” of fibrosis. Here, we characterized fibroblast focus morphology and interrelationships in 3D using an integrated micro-CT and histological methodology. In 3D, fibroblast foci were morphologically complex structures, with large variations in shape and volume (range, 1.3 × 104 to 9.9 × 107 μm3). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm3 of lung tissue to a maximum of 11.1 per mm3 of lung tissue. Each focus was an independent structure, and no interconnections were observed. Together, our data indicate that in 3D fibroblast foci form a constellation of heterogeneous structures with large variations in shape and volume, suggesting previously unrecognized plasticity. No evidence of interconnectivity was identified, consistent with the concept that foci represent discrete sites of lung injury and repair.
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