Histological Evidence of Pulmonary Microthrombosis and Vasculitis in Life-Threatening Respiratory Virus Diseases.
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ABSTRACT:
SUBMITTER: Dolby HW
PROVIDER: S-EPMC7798721 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Respiratory syncytial virus (RSV) is often the first clinically relevant pathogen encountered in life, with nearly all children infected by two years of age. Many studies have also linked early-life severe respiratory viral infection with more pathogenic immune responses later in life that lead to pulmonary diseases like childhood asthma. This phenomenon is thought to occur through long-term immune system alterations following early-life respiratory viral infection and may include local responses such as unresolved inflammation and/or direct structural or developmental modifications within the lung. Furthermore, systemic responses that could impact the bone marrow progenitors may be a significant cause of long-term alterations, through inflammatory mediators and shifts in metabolic profiles. Among these alterations may be changes in transcriptional and epigenetic programs that drive persistent modifications throughout life, leaving the immune system poised toward pathogenic responses upon secondary insult. This review will focus on early-life severe RSV infection and long-term alterations. Understanding these mechanisms will not only lead to better treatment options to limit initial RSV infection severity but also protect against the development of childhood asthma linked to severe respiratory viral infections.
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Project description:Abstract Background Differential expression of selected immunity genes may have a role in susceptibility to Respiratory Syncytial Virus (RSV). There are few data about some candidate gene single nucleotide polymorphisms (SNPs) associated with the severity of respiratory infections (e.g., Toll-like receptor 4 [TLR4], Toll-like receptor 8 [TLR8], macrophage receptor with colagenous structure [MARCO], myxovirus resistance 1 [MX1]). The aims of this study were to detect the presence of SNPs in selected genes of previously healthy infants infected with RSV, to assess viral load (VL) and to analyze their relationship with life-threatening disease (LTD) Methods Prospective cohort study including previously healthy full-term infants < 12 months, hospitalized with a first RSV infection during 2017–2018. RSV diagnosis, virus quantification and genotyping for SNPs (TLR4 rs4986790, TLR4 rs4986791, MARCO rs1318645, MX1 rs469390, TLR8 rs3761624) were performed by qRT–PCR in nasopharyngeal aspirates obtained on admission. Patients with LTD were those admitted to the intensive care unit needing mechanical or non invasive ventilation Results 75 patients, mean age 3.9 months (±2.8), 41 (54.7%) male. Fifteen developed LTD. Infants who were homozygous (−/−) or heterozygous (+/−) for MX1rs469390 and TLR8rs3761624 or MARCOrs1318645 and TLR8rs3761624 had significantly more risk of developing LTD (OR 3.45, P = 0.042; OR 3.63, P = 0.048, respectively). Multivariable logistic regression analysis showed that concurrent MARCOrs1318645, MX1rs469390 and TLR8rs3761624 SNPs increased the risk of LTD (aOR 4.7, P = 0.018), fig 1. These SNPs also associated with prolonged length of stay (LOS) (P = 0.026) and > 7 days of hypoxemia (P = 0.031). No differences were seen in VL of patients with LTD compared with those with better outcome (P = 0.737). No differences in VL were seen in patients with SNPs. VL did not correlate with LOS or days of hypoxemia. No other socioeconomic, pregnancy or infant variables associated with LTD Conclusion To the best of our knowledge, this is the first study assessing the presence of concurrent SNPs and their association with life-threatening disease in previously healthy infants with RSV infection. These findings provide evidence on the importance of the host and its immune response for the severity of RSV infection. Disclosures All authors: No reported disclosures.
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Project description:Systemic vasculitides frequently affect the pulmonary vasculature. As the signs and symptoms of pulmonary vasculitis are variable and nonspecific, diagnosis and treatment represent a real challenge. Vasculitides should be given consideration, as these diseases present severe manifestations of rapidly progressing pulmonary disease. Examining other organs usually affected by vasculitides (e.g., the skin and kidneys) and determining autoantibody levels are essential to a better management of the disease. A radiological study would also contribute to establishing a diagnosis. The lungs are commonly involved in small-vessel vasculitis, anti-glomerular basement membrane disease, and vasculitides associated with antineutrophil cytoplasmic antibodies. Associated life-threatening diffuse alveolar haemorrhages and irreversible damage to other organs-usually the kidneys-are severe complications that require early diagnosis. Vasculitides are rare diseases that affect multiple organs. An increasing number of treatments-including biological agent-based therapies-requiring cooperation between specialists and centers have become available in the recent years. In the same way, clinicians should be familiar with the complications associated with immunosuppressive therapies.
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Project description:Numerous studies have demonstrated sex differences in drug reactions to the same drug treatment, steering away from the traditional view of one-size-fits-all medicine. A premise of this study is that the sex of a patient influences difference in disease characteristics and risk factors. In this study, we intend to exploit and to obtain better sex-specific biomarkers from gene-expression data. We propose a procedure to isolate a set of important genes as sex-specific genomic biomarkers, which may enable more effective patient treatment. A set of sex-specific genes is obtained by a variable importance ranking using a combination of cross-validation methods. The proposed procedure is applied to three gene-expression datasets.
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Project description:BackgroundDespite quick implementation of reperfusion therapies, a few patients with high-risk, acute, massive, pulmonary embolism (PE) remain highly hemodynamically unstable. Others have absolute contraindication to receive reperfusion therapies. Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) might lower their right ventricular overload, improve hemodynamic status, and restore tissue oxygenation.MethodsECMO-related complications and 90-day mortality were analyzed for 17 highly unstable, ECMO-treated, massive PE patients admitted to a tertiary-care center (2006-2015). Hospital- discharge survivors were assessed for long-term health-related quality of life. A systematic review of this topic was also conducted.ResultsSeventeen high-risk PE patients [median age 51 (range 18-70) years, Simplified Acute Physiology Score II (SAPS II) 78 (45-95)] were placed on VA-ECMO for 4 (1-12) days. Among 15 (82%) patients with pre-ECMO cardiac arrest, seven (41%) were cannulated during cardiopulmonary resuscitation, and eight (47%) underwent pre-ECMO thrombolysis. Pre-ECMO median blood pressure, pH, and blood lactate were, respectively: 42 (0-106) mmHg, 6.99 (6.54-7.37) and 13 (4-19) mmol/L. Ninety-day survival was 47%. Fifteen (88%) patients suffered in-ICU severe hemorrhages with no impact on survival. Like other ECMO-treated patients, ours reported limitations of all physical domains but preserved mental health 19 (4-69) months post-ICU discharge.ConclusionsVA-ECMO could be a lifesaving rescue therapy for patients with high-risk, acute, massive PE when thrombolytic therapy fails or the patient is too sick to benefit from surgical thrombectomy. Because heparin-induced clot dissolution and spontaneous fibrinolysis allows ECMO weaning within several days, future studies should investigate whether VA-ECMO should be the sole therapy or completed by additional mechanical clot-removal therapies in this setting.
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Project description:We characterized posttravel hospitalizations of citizens returning to Israel by summarizing the returning traveler hospitalization dataset of the national referral Center for Travel Medicine and Tropical Diseases at Sheba Medical Center in Israel. Of 722 hospitalizations, 181 (25%) infections were life-threatening; most would have been preventable by chemoprophylaxis and pretravel vaccination.
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Project description:Extracorporeal membrane oxygenation (ECMO) implantation for neonates with severe cardiorespiratory life-threatening conditions is highly effective. However, since ECMO is a high-risk and complex therapy, this treatment is usually performed in centers with proven expertise. A retrospective review of neonates, from January 2014 to January 2020, presenting with life-threatening conditions and treated by means of Hub and Spoke (HandS) ECMO in peripheral (spoke) hospitals. Data were retrieved from our internal ECMO registry. Protocols and checklists were revised and shared with all spoke hospitals located in North-Eastern Italy. Eleven neonates receiving maximal respiratory and cardiovascular support at a spoke hospital underwent HandS ECMO management. All but three patients were affected by life-threatening meconium aspiration syndrome (MAS). The median ECMO support duration and hospitalization were four (range 2-32) and 30 days (range 8-50), respectively. All but two patients (with congenital diaphragmatic hernia), were weaned off ECMO and discharged home. At a mean follow up of 33.7 ± 29.2 months, all survivors were alive and well, without medications, and normal somatic growth. All but one had normal neuropsychological development. HandS ECMO model for neonates with life-threatening conditions is effective and successful. A specialized multidisciplinary team and close cooperation between Hub and Spoke centers are essential for success.
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Project description:BackgroundThis is an update of the section on complications that are associated with coughing in the 2006 CHEST cough guidelines that addresses two aims: (1) to systematically identify and thematically categorize the diverse complications of cough by providing a guide for future studies and (2) to identify gaps in the literature for future research.Research questionWhat are the potential complications that are associated with the act of coughing that have been reported in infants, children, adolescents, and adults?Study design and methodsA scoping review was performed with the use of PubMed and SCOPUS databases that were searched from their beginning until September 6, 2019.ResultsTwo hundred forty-seven publications met our inclusion criteria. To these, we added 38 articles from the 2006 complications paper that were not identified in the literature search plus the paper itself for a final total of 286 publications that formed the basis of this review. Since 2006, three new categories of complications have been reported: ear, nose and throat; disease transmission; and laboratory testing. Multiple additional complications that fall outside of these three categories have also been identified and included in the following categories: cardiovascular, constitutional symptoms, dermatologic, GI, genitourinary, musculoskeletal, neurologic, ophthalmologic, psychosocial/quality of life, and respiratory. Not previously highlighted is that some of the complications led to serious morbidity that included death, especially in patients with comorbid conditions, and potentially resulted in harm to others when cough resulted in a motor vehicle accident.InterpretationOur work identified a large number of cough complications that we thematically categorized primarily by organ system so that future studies of each system or each complication can be conducted. The gap in the literature that future studies should address is to identify the frequency of the complications and the strength of their association with cough. Only then will one be able to describe the findings in a manner that allows specific recommendations for avoiding these complications. In the meantime, patients with cough should be evaluated and treated according to evidence-based guidelines to mitigate or prevent the myriad of potential complications that are associated with coughing.
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Project description: Not available
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