Clinical outcomes associated with type II myocardial infarction caused by bleeding.

BACKGROUND: Type ll myocardial infarction (T2MI) is caused by a mismatch between myocardial oxygen supply and demand. One subset of individuals is T2MI caused by acute hemorrhage. Traditional MI treatments including antiplatelets, anticoagulants, and revascularization can worsen bleeding. We aim to report outcomes of T2MI patients due to bleeding, stratified by treatment approach. METHODS: The MGB Research Patient Data Registry followed by manual physician adjudication was used to identify individuals with T2MI caused by bleeding between 2009 and 2022. We defined 3 treatment groups: (1) invasively managed, (2) pharmacologic, and (3) conservatively managed Clinical parameters and outcomes for 30-day, mortality, rebleeding, and readmission were abstracted compared between the treatment groups. RESULTS: We identified 5,712 individuals coded with acute bleeding, of which 1,017 were coded with T2MI during their admission. After manual physician adjudication, 73 individuals met the criteria for T2MI caused by bleeding. 18 patients were managed invasively, 39 received pharmacologic therapy alone, and 16 were managed conservatively. The invasively managed group experienced lower mortality (P = .021) yet higher readmission (P = .045) than the conservatively managed group. The pharmacologic group also experienced lower mortality (P= .017) yet higher readmission (P = .005) than the conservatively managed group. CONCLUSION: Individuals with T2MI associated with acute hemorrhage are a high-risk population. Patients treated with standard procedures experienced higher readmission but lower mortality than conservatively managed patients. These results raise the possibility of testing ischemia-reduction approaches for such high-risk populations. Future clinical trials are required to validate treatment strategies for T2MI caused by bleeding.

Multiparametric Profiling of Neutrophil Function via a High-Throughput Flow Cytometry-Based Assay.

Neutrophils are a vital component of the innate immune system and play an essential function in the recognition and clearance of bacterial and fungal pathogens. There is great interest in understanding mechanisms of neutrophil dysfunction in the setting of disease and deciphering potential side effects of immunomodulatory drugs on neutrophil function. We developed a high throughput flow cytometry-based assay for detecting changes to four canonical neutrophil functions following biological or chemical triggers. Our assay detects neutrophil phagocytosis, reactive oxygen species (ROS) generation, ectodomain shedding, and secondary granule release in a single reaction mixture. By selecting fluorescent markers with minimal spectral overlap, we merge four detection assays into one microtiter plate-based assay. We demonstrate the response to the fungal pathogen, Candida albicans and validate the assay's dynamic range using the inflammatory cytokines G-CSF, GM-CSF, TNFα, and IFNγ. All four cytokines increased ectodomain shedding and phagocytosis to a similar degree while GM-CSF and TNFα were more active in degranulation when compared to IFNγ and G-CSF. We further demonstrated the impact of small molecule inhibitors such as kinase inhibition downstream of Dectin-1, a critical lectin receptor responsible for fungal cell wall recognition. Bruton's tyrosine kinase (Btk), Spleen tyrosine kinase (Syk), and Src kinase inhibition suppressed all four measured neutrophil functions but all functions were restored with lipopolysaccharide co-stimulation. This new assay allows for multiple comparisons of effector functions and permits identification of distinct subpopulations of neutrophils with a spectrum of activity. Our assay also offers the potential for studying the intended and off-target effects of immunomodulatory drugs on neutrophil responses.

Novel Host Response-Based Diagnostics to Differentiate the Etiology of Fever in Patients Presenting to the Emergency Department.

Fever is a common presentation to urgent-care services and is linked to multiple disease processes. To rapidly determine the etiology of fever, improved diagnostic modalities are necessary. This prospective study of 100 hospitalized febrile patients included both positive (FP) and negative (FN) subjects in terms of infection status and 22 healthy controls (HC). We evaluated the performance of a novel PCR-based assay measuring five host mRNA transcripts directly from whole blood to differentiate infectious versus non-infectious febrile syndromes as compared to traditional pathogen-based microbiology results. The FP and FN groups observed a robust network structure with a significant correlation between the five genes. There were statistically significant associations between positive infection status and four of the five genes: IRF-9 (OR = 1.750, 95% CI = 1.16-2.638), ITGAM (OR = 1.533, 95% CI = 1.047-2.244), PSTPIP2 (OR = 2.191, 95% CI = 1.293-3.711), and RUNX1 (OR = 1.974, 95% CI = 1.069-3.646). We developed a classifier model to classify study participants based on these five genes and other variables of interest to assess the discriminatory power of the genes. The classifier model correctly classified more than 80% of the participants into their respective groups, i.e., FP or FN. The GeneXpert prototype holds promise for guiding rapid clinical decision-making, reducing healthcare costs, and improving outcomes in undifferentiated febrile patients presenting for urgent evaluation.

Dispensing and Purchasing Antibiotics Without Prescription: A Cross-sectional Study Among Pharmacists and Patients in Beirut, Lebanon.

Antimicrobial resistance is a global public health issue, exacerbated by dispensing and purchasing antibiotics without a prescription, common in low- and middle-income countries, such as Lebanon. This study aimed to (1) describe behavioral patterns underpinning dispensing and purchasing antibiotics without a prescription among pharmacists and patients, (2) describe reasons for, and (3) attitudes toward these behaviors. A cross-sectional study targeted pharmacists and patients, respectively, identified through stratified random sampling and convenience sampling from all 12 Beirut quarters. Questionnaires assessed behavioral patterns, reasons for, and attitudes toward dispensing and purchasing antibiotics without prescription among the 2 samples. A total of 70 pharmacists and 178 patients were recruited. About a third (37%) of pharmacists supported dispensing antibiotics without a prescription, considering it acceptable; 43% of patients report getting antibiotics without a prescription. Reasons for distributing and purchasing antibiotics without prescription include financial costs associated with the drugs and convenience, coupled with inexistent law enforcement. Dispensing antibiotics without prescription was shared among a relatively high proportion of pharmacists and patients residing in Beirut. Dispensing antibiotics without prescription is common in Lebanon, where law enforcement needs to be stronger. National efforts, including anti-AMR campaigns and law enforcement, must be rapidly implemented to avoid the double disease burden, especially when old and new vaccines are available, and superbugs are making preventative public health efforts more difficult.

Implications of Using Host Response-Based Molecular Diagnostics on the Management of Bacterial and Viral Infections: A Review.

Host-based diagnostics are a rapidly evolving field that may serve as an alternative to traditional pathogen-based diagnostics for infectious diseases. Understanding the exact mechanisms underlying a host-immune response and deriving specific host-response signatures, biomarkers and gene transcripts will potentially achieve improved diagnostics that will ultimately translate to better patient outcomes. Several studies have focused on novel techniques and assays focused on immunodiagnostics. In this review, we will highlight recent publications on the current use of host-based diagnostics alone or in combination with traditional microbiological assays and their potential future implications on the diagnosis and prognostic accuracy for the patient with infectious complications. Finally, we will address the cost-effectiveness implications from a healthcare and public health perspective.

Rapid Quantum Magnetic IL-6 Point-of-Care Assay in Patients Hospitalized with COVID-19.

Interleukin-6 (IL-6) has been linked to several life-threatening disease processes. Developing a point-of-care testing platform for the immediate and accurate detection of IL-6 concentrations could present a valuable tool for improving clinical management in patients with IL-6-mediated diseases. Drawing on an available biobank of samples from 35 patients hospitalized with COVID-19, a novel quantum-magnetic sensing platform is used to determine plasma IL-6 concentrations. A strong correlation was observed between IL-6 levels measured by QDTI10x and the Luminex assay (r = 0.70, p-value < 0.001) and between QDTI80x and Luminex (r = 0.82, p-value < 0.001). To validate the non-inferiority of QDTI to Luminex in terms of the accuracy of IL-6 measurement, two clinical parameters­the need for intensive care unit admission and the need for mechanical intubation­were chosen. IL-6 concentrations measured by the two assays were compared with respect to these clinical outcomes. Results demonstrated a comparative predictive performance between the two assays with a significant correlation coefficient. Conclusion: In short, the QDTI assay holds promise for implementation as a potential tool for rapid clinical decision in patients with IL-6-mediated diseases. It could also reduce healthcare costs and enable the development of future various biomolecule point-of-care tests for different clinical scenarios.

Transfusable neutrophil progenitors as cellular therapy for the prevention of invasive fungal infections.

The use of mature neutrophil (granulocyte) transfusions for the treatment of neutropenic patients with invasive fungal infections (IFIs) has been the focus of multiple clinical trials. Despite these efforts, the transfusion of mature neutrophils has resulted in limited clinical benefit, likely owing to problems of insufficient numbers and the very short lifespan of these donor cells. In this report, we employed a system of conditionally immortalized murine neutrophil progenitors that are capable of continuous expansion, allowing for the generation of unlimited numbers of homogenous granulocyte-macrophage progenitors (GMPs). These GMPs were assayed in vivo to demonstrate their effect on survival in 2 models of IFI: candidemia and pulmonary aspergillosis. Mature neutrophils derived from GMPs executed all cardinal functions of neutrophils. Transfused GMPs homed to the bone marrow and spleen, where they completed normal differentiation to mature neutrophils. These neutrophils were capable of homing and extravasation in response to inflammatory stimuli using a sterile peritoneal challenge model. Furthermore, conditionally immortalized GMP transfusions significantly improved survival in models of candidemia and pulmonary aspergillosis. These data confirm the therapeutic benefit of prophylactic GMP transfusions in the setting of neutropenia and encourage development of progenitor cellular therapies for the management of fungal disease in high-risk patients.

The use of heparin and heparin-like molecules in cancer treatment: a review.

BACKGROUND: Heparin and heparin-like molecules have shown some promise in the treatment of several cancers. These molecules have roles in angiogenesis, cell proliferation, immune system modulation, cell migration, and cellular invasion. The pathways and mechanisms used by these molecules to inhibit the proliferation of cancer cells aid in understanding the utilization of these molecules in potential treatments. Our aim is to review the use of heparin and heparin-like molecules in cancer treatment, explore the results, and discuss their potential downfalls. METHODS: Publications on heparin and heparin-like molecules and compounds were collected from the PubMed and EMBASE databases. Boolean operators and MeSH terms related to heparin, heparin-like molecules, and cancer were used to conduct this search. The articles were reviewed by the authors. RESULTS: Several heparin mimetics are showing promise in cancer treatment. Various studies using mimetics alone or in combination with chemotherapy have been conducted and have yielded mixed results. They work on multiple target molecules, mostly receptors such as fibroblast growth factor and endothelial growth factor. The main types of cancers targeted by these drugs are multiple myeloma, pancreatic cancer, hepatocellular carcinoma (HCC), and other solid tumors. CONCLUSION: Although limited clinical evidence of efficacy and potential pitfalls are present, heparin and heparin-like molecules have shown potential in the management of cancer patients. Additional research is required to fully understand the biological mechanisms utilized by these molecules in cancer treatment.