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Antibiotics (Basel, Switzerland) Jun 2024Bloodstream infections (BSI) caused by multidrug-resistant (MDR) bacteria, pose a major threat for patients, especially for those who are immunosuppressed. Rapid...
Bloodstream infections (BSI) caused by multidrug-resistant (MDR) bacteria, pose a major threat for patients, especially for those who are immunosuppressed. Rapid pathogen detection and characterization from positive blood cultures are crucial in the management of patients with BSI to enable an adequate and timely antimicrobial therapy. This study aimed to investigate the potential role of the Molecular Mouse system, a new CE IVD molecular test designed to rapidly detect the causative agents of bacteremia and their resistance determinants, in the management of the therapy in critically ill patients. Agreement between the results of the Molecular Mouse and the conventional routine method was also considered. Overall, 100 positive blood cultures were collected from septic critically ill patients from May 2023 to January 2024 and analyzed with Molecular Mouse and routine protocols. The new instrument consistently agreed with the routine protocols in the case of monomicrobial blood cultures, while some discrepancies were obtained in the polymicrobial samples. Antimicrobial resistance genes were detected in 35 samples, with and CTX-M-1/9 groups being the most frequently detected targets. Therapy was adjusted in 42 critically ill patients confirming the importance of new rapid molecular tests in the management of positive blood cultures, to adjust empirical therapy and use new antibiotics accurately.
PubMed: 38927183
DOI: 10.3390/antibiotics13060517 -
Scientific Reports Jun 2024Idiopathic Pulmonary Fibrosis (IPF) is a debilitating and fatal lung disease characterized by the excessive formation of scar tissue and decline of lung function....
Idiopathic Pulmonary Fibrosis (IPF) is a debilitating and fatal lung disease characterized by the excessive formation of scar tissue and decline of lung function. Despite extensive research, only two FDA-approved drugs exist for IPF, with limited efficacy and relevant side effects. Thus, there is an urgent need for new effective therapies, whose discovery strongly relies on IPF animal models. Despite some limitations, the Bleomycin (BLM)-induced lung fibrosis mouse model is widely used for antifibrotic drug discovery and for investigating disease pathogenesis. The initial acute inflammation triggered by BLM instillation and the spontaneous fibrosis resolution that occurs after 3 weeks are the major drawbacks of this system. In the present study, we applied micro-CT technology to a longer-lasting, triple BLM administration fibrosis mouse model to define the best time-window for Nintedanib (NINT) treatment. Two different treatment regimens were examined, with a daily NINT administration from day 7 to 28 (NINT 7-28), and from day 14 to 28 (NINT 14-28). For the first time, we automatically derived both morphological and functional readouts from longitudinal micro-CT. NINT 14-28 showed significant effects on morphological parameters after just 1 week of treatment, while no modulations of these biomarkers were observed during the preceding 7-14-days period, likely due to persistent inflammation. Micro-CT morphological data evaluated on day 28 were confirmed by lung histology and bronchoalveolar lavage fluid (BALF) cells; Once again, the NINT 7-21 regimen did not provide substantial benefits over the NINT 14-28. Interestingly, both NINT treatments failed to improve micro-CT-derived functional parameters. Altogether, our findings support the need for optimized protocols in preclinical studies to expedite the drug discovery process for antifibrotic agents. This study represents a significant advancement in pulmonary fibrosis animal modeling and antifibrotic treatment understanding, with the potential for improved translatability through the concurrent structural-functional analysis offered by longitudinal micro-CT.
Topics: Animals; Bleomycin; Disease Models, Animal; Mice; X-Ray Microtomography; Indoles; Antifibrotic Agents; Lung; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Mice, Inbred C57BL; Time Factors
PubMed: 38926490
DOI: 10.1038/s41598-024-65030-3 -
BMJ Open Jun 2024Norepinephrine (NE) is the first-line recommended vasopressor for restoring mean arterial pressure (MAP) in vasoplegic syndrome (vs) following cardiac surgery with...
Norepinephrine weaning guided by the Hypotension Prediction Index in vasoplegic shock after cardiac surgery: protocol for a single-centre, open-label randomised controlled trial - the NORAHPI study.
INTRODUCTION
Norepinephrine (NE) is the first-line recommended vasopressor for restoring mean arterial pressure (MAP) in vasoplegic syndrome (vs) following cardiac surgery with cardiopulmonary bypass. However, solely focusing on target MAP values can lead to acute hypotension episodes during NE weaning. The Hypotension Prediction Index (HPI) is a machine learning algorithm embedded in the Acumen IQ device, capable of detecting hypotensive episodes before their clinical manifestation. This study evaluates the clinical benefits of an NE weaning strategy guided by the HPI.
MATERIAL AND ANALYSIS
The Norahpi trial is a prospective, open-label, single-centre study that randomises 142 patients. Inclusion criteria encompass adult patients scheduled for on-pump cardiac surgery with postsurgical NE administration for vs patient randomisation occurs once they achieve haemodynamic stability (MAP>65 mm Hg) for at least 4 hours on NE. Patients will be allocated to the intervention group (n=71) or the control group (n=71). In the intervention group, the NE weaning protocol is based on MAP>65 mmHg and HPI<80 and solely on MAP>65 mm Hg in the control group. Successful NE weaning is defined as achieving NE weaning within 72 hours of inclusion. An intention-to-treat analysis will be performed. The primary endpoint will compare the duration of NE administration between the two groups. The secondary endpoints will include the prevalence, frequency and time of arterial hypotensive events monitored by the Acumen IQ device. Additionally, we will assess cumulative diuresis, the total dose of NE, and the number of protocol weaning failures. We also aim to evaluate the occurrence of postoperative complications, the length of stay and all-cause mortality at 30 days.
ETHICS AND DISSEMINATION
Ethical approval has been secured from the Institutional Review Board (IRB) at the University Hospital of Amiens (IRB-ID:2023-A01058-37). The findings will be shared through peer-reviewed publications and presentations at national and international conferences.
TRIAL REGISTRATION NUMBER
NCT05922982.
Topics: Humans; Vasoplegia; Hypotension; Prospective Studies; Norepinephrine; Cardiac Surgical Procedures; Vasoconstrictor Agents; Randomized Controlled Trials as Topic; Postoperative Complications; Machine Learning
PubMed: 38926148
DOI: 10.1136/bmjopen-2024-084499 -
Heart (British Cardiac Society) Jun 2024Despite restoration of epicardial blood flow in acute ST-elevation myocardial infarction (STEMI), inadequate microcirculatory perfusion is common and portends a poor...
BACKGROUND
Despite restoration of epicardial blood flow in acute ST-elevation myocardial infarction (STEMI), inadequate microcirculatory perfusion is common and portends a poor prognosis. Intracoronary (IC) thrombolytic therapy can reduce microvascular thrombotic burden; however, contemporary studies have produced conflicting outcomes.
OBJECTIVES
This meta-analysis aims to evaluate the efficacy and safety of adjunctive IC thrombolytic therapy at the time of primary percutaneous coronary intervention (PCI) among patients with STEMI.
METHODS
Comprehensive literature search of six electronic databases identified relevant randomised controlled trials. The primary outcome was major adverse cardiac events (MACE). The pooled risk ratio (RR) and weighted mean difference (WMD) with a 95% CI were calculated.
RESULTS
12 studies with 1915 patients were included. IC thrombolysis was associated with a significantly lower incidence of MACE (RR=0.65, 95% CI 0.51 to 0.82, I=0%, p<0.0004) and improved left ventricular ejection fraction (WMD=1.87; 95% CI 1.07 to 2.67; I=25%; p<0.0001). Subgroup analysis demonstrated a significant reduction in MACE for trials using non-fibrin (RR=0.39, 95% CI 0.20 to 0.78, I=0%, p=0.007) and moderately fibrin-specific thrombolytic agents (RR=0.62, 95% CI 0.47 to 0.83, I=0%, p=0.001). No significant reduction was observed in studies using highly fibrin-specific thrombolytic agents (RR=1.10, 95% CI 0.62 to 1.96, I=0%, p=0.75). Furthermore, there were no significant differences in mortality (RR=0.91; 95% CI 0.48 to 1.71; I=0%; p=0.77) or bleeding events (major bleeding, RR=1.24; 95% CI 0.47 to 3.28; I=0%; p=0.67; minor bleeding, RR=1.47; 95% CI 0.90 to 2.40; I=0%; p=0.12).
CONCLUSION
Adjunctive IC thrombolysis at the time of primary PCI in patients with STEMI improves clinical and myocardial perfusion parameters without an increased rate of bleeding. Further research is needed to optimise the selection of thrombolytic agents and treatment protocols.
PubMed: 38925881
DOI: 10.1136/heartjnl-2024-324078 -
European Respiratory Review : An... Apr 2024Lower respiratory tract infections (LRTIs) present a significant global health burden, exacerbated by the rise in antimicrobial resistance (AMR). The persistence and... (Review)
Review
Lower respiratory tract infections (LRTIs) present a significant global health burden, exacerbated by the rise in antimicrobial resistance (AMR). The persistence and evolution of multidrug-resistant bacteria intensifies the urgency for alternative treatments. This review explores bacteriophage (phage) therapy as an innovative solution to combat bacterial LRTIs. Phages, abundant in nature, demonstrate specificity towards bacteria, minimal eukaryotic toxicity, and the ability to penetrate and disrupt bacterial biofilms, offering a targeted approach to infection control. The article synthesises evidence from systematic literature reviews spanning 2000-2023, and studies, case reports and ongoing clinical trials. It highlights the synergistic potential of phage therapy with antibiotics, the immunophage synergy in animal models, and the pharmacodynamics and pharmacokinetics critical for clinical application. Despite promising results, the article acknowledges that phage therapy is at a nascent stage in clinical settings, the challenges of phage-resistant bacteria, and the lack of comprehensive cost-effectiveness studies. It stresses the need for further research to optimise phage therapy protocols and navigate the complexities of phage-host interactions, particularly in vulnerable populations such as the elderly and immunocompromised. We call for regulatory adjustments to facilitate the exploration of the long-term effects of phage therapy, aiming to incorporate this old-yet-new therapy into mainstream clinical practice to tackle the looming AMR crisis.
Topics: Humans; Phage Therapy; Respiratory Tract Infections; Animals; Anti-Bacterial Agents; Bacteriophages; Treatment Outcome; Bacterial Infections; Bacteria; Host-Pathogen Interactions
PubMed: 38925791
DOI: 10.1183/16000617.0029-2024 -
BMJ Open Jun 2024Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage heart failure. Compared with the best medical therapy,...
BACKGROUND
Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage heart failure. Compared with the best medical therapy, LVADs improve survival and enhance functional capacity and quality of life. However, two major complications compromise this patient population's outcomes: thrombosis and bleeding. Despite technological innovations and better hemocompatibility, these devices alter the rheology, triggering the coagulation cascade and, therefore, require antithrombotic therapy. Anticoagulation and antiplatelet therapies represent the current standard of care. Still, inconsistency in the literature exists, especially whether antiplatelet therapy is required, whether direct oral anticoagulants can replace vitamin K antagonists and even whether phosphodiesterase type 5 inhibitors with their antithrombotic effects could be added to the regimen of anticoagulation.
METHODS AND ANALYSIS
We will perform a living systematic review with network meta-analysis and indirect comparison between current antithrombotic therapies, which have and have not been directly compared within clinical trials and observational studies. We will systematically search the following electronic sources: Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE). We will exclusively examine studies published in English from 2016 to the present. Studies conducted before 2016 will be omitted since our primary focus is evaluating continuous flow devices. Two independent reviewers will assess the articles by title, abstract and full text; any disagreement will be resolved through discussion, and a third reviewer will be involved if necessary. The Cochrane Risk of Bias tool will be used to assess the risk of bias. We will then conduct a pairwise meta-analysis; if the assumption of transitivity is satisfied, we will proceed with network meta-analysis using Bayesian methodology.
ETHICS AND DISSEMINATION
Formal ethical approval is not required as no primary data are collected. This systematic review and network meta-analysis will delineate the risks of stroke, thromboembolic events, pump thrombosis, gastrointestinal bleeding and mortality in patients equipped with LVADs who are subjected to various antithrombotic regimens. The findings will be disseminated via a peer-reviewed publication and presented at conference meetings. This will enhance clinical practice and guide future research on anticoagulation strategies within this distinct patient cohort.
PROSPERO REGISTRATION NUMBER
CRD42023465288.
Topics: Humans; Heart-Assist Devices; Systematic Reviews as Topic; Network Meta-Analysis; Fibrinolytic Agents; Anticoagulants; Thrombosis; Heart Failure; Platelet Aggregation Inhibitors; Research Design; Hemorrhage
PubMed: 38925683
DOI: 10.1136/bmjopen-2023-080110 -
Cancer Reports (Hoboken, N.J.) Jun 2024Reduced ovarian reserve is among the crucial long-term side effects of using chemotherapy agents in breast cancer, yielding early ovarian failure. On the other hand,... (Randomized Controlled Trial)
Randomized Controlled Trial
The protective effect of vitamin D on ovarian reserve and anti-mullerian hormone in patients undergoing chemotherapy for breast cancer, a randomized phase ΙΙ clinical trial.
BACKGROUND
Reduced ovarian reserve is among the crucial long-term side effects of using chemotherapy agents in breast cancer, yielding early ovarian failure. On the other hand, vitamin D is an essential factor in protecting the follicles and an important predictive factor for successful IVF therapy.
AIM
The aim of this study is evaluation of vitamin D as a agent that can reduce fertility complications of chemotherapy specially in young women.
METHODS
Breast cancer patients undergoing chemotherapy at two cancer institutes were enrolled in this study. The case group received 1000 IU of calcitriol, and the AMH level was measured at the baseline, after chemotherapy, and six months after chemotherapy. The primary end point was improvement in the AMH level after six months of chemotherapy. the secondary endpoint was to evaluate the predictive factors of AMH level decline during chemotherapy.
RESULTS
Between 2018 and 2019, 18 and 15 patients were enrolled in the case and control groups, respectively. The mean AMH level (ngr/ml) of the patients in the case and control group were 3.16 and 2.37 ng/mL, respectively (p-value = .16). These levels were 0.387 and 0.19 after six months (p-value = .38). The AMH rise immediately after chemotherapy cycles to six months after chemotherapy, in the case and control groups were 0.86 and 0.44 ng/mL, respectively, which was slightly higher in the case group but not statistically significant between two groups (p-value = .054).
CONCLUSION
Despite a minimal rise in the AMH level after six months of chemotherapy, the study could not demonstrate any protective effect of vitamin D on patients' ovarian reserve undergoing chemotherapy for breast cancer. Further larger studies are needed to evaluate the effect of vitamin D supplements on ovarian reserve beside optimal dose and duration.
Topics: Humans; Female; Anti-Mullerian Hormone; Ovarian Reserve; Breast Neoplasms; Adult; Vitamin D; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38925607
DOI: 10.1002/cnr2.2104 -
Cancer Medicine Jun 2024Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore,...
AIM
Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs.
METHODS
This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed.
RESULTS
The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105-0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157-10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin-bilirubin score (HR: 9.083, 95% CI: 1.118-73.76) was associated with bleeding events (p = 0.039).
CONCLUSIONS
DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.
Topics: Humans; Carcinoma, Hepatocellular; Male; Liver Neoplasms; Female; Antibodies, Monoclonal, Humanized; Retrospective Studies; Lung Neoplasms; Aged; Middle Aged; Feasibility Studies; Hemorrhage; Bevacizumab; Antineoplastic Combined Chemotherapy Protocols; Anticoagulants; Administration, Oral; Aged, 80 and over
PubMed: 38924675
DOI: 10.1002/cam4.7430 -
PloS One 2024Maternal disorders are the third leading cause of sepsis globally, accounting for 5.7 million (12%) cases in 2017. There are increasing concerns about the emergence of...
INTRODUCTION
Maternal disorders are the third leading cause of sepsis globally, accounting for 5.7 million (12%) cases in 2017. There are increasing concerns about the emergence of antimicrobial resistance (AMR) in bacteria commonly causing maternal sepsis. Our aim is to describe the protocol for a clinical and microbiology laboratory study to understand risk factors for and the bacterial etiology of maternal sepsis in a tertiary Obstetrics and Gynaecology Hospital.
METHODS
This case-control study aims to recruit 100 cases and 200 controls at Tu Du Hospital in Ho Chi Minh City, Vietnam, which had approximately 55,000 births in 2022. Women aged ≥ 18 years and ≥ 28 weeks gestation having a singleton birth will be eligible for inclusion as cases or controls, unless they have an uncomplicated localised or chronic infection, or an infection with SARS-CoV-2. Cases will include pregnant or recently pregnant women with sepsis recognised between the onset of labour and/or time of delivery/cessation of pregnancy for up to 42 days post-partum. Sepsis will be defined as suspected or confirmed infection with an obstetrically modified Sequential Organ Failure Assessment score of ≥ 2, treatment with intravenous antimicrobials and requested cultures of any bodily fluid. Controls will be matched by age, location, parity, mode of delivery and gestational age. Primary and secondary outcomes are risk factors associated with the development of maternal sepsis, the frequency of adverse outcomes due to maternal sepsis, bacterial etiology and AMR profiles of cases and controls.
DISCUSSION
This study will improve understanding of the epidemiology and clinical implications of maternal sepsis management including the presence of AMR in women giving birth in Vietnam. It will help us to determine whether women in this setting are receiving optimal care and to identify opportunities for improvement.
Topics: Humans; Female; Pregnancy; Case-Control Studies; Risk Factors; Sepsis; Vietnam; Pregnancy Complications, Infectious; Adult; Anti-Bacterial Agents
PubMed: 38924013
DOI: 10.1371/journal.pone.0305411 -
JMIR MHealth and UHealth Jun 2024Globally, students face increasing mental health challenges, including elevated stress levels and declining well-being, leading to academic performance issues and mental... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Globally, students face increasing mental health challenges, including elevated stress levels and declining well-being, leading to academic performance issues and mental health disorders. However, due to stigma and symptom underestimation, students rarely seek effective stress management solutions. Conversational agents in the health sector have shown promise in reducing stress, depression, and anxiety. Nevertheless, research on their effectiveness for students with stress remains limited.
OBJECTIVE
This study aims to develop a conversational agent-delivered stress management coaching intervention for students called MISHA and to evaluate its effectiveness, engagement, and acceptance.
METHODS
In an unblinded randomized controlled trial, Swiss students experiencing stress were recruited on the web. Using a 1:1 randomization ratio, participants (N=140) were allocated to either the intervention or waitlist control group. Treatment effectiveness on changes in the primary outcome, that is, perceived stress, and secondary outcomes, including depression, anxiety, psychosomatic symptoms, and active coping, were self-assessed and evaluated using ANOVA for repeated measure and general estimating equations.
RESULTS
The per-protocol analysis revealed evidence for improvement of stress, depression, and somatic symptoms with medium effect sizes (Cohen d=-0.36 to Cohen d=-0.60), while anxiety and active coping did not change (Cohen d=-0.29 and Cohen d=0.13). In the intention-to-treat analysis, similar results were found, indicating reduced stress (β estimate=-0.13, 95% CI -0.20 to -0.05; P<.001), depressive symptoms (β estimate=-0.23, 95% CI -0.38 to -0.08; P=.003), and psychosomatic symptoms (β estimate=-0.16, 95% CI -0.27 to -0.06; P=.003), while anxiety and active coping did not change. Overall, 60% (42/70) of the participants in the intervention group completed the coaching by completing the postintervention survey. They particularly appreciated the quality, quantity, credibility, and visual representation of information. While individual customization was rated the lowest, the target group fitting was perceived as high.
CONCLUSIONS
Findings indicate that MISHA is feasible, acceptable, and effective in reducing perceived stress among students in Switzerland. Future research is needed with different populations, for example, in students with high stress levels or compared to active controls.
TRIAL REGISTRATION
German Clinical Trials Register DRKS 00030004; https://drks.de/search/en/trial/DRKS00030004.
Topics: Humans; Male; Female; Stress, Psychological; Pilot Projects; Students; Mentoring; Switzerland; Adult; Mobile Applications; Adolescent; Surveys and Questionnaires; Young Adult
PubMed: 38922677
DOI: 10.2196/54945