Summary: Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Two main functions have been attributed to exosomes: their capacity to transport proteins, lipids and nucleic acids between cells and organs, as well as their potential to act as natural intercellular communicators in normal biological processes and in pathologies. From a clinical perspective, the majority of applications use exosomes as biomarkers of disease. A new approach uses exosomes as biologically active carriers to provide a platform for the enhanced delivery of cargo in vivo. One of the major limitations in developing exosome-based therapies is the difficulty of producing sufficient amounts of safe and efficient exosomes. The identification of potential proteins involved in exosome biogenesis is expected to directly cause a deliberate increase in exosome production. In this review, we summarize the current state of knowledge regarding exosomes, with particular emphasis on their structural features, biosynthesis pathways, production techniques and potential clinical applications. Full article

Background: In polytrauma (PT) patients, osseous thoracic injuries are commonly observed. One of the most severe injuries is the flail chest where the rib cage is broken in such a way that leads to a partial functional detachment of the thoracic wall. Especially in PT patients, the integrity of the respiratory system and especially, of the respiratory muscles is essential to prevent respiratory failure. Besides conservative treatment options, flail chest injuries may be surgically stabilized. However, this treatment option is rarely carried out and evidence on the outcome of surgically treated flail chest patients is rare. Objective: This study intends to investigate the clinical outcome of PT patients with the diagnosis of a flail chest who received an osteosynthetic stabilization for that compared to the same group of patients without an operative treatment. The between-groups outcome was compared regarding the duration of the total hospital and the intensive care unit (ICU) stay, the total of the invasive ventilation days, the incidence of pneumonia, and the dosage of the pain medication at the hospital discharge. Methods: A retrospective analysis was conducted including all PT patients who received an osteosynthetic stabilization of a flail chest. Furthermore, another cohort of PT patients and the diagnosis of a flail chest but without operative treatment was determined. Both groups were case-control matched for the Injury Severity Score (ISS) and age. Further statistical analysis was performed using the Wilcoxon signed-rank test and the McNemar’s test. Results: Out of eleven operatively and 59 conservatively treated patients, eleven patients per group were matched. Further analysis revealed no significant differences in the normal ward treatment duration (5.64 ± 6.62 and 6.20 ± 5.85 days), the invasive ventilation duration (was 6.25 ± 7.17 and 7.10 ± 6.14 days), the morphine equivalent dosage of the oral analgesia (61.36 ± 67.23 mg and 39.67 ± 65.65 mg), and the pneumonia incidence (36.4 and 54.5%) when conservatively and operatively treated patients were compared, respectively. However, surgically treated patients had a longer ICU (25.18 ± 14.48 and 15.27 ± 12.10 days, Z = −2.308, p = 0.021) and a longer total hospital treatment duration (30.10 ± 13.01 and 20.91 ± 10.34 days, Z = −2.807, p = 0.005) when compared to conservatively treated patients. Conclusion: In the present study cohort, there was no outcome difference between conservatively and operatively treated patients with the diagnosis of a flail chest regarding the normal ward treatment duration, the invasive ventilation duration, the morphine equivalent dosage of the oral analgesia, and the pneumonia incidence while ICU treatment duration and hospital treatment duration was longer in operatively treated patients. Full article

Obstructive sleep apnoea (OSA) is associated with several diseases related to metabolic and cardiovascular risk. Although the mechanisms involved in the development of these disorders may vary, OSA patients frequently present an increase in transforming growth factor beta (TGFβ), the activity of which is higher still in patients with hypertension, diabetes or cardiovascular morbidity. Smad4 is a member of the small mother against decapentaplegic homologue (Smad) family of signal transducers and acts as a central mediator of TGFβ signalling pathways. In this study, we evaluate Smad4 protein and mRNA expression from 52 newly diagnosed OSA patients, with an apnoea–hypopnoea index (AHI) ≥30 and 26 healthy volunteers. These analyses reveal that OSA patients exhibit high levels of SMAD4 which correlates with variation in HIF1α, mTOR and circadian genes. Moreover, we associated high concentrations of Smad4 plasma protein with the presence of diabetes, dyslipidaemia and hypertension in these patients. Results suggest that increased levels of SMAD4, mediated by intermittent hypoxaemia and circadian rhythm deregulation, may be associated with cardiometabolic comorbidities in patients with sleep apnoea. Full article

(1) Background: The benefit of acute ischemic stroke (AIS) treatment declines with any time delay until treatment. Hence, factors influencing the time from symptom onset to admission (TTA) are of utmost importance. This study aimed to assess temporal trends and risk factors for delays in TTA. (2) Methods: We included 1244 consecutive patients from 2015 to 2018 with suspected stroke presenting within 24 h after symptom onset registered in our prospective, pre-specified hospital database. Temporal trends were assessed by comparing with a cohort of a previous study in 2006. Factors associated with TTA were assessed by univariable and multivariable regression analysis. (3) Results: In 1244 patients (median [IQR] age 73 [60–82] years; 44% women), the median TTA was 96 min (IQR 66–164). The prehospital time delay reduced by 27% in the last 12 years and the rate of patients referred by Emergency medical services (EMS) increased from 17% to 51% and the TTA for admissions by General Practitioner (GP) declined from 244 to 207 min. Factors associated with a delay in TTA were stroke severity (beta−1.9; 95% CI–3.6 to −0.2 min per point NIHSS score), referral by General Practitioner (GP, beta +140 min, 95% CI 100–179), self-admission (+92 min, 95% CI 57–128) as compared to admission by emergency medical services (EMS) and symptom onset during nighttime (+57 min, 95% CI 30–85). Conclusions: Although TTA improved markedly since 2006, our data indicates that continuous efforts are mandatory to raise public awareness on the importance of fast hospital referral in patients with suspected stroke by directly informing EMS, avoiding contact of a GP, and maintaining high effort for fast transportation also in patients with milder symptoms. Full article

This study investigates the effects of sex, education, and country of birth on clinical presentations and outcomes of interdisciplinary multimodal pain rehabilitation programs (IMMRPs). A multivariate improvement score (MIS) and two retrospective estimations of changes in pain and ability to handle life situations were used as the three overall outcomes of IMMRPs. The study population consisted of chronic pain patients within specialist care in the Swedish Quality Registry for Pain Rehabilitation (SQRP) between 2008 and 2016 at baseline (n = 39,916), and for the subset participating in IMMRPs (n = 14,666). A cluster analysis based on sex, education, and country of origin revealed significant differences in the following aspects: best baseline clinical situation was for European women with university educations and the worst baseline clinical situation was for all patients born outside Europe of both sexes and different educations (i.e., moderate-large effect sizes). In addition, European women with university educations also had the most favorable overall outcomes in response to IMMRPs (small effect sizes). These results raise important questions concerning fairness and equality and need to be considered when optimizing assessments and content and delivery of IMMRPs for patients with chronic pain. Full article

Bacterial infections are the main cause of patient morbidity and mortality worldwide. Diagnosis can be difficult and delayed as well as the identification of the etiological pathogen, necessary for a tailored antibiotic therapy. Several non-invasive diagnostic procedures are available, all with pros and cons. Molecular nuclear medicine has highly contributed in this field by proposing several different radiopharmaceuticals (antimicrobial peptides, leukocytes, cytokines, antibiotics, sugars, etc.) but none proved to be highly specific for bacteria, although many agents in development look promising. Indeed, factors including the number and strain of bacteria, the infection site, and the host condition, may affect the specificity of the tested radiopharmaceuticals. At the Third European Congress on Infection/Inflammation Imaging, a round table discussion was dedicated to debate the pros and cons of different radiopharmaceuticals for imaging bacteria with the final goal to find a consensus on the most relevant research steps that should be fulfilled when testing a new probe, based on experience and cumulative published evidence. Full article

Pediatric myopia has become a major international public health concern. The prevalence of myopia has undergone a significant increase worldwide. The purpose of this review of the current literature was to evaluate the peer-reviewed scientific literature on the efficacy and safety of low-dose atropine treatment combined with overnight orthokeratology for myopia control. A search was conducted in Pubmed and Web of Science with the following search strategy: (atropine OR low-dose atropine OR 0.01% atropine) AND (orthokeratology OR ortho-k) AND (myopia control OR myopia progression). All included studies improved myopia control by the synergistic effect of orthokeratology with low-dose atropine, compared with orthokeratology treatment alone. All studies included a short or medium follow-up period; therefore longer-term studies are necessary to validate these results. Full article

Hip fracture (HF) in older patients is associated with a high six-month mortality rate. Several clinical conditions may affect outcome, including baseline characteristics, co-existing acute illnesses, perioperative factors, and postoperative complications. Our primary objective was to estimate the respective effect of these four domains on six-month mortality after HF. A retrospective observational study using a monocentric cohort of older patients was conducted. All patients ≥ 70 years old admitted to the emergency department for HF and hospitalized in our perioperative geriatric care unit from June 2009 to September 2018 were included. Among 1015 included patients, five (0.5%) were lost to follow-up, and 1010 were retained in the final analysis (mean age 86 ± 6 years). The six-month mortality rate was 14.8%. The six-month attributable mortality estimates were as follows: baseline characteristics (including age, gender, comorbidities, autonomy, type of fracture): 62.4%; co-existing acute illnesses (including acute events present before surgery that could result from the fracture or cause it): 0% (not significantly associated with six-month mortality); perioperative factors (including blood transfusion and delayed surgery): 12.3%; severe postoperative complications: 11.9%. Baseline characteristics explained less than two-thirds of the six-month mortality after HF. Optimizing patients care by improving management of perioperative factors and thus decreasing postoperative complications, could reduce by a maximum of one quarter of the six-month mortality rate after HF. Full article

Background: Comparative data of SARS-CoV-2 IgM/IgG serology rapid diagnostic tests (RDTs) is scarce. We thus performed a head-to-head comparison of three RDTs. Methods: In this unmatched case-control study, blood samples from 41 RT-PCR-confirmed COVID-19 cases and 50 negative controls were studied. The diagnostic accuracy of three commercially available COVID-19 RDTs: NTBIO (RDT-A), Orient-Gene (RDT-B), and MEDsan (RDT-C), against both a recombinant spike-expressing immunofluorescence assay (rIFA) and Euroimmun IgG ELISA, was assessed. RDT results concordant with the reference methods, and between whole blood and plasma, were established by the Kendall coefficient. Results: COVID-19 cases’ median time from RT-PCR to serology was 22 days (interquartile range (IQR) 13–31 days). Whole-blood IgG detection with RDT-A, -B, and -C showed 0.93, 0.83, and 0.98 concordance with rIFA. Against rIFA, RDT-A sensitivity (SN) was 92% (95% CI: 78–98) and specificity (SP) 100% (95% CI: 91–100), RDT-B showed 87% SN (95% CI: 72–95) and 98% SP (95% CI: 88–100), and RDT-C 100% SN (95% CI: 88–100) and 98% SP (95% CI: 88–100). Against ELISA, SN and SP were above 90% for all three RDTs. Conclusions: RDT-A and RDT-C displayed IgG detection SN and SP above 90% in whole blood. These RDTs could be considered in the absence of routine diagnostic serology facilities. Full article

Background: It is essential to study the effect of potential co-factors on the risk of death in patients infected by COVID-19. The identification of risk factors is important to allow more efficient public health and health services strategic interventions with a significant impact on deaths by COVID-19. This study aimed to identify factors associated with COVID-19 deaths in Portugal. Methods: A national dataset with the first 20,293 patients infected with COVID-19 between 1 January and 21 April 2020 was analyzed. The primary outcome measure was mortality by COVID-19, measured (registered and confirmed) by Medical Doctors serving as health delegates on the daily death registry. A logistic regression model using a generalized linear model was used for estimating Odds Ratio (OR) with 95% confidence intervals (95% CI) for each potential risk indicator. Results: A total of 502 infected patients died of COVID-19. The risk factors for increased odds of death by COVID-19 were: sex (male: OR = 1.47, ref = female), age ((56–60) years, OR = 6.01; (61–65) years, OR = 10.5; (66–70) years, OR = 20.4; (71–75) years, OR = 34; (76–80) years, OR = 50.9; (81–85) years, OR = 70.7; (86–90) years, OR = 83.2; (91–95) years, OR = 91.8; (96–104) years, OR = 140.2, ref = (0–55)), Cardiac disease (OR = 2.86), Kidney disorder (OR = 2.95), and Neuromuscular disorder (OR = 1.58), while condition (None (absence of precondition); OR = 0.49) was associated with a reduced chance of dying after adjusting for other variables of interest. Conclusions: Besides age and sex, preconditions justify the risk difference in mortality by COVID-19. Full article

Background: The risk, correlates, and consequences of incident atrial fibrillation (AF) in patients with chronic coronary artery disease (CAD) are largely unknown. Methods and results: We analyzed incident AF during a 3-year follow-up in 5031 CAD outpatients included in the prospective multicenter CARDIONOR registry and with no history of AF at baseline. Incident AF occurred in 266 patients (3-year cumulative incidence: 4.7% (95% confidence interval (CI): 4.1 to 5.3)). Incident AF was diagnosed during cardiology outpatient visits in 177 (66.5%) patients, 87 of whom were asymptomatic. Of note, 46 (17.3%) patients were diagnosed at time of hospitalization for heart failure, and a few patients (n = 5) at the time of ischemic stroke. Five variables were independently associated with incident AF: older age (p < 0.0001), heart failure (p = 0.003), lower left ventricle ejection fraction (p = 0.008), history of hypertension (p = 0.010), and diabetes mellitus (p = 0.033). Anticoagulant therapy was used in 245 (92%) patients and was associated with an antiplatelet drug in half (n = 122). Incident AF was a powerful predictor of all-cause (adjusted hazard ratio: 2.04; 95% CI: 1.47 to 2.83; p < 0.0001) and cardiovascular mortality (adjusted hazard ratio: 2.88; 95% CI: 1.88 to 4.43; p < 0.0001). Conclusions: In CAD outpatients, real-life incident AF occurs at a stable rate of 1.6% annually and is frequently diagnosed in asymptomatic patients during cardiology outpatient visits. Anticoagulation is used in most cases, often combined with antiplatelet therapy. Incident AF is associated with increased mortality. Full article

Background: Helicobacter pylori and intestinal parasites are estimated to infect with high burden worldwide. However, their concomitant infections are poorly determined in industrialized countries, such as Italy. In this study we aim at describing the presence of H. pylori as well as the proportion of coinfections with intestinal parasites among subjects who attended a referral center for tropical diseases in Northern Italy. Methods: This was a case-control study. Screening for H. pylori and parasites was performed on stool samples of 93 adults from different geographical origin (Africa, Asia, South-America, East-Europe and Italy). H. pylori infection was examined by CLIA and its cagA positivity was determined by rtPCR. Intestinal parasites (i.e., protozoa and helminths) were examined by microscopy and rtPCR. Results: Sixty-one out of 93 patients (66%) were positive to H. pylori and 31 (33%) were cagA+. Among H. pylori positives, 45 (74%) had a concomitant infection. The coinfection H. pylori–Blastocystis was the most frequent one, followed by H. pylori–E. coli. Multivariable logistic regression showed that positivity to H. pylori was associated with having a coinfection. Conclusion: Our data suggested that H. pylori and intestinal parasitic infections are fairly common in subjects who attended a referral center for tropical diseases in Northern Italy. The high rate of H. pylori infection, and especially the positivity to the virulent cagA+, should be taken into consideration in subjects undergoing screening for parasitic infections. Full article