Associated Factors of Cardiopulmonary Resuscitation Outcomes; a Cohort Study on an Adult In-hospital Cardiac Arrest Registry.

Introduction: In-hospital cardiac arrest (IHCA) remains a substantial cause of morbidity and mortality for hospitalized patients worldwide. This study aimed to identify associated factors of return of spontaneous circulation (ROSC) and survival with favorable neurological outcomes of IHCA patients. Method: A two-year retrospective cohort study was conducted at a university-based tertiary care hospital in Bangkok, Thailand, studying adult patients aged ≥ 18 years with IHCA from January 2021 to December 2022. The primary endpoint was sustained ROSC, and the secondary endpoint was survival with favorable neurological outcomes defined as Cerebral Performance Categories (CPC) Scale of 1 or 2 at discharge. Pre-arrest and intra-arrest variables were collected and analyzed using multivariable logistic regression to identify independent factors associated with the outcomes. Results: During the study period, 156 patients were included in the study. 105 (67.3%) patients achieved sustained ROSC after the CPR, 28 patients (18.0%) were discharged alive, and 15 patients (9.6%) survived with a favorable neurological outcome at hospital discharge. Overall, sustained ROSC was higher in patients who had IHCA during the day shift (odds ratio (OR): 4.11; 95% confidence interval (CI): 1.05-16.06) and electrocardiogram (ECG) monitoring prior to arrest (OR: 6.38; 95% CI: 1.18-34.54). In contrast, higher adrenaline doses administrated, and increased CPR duration reduced the odds of sustained ROSC (OR: 0.72; 95% CI: 0.54-0.94 and OR: 0.92; 95% CI: 0.85-0.98, respectively). Arrest due to cardiac etiology was associated with increased discharged survival with favorable neurological outcomes (OR: 13.43; 95% CI: 2.00-89.80), while a higher Good Outcome Following Attempted Resuscitation (GO-FAR) score reduced the odds of the secondary outcome (OR: 0.89; 95% CI: 0.81-0.98). Conclusion: The sustained ROSC was higher in IHCA during the daytime shift and under prior ECG monitoring. The administration of higher doses of adrenaline and prolonged CPR durations decreased the likelihood of achieving sustained ROSC. Furthermore, patients with cardiac-related causes of cardiac arrest exhibited a higher rate of survival to hospital discharge with favorable neurological outcomes.

Comparison of the efficacy of second and third generation lentiviral vector transduced CAR CD19 T cells for use in the treatment of acute lymphoblastic leukemia both in vitro and in vivo models.

T cells genetically engineered to express a chimeric antigen receptor (CAR) specifically binding to a CD19 antigen has become the frontline of hematological malignancies immunotherapy. Their remarkable antitumor effect has exerted complete remission in treating B-cell malignancies. Although successful patient treatment has been shown, improvement to the structure of CAR to enhance its safety and efficacy profile is warranted. Transduction with a lentiviral vector (LVV) leading to the expression of CARs is also a critical step in redirecting T cells to target specific tumor antigens. To improve the efficacy of CD19 CARs in this study, the transduction ability of second and third generations LVV were compared. Ex vivo expansion of CD19 CARs T cells from healthy donors' peripheral blood mononuclear cells was performed after transduction of T cells with second and third generations LVV. Transduction efficacy of transduced T cells was determined to show a higher percentage in the third generations LVV transduced cells, with no changes in viability and identity of cells characterized by immunophenotyping. Testing the cytotoxic capacity of third generations LVV-transduced T cells against target cells showed higher reactivity against control cells. Cytokine expression was detected on the CD19 CARs T cells, suggesting that these cells limit in vitro growth of B-cell leukemia via secretion of the pro-inflammatory cytokine IFN γ. To investigate whether the third generation LVV transduced T cells can limit CD19 lymphoma growth in vivo, an analysis of tumor burden in a mouse model assessed by bioluminescence imaging was performed. We found that, in the presence of CD19 CARs T cells, the level of tumor burden was markedly reduced. In addition, an increase in the length of survival in mice receiving CAR-CD19 T cells was also observed. This suggests that transduction with third generations LVV generate a functional CAR-CD19 T cells, which may provide a safer and effective therapy for B-cell malignancies.

The Future of Gene Therapy for Transfusion-Dependent Beta-Thalassemia: The Power of the Lentiviral Vector for Genetically Modified Hematopoietic Stem Cells.

ß-thalassemia, a disease that results from defects in ß-globin synthesis, leads to an imbalance of ß- and α-globin chains and an excess of α chains. Defective erythroid maturation, ineffective erythropoiesis, and shortened red blood cell survival are commonly observed in most ß-thalassemia patients. In severe cases, blood transfusion is considered as a mainstay therapy; however, regular blood transfusions result in chronic iron overload with life-threatening complications, e.g., endocrine dysfunction, cardiomyopathy, liver disease, and ultimately premature death. Therefore, transplantation of healthy hematopoietic stem cells (HSCs) is considered an alternative treatment. Patients with a compatible human leukocyte antigen (HLA) matched donor can be cured by allogeneic HSC transplantation. However, some recipients faced a high risk of morbidity/mortality due to graft versus host disease or graft failure, while a majority of patients do not have such HLA match-related donors. Currently, the infusion of autologous HSCs modified with a lentiviral vector expressing the ß-globin gene into the erythroid progenitors of the patient is a promising approach to completely cure ß-thalassemia. Here, we discuss a history of ß-thalassemia treatments and limitations, in particular the development of ß-globin lentiviral vectors, with emphasis on clinical applications and future perspectives in a new era of medicine.

Light-intensity Activity-related Nausea: An Unusual Presentation of Pheochromocytoma.

Pheochromocytomas are rare neuroendocrine tumors arising from chromaffin cells of the adrenal gland. Because of their highly variable clinical spectrum, these tumors often go undiagnosed and result in life-threatening complications. The typical presentations include episodic headache, palpitations and sweating accompanied with sustained or paroxysmal hypertension. However, less than half of pheochromocytoma patients have these classic symptoms. Many patients present with atypical symptoms, which could be overlooked. Our case represents an unusual presentation of pheochromocytoma, which is not well recognized as a possible manifestation. A 60-year-old woman presented with light-intensity-related nausea, which progressed to severe vomiting with hypovolemic shock. An unexpected adrenal mass was found during sonographic evaluation of the volume status. Pheochromocytoma was confirmed by 24-hour urine fractionated metanephrines and a computed tomography (CT) scan. In pheochromocytomas, the elevation of circulating catecholamines activates alpha-adrenergic receptors in the area postrema, which then initiates the emetic cascade. Light-intensity activity-related nausea and vomiting, especially when present with other symptoms of catecholamine excess, could be considered as a clinical presentation of pheochromocytomas.