Obstructive sleep apnea (OSA) is now recognized as an independent and important risk factor for cardiovascular diseases such as hypertension, coronary heart disease, heart failure and stroke. ...Clinical and experimental data have confirmed that intermittent hypoxia is a major contributor to these deleterious consequences. The repetitive occurrence of hypoxia-reoxygenation sequences generates significant amounts of free radicals, particularly in moderate to severe OSA patients. Moreover, in addition to hypoxia, reactive oxygen species (ROS) are potential inducers of the hypoxia inducible transcription factor-1 (HIF-1) that promotes the transcription of numerous adaptive genes some of which being deleterious for the cardiovascular system, such as the endothelin-1 gene. This review will focus on the involvement of the ROS-HIF-1-endothelin signaling pathway in OSA and intermittent hypoxia and discuss current and potential therapeutic approaches targeting this pathway to treat or prevent cardiovascular disease in moderate to severe OSA patients.
Patients with hematological malignancy and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatments impair humoral ...response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears as a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2. We report the effect of CCP in a cohort of 112 patients with hematological malignancy and COVID-19 and a propensity score analysis on subgroups of patients with B-cell lymphoid disease treated (n = 81) or not (n = 120) with CCP between May 1, 2020 and April 1, 2021. The overall survival of the whole cohort was 65% (95% CI = 56-74.9) and 77.5% (95% CI = 68.5-87.7) for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibody therapy was associated with better overall survival, whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20-exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI = 31-80) in the CCP-treated group compared to the CCP-untreated subgroup, confirmed in the other sensitivity analyses. Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response.
Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality, and apnea-induced intermittent hypoxia (IH) is known to promote various cardiovascular alterations such as vascular ...remodeling. However, the mechanisms that underlie IH remain incompletely investigated. We previously demonstrated that the hypoxia-inducible factor-1 (HIF-1) and endothelin-1 (ET-1) are involved in arterial hypertension and myocardial susceptibility to infarction induced by IH. Thus the objective of the present study was to investigate whether both ET-1 and HIF-1 were also involved in the vascular inflammatory remodeling induced by IH. Mice partially deficient for the Hif1α gene (HIF-1α(+/-)) and their wild-type equivalents, as well as C57BL/6J mice, treated or not with bosentan, a dual endothelin receptor antagonist, were exposed to IH or normoxia for 2 wk, 8 h/day. Splenocyte proliferative and secretory capacities, aortic nuclear factor-κB (NF-κB) and HIF-1 activities, and expression of cytokines and intima-media thickness (IMT) were measured. IH induced a systemic and aortic inflammation characterized by an increase in splenocyte proliferative and secretory capacities, aortic NF-κB activity, and cytokine expression in the aortic wall. This was accompanied by an increase in IMT. These modifications were prevented in HIF-1α(+/-) and bosentan-treated mice. The results of this study suggest that ET-1 is a major contributor to the vascular inflammatory remodeling induced by OSA-related IH, probably through HIF-1-dependent activation of NF-κB.
is a challenge for clinicians due to increasing drug resistance and dwindling treatment options. We report on the activity of MEDI3902, an antibody targeting type 3 secretion protein PcrV and Psl ...exopolysaccharide, in rabbit bloodstream and lung infection models. MEDI3902 prophylaxis or treatment was protective in both acute models and exhibited enhanced activity when combined with a subtherapeutic dose of meropenem. These findings further support MEDI3902 for the prevention or treatment of serious
infections.
New drugs targeting antimicrobial resistant pathogens, including
, have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ...ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections.
We report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with
by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression.
In a rabbit model of non-ventilated pneumonia, endobronchial challenge with live
6206, but not with UV-killed Pa6206, caused acute respiratory distress syndrome, as evidenced by acute lung inflammation, pulmonary edema, hemorrhage, severe hypoxemia, hyperlactatemia, neutropenia, thrombocytopenia, and hypoglycemia, which preceded respiratory failure and death. Pa6206 increased >100-fold in the lungs and then disseminated from there to infect distal organs, including spleen and kidneys. At 5 h post-infection, 67% of Pa6206-challenged rabbits had PaO
<60 mmHg, corresponding to a clinical cut-off when oxygen therapy would be required. When administered at 5 h post-infection, humanized dosing regimens of tobramycin and meropenem reduced mortality to 17-33%, compared to 100% for saline-treated rabbits (
<0.001 by log-rank tests). For meropenem which exhibits time-dependent bactericidal activity, rabbits treated with a humanized meropenem dosing regimen of 80 mg/kg q2h for 24 h achieved 100% T>MIC, resulting in 75% microbiological clearance rate of Pa6206 from the lungs. For tobramycin which exhibits concentration-dependent killing, rabbits treated with a humanized tobramycin dosing regimen of 8 mg/kg q8h for 24 h achieved C
/MIC of 9.8 ± 1.4 at 60 min post-dose, resulting in 50% lung microbiological clearance rate. In contrast, rabbits treated with a single tobramycin dose of 2.5 mg/kg had C
/MIC of 7.8 ± 0.8 and 8% (1/12) microbiological clearance rate, indicating that this rabbit model can detect dose-response effects.
The rabbit model may be used to help predict clinical efficacy of new antibacterial drugs for the treatment of non-ventilated
pneumonia.
Le diagnostic microbiologique de certaines maladies infectieuses reste actuellement un défi. Les nouvelles approches en biologie moléculaire sont prometteuses pour nombre de situations. Si les ...réactions de polymérisation en chaîne (PCR) multiplex, que ce soit dans le liquide cérébro-spinal (LCS) ou sur prélèvements respiratoires, ont montré une réduction de la durée d’antibiothérapie et de la durée d’hospitalisation, elles n’ont pas montré d’impact sur la mortalité. De plus, ces PCR multiplex, tout comme le panel Infections sexuellement transmissibles (IST), recherchent tous les pathogènes ou presque pouvant être incriminés dans les méningites et méningo-encéphalites ou pneumonies ou IST, et ne tiennent pas compte de l’orientation clinique adaptée au patient. La métagénomique clinique, encore peu accessible à large échelle actuellement, apparaît intéressante pour le diagnostic microbiologique avec le potentiel d’intégrer des données de l’hôte dans l’équation diagnostic- traitement, permettant ainsi une prise en charge personnalisée du patient atteint de maladie infectieuse.
Microbiological diagnostic of numerous infectious diseases remains a challenge to this date. New molecular biology strategies are promising. If multiplex polymerase chain reaction (PCR) used for meningitis/meningo-encephalitis or respiratory syndroms showed a reduction in antibiotic duration and on hospital length of stay, they did not have an impact on mortality. Furthermore, such multiplex PCR’s, as the Sexually transmitted infection (STI) panel, screen for a majority of pathogens implicated in meningitis/meningo-encephalitis, pneumonia or STI, regardless of patient-based clinical orientation. Clinical metagenomic, which is not totally accessible in daily routine, appears interesting for microbiological diagnostic. With the potential integration of host data into the diagnostic-treatment equation, it offers a promising next step towards personalized patient care.
Artificial intelligence (AI) and machine learning (ML) have the potential to revolutionize the management of febrile neutropenia (FN) and drive progress toward personalized medicine.
In this review, ...we detail how the collection of a large number of high-quality data can be used to conduct precise mathematical studies with ML and AI. We explain the foundations of these techniques, covering the fundamentals of supervised and unsupervised learning, as well as the most important challenges, e.g. data quality, 'black box' model interpretation and overfitting. To conclude, we provide detailed examples of how AI and ML have been used to enhance predictions of chemotherapy-induced FN, detection of bloodstream infections (BSIs) and multidrug-resistant (MDR) bacteria, and anticipation of severe complications and mortality.
There is promising potential of implementing accurate AI and ML models whilst managing FN. However, their integration as viable clinical tools poses challenges, including technical and implementation barriers. Improving global accessibility, fostering interdisciplinary collaboration, and addressing ethical and security considerations are essential. By overcoming these challenges, we could transform personalized care for patients with FN.
The incidence of campylobacteriosis has substantially increased over the past decade, notably in France. Secondary localizations complicating invasive infections are poorly described. We aimed to ...describe vascular infection or endocarditis caused by Campylobacter spp. We included 57 patients from a nationwide 5-year retrospective study on Campylobacter spp. bacteremia conducted in France; 44 patients had vascular infections, 12 had endocarditis, and 1 had both conditions. Campylobacter fetus was the most frequently involved species (83%). Antibiotic treatment involved a β-lactam monotherapy (54%) or was combined with a fluoroquinolone or an aminoglycoside (44%). The mortality rate was 25%. Relapse occurred in 8% of cases and was associated with delayed initiation of an efficient antimicrobial therapy after the first symptoms, diabetes, and coexistence of an osteoarticular location. Cardiovascular Campylobacter spp. infections are associated with a high mortality rate. Systematically searching for those localizations in cases of C. fetus bacteremia may be warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Major bleedings have been described with cefazolin. The objective was to determine the frequency of bleeding events in cefazolin-treated patients and to identify risk factors for these ...complications.
Methods
Monocenter prospective observational study of all consecutive cefazolin-treated patients. Patients benefited from a daily clinical assessment of bleedings and a twice-a-week blood sampling including hemostasis. Bleedings were classified according to the International Society on Thrombosis and Hemostasis classification: major, clinically relevant non-major bleedings (CRNMB) and minor bleedings.
Results
From September 2019 to July 2020, 120 patients were included, with a mean age of 59.4 (± 20.7) years; 70% of them (84/120) were men. At least 1 CRNMB or major bleeding were observed in 10% of the patients (12/120). Compared to patients with no or minor bleeding, patients with CRNMB or major bleeding were, upon start of cefazolin, more frequently hospitalized in an intensive care unit (7/12, 58.3%, vs. 12/108, 11.1%,
P
< 0.001, respectively) and receiving vitamin K antagonists (4/12, 33.3%, vs. 8/108, 7.4%,
P
= 0.019, respectively). After multivariate analysis, patients receiving vitamin K antagonists the day prior bleeding and/or treated for endocarditis were factors associated with an increased risk of CRNMB or major bleeding (odd ratio 1.36, confidence interval 95%, 1.06–1.76,
P
= 0.020 and 1.30, 1.06–1.61,
P
= 0.015, respectively).
Conclusions
Bleeding events associated with cefazolin treatment are frequent. Close clinical monitoring should be performed for patients treated for endocarditis and/or receiving vitamin K antagonists. Hemostasis work-up could be restricted to these patients.
AimsTo assess the incidence density of local complications of peripheral venous catheters in patients aged 70 years and older, to identify risk factors for local complications of peripheral venous ...catheters, to describe microbiological epidemiology and to assess the impact of complications on patient outcomes.DesignProspective, observational, single‐centre study.MethodsPatients 70 years and older admitted to the geriatric department of a teaching hospital in France between December 2019 and May 2020 were considered for inclusion if they had a peripheral venous catheter during their stay. Nurses checked the catheter insertion site three times a day for local complications; physicians ensured the follow‐up of complications. The STROBE checklist was used in this prospective observational study.ResultsA total of 322 patients were included, with 849 peripheral venous catheters; the median age was 88 years and 182 (56.5%) were women. The incidence density of local complications was 50.5/1000 peripheral venous catheter‐days. Risk factors for local complications on multivariate analysis were dressing replacement (OR 1.18), furosemide (OR 1.11) and vancomycin (OR 1.60) infusion, urinary continence (OR 1.09) and hematoma at the catheter insertion site (OR 1.15). Thirteen cellulitis and three abscesses were diagnosed. Occurrence of a local complication was associated with a 3‐day increased duration of hospital stay (17 vs. 14 days).ConclusionRisk factors for peripheral venous catheter local complications include urinary continence, furosemide or vancomycin infusion, hematoma at the peripheral venous catheter insertion site or dressing replacement.Implication for the Patient CareCloser clinical monitoring may help reduce the occurrence of local peripheral venous catheters complication in patients 70 years and older.Relevance to Clinical PracticePatients at greater risk of peripheral venous catheter local complications deserve closer clinical monitoring or improved preventive measures, which may be beneficial to reduce the length of hospital stay.No Patient or Public ContributionThe study was designed to describe risk factors for local complications of peripheral venous catheters in order to reinforce surveillance in this specific population by nurses and medical staffs. Patients had their peripheral venous catheter insertion site checked thrice a day by the nurse in charge as part of usual care. They, as service users, caregivers or members of the public, were not solicited for data collection, analysis, interpretation or preparation of the manuscript.
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