The latest medical research on Healthcare
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about healthcare gathered by our medical AI research bot.
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Demethylation and Up-Regulation of an Oncogene after Hypomethylating Therapy.N Engl J
Although hypomethylating agents are currently used to treat patients with cancer, whether they can also reactivate and up-regulate oncogenes is not well elucidated.
We examined the effect of hypomethylating agents on SALL4, a known oncogene that plays an important role in myelodysplastic syndrome and other cancers. Paired bone marrow samples that were obtained from two cohorts of patients with myelodysplastic syndrome before and after treatment with a hypomethylating agent were used to explore the relationships among changes in SALL4 expression, treatment response, and clinical outcome. Leukemic cell lines with low or undetectable SALL4 expression were used to study the relationship between SALL4 methylation and expression. A locus-specific demethylation technology, CRISPR-DNMT1-interacting RNA (CRISPR-DiR), was used to identify the CpG island that is critical for SALL4 expression.
SALL4 up-regulation after treatment with hypomethylating agents was observed in 10 of 25 patients (40%) in cohort 1 and in 13 of 43 patients (30%) in cohort 2 and was associated with a worse outcome. Using CRISPR-DiR, we discovered that demethylation of a CpG island within the 5' untranslated region was critical for SALL4 expression. In cell lines and patients, we confirmed that treatment with a hypomethylating agent led to demethylation of the same CpG region and up-regulation of SALL4 expression.
By combining analysis of patient samples with CRISPR-DiR technology, we found that demethylation and up-regulation of an oncogene after treatment with a hypomethylating agent can indeed occur and should be further studied. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.).
Protection and Waning of Natural and Hybrid Immunity to SARS-CoV-2.N Engl J
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown.
Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event.
The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously.
Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.
A multisystem, cardio-renal investigation of post-COVID-19 illness.Nature Medicine
The pathophysiology and trajectory of post-Coronavirus Disease 2019 (COVID-19) syndrome is uncertain. To clarify multisystem involvement, we undert...
Effectiveness of CoronaVac in children 3 to 5 years during the SARS-CoV-2 Omicron outbreak in Chile.Nature Medicine
The outbreak of the B.1.1.529 lineage of SARS-CoV-2 (Omicron) has caused an unprecedented number of COVID-19 cases, including pediatric hospital ad...
The Aveir Leadless Pacing System receives FDA approval.Journal of Artificial Intelligence Research
The Aveir leadless system is now the second device on the market in the United States to offer safe and reliable pacemaking capabilities to patient...
Acquired platelet defects are responsible for non-surgical bleeding in left ventricular assist device recipients.Journal of Artificial Intelligence Research
Left ventricular assist devices (LVADs) have been used as a standard treatment option for patients with advanced heart failure. However, these devices are prone to adverse events. Non-surgical bleeding (NSB) is the most common complication in patients with continuous flow (CF) LVADs. The development of acquired von Willebrand syndrome (AVWS) in CF-LVAD recipients is thought to be a key factor. However, AVWS is seen across a majority of LVAD patients, not just those with NSB. The purpose of this study was to examine the link between acquired platelet defects and NSB in CF-LVAD patients.
Blood samples were collected from 62 CF-LVAD patients at pre- and post-implantation timepoints. Reduced adhesion receptor expression (GPIbα and GPVI) and activation of platelets (GPIIb/IIIa activation) were used as markers for acquired platelet defects.
Twenty-three patients experienced at least one NSB episode. Significantly higher levels of platelet activation and receptor reduction were seen in the post-implantation blood samples from bleeders compared with non-bleeders. All patients experienced the loss of high molecular weight monomers (HMWM) of von Willebrand Factor (vWF), but no difference was seen between the two groups. Multivariable logistic regression showed that biomarkers for reduced platelet receptor expression (GPIbα and GPVI) and activation (GPIIb/IIIa) have more predictive power for NSB, with the area under curve (AUC) values of 0.72, 0.68, and 0.62, respectively, than the loss of HMWM of vWF (AUC: 0.57).
The data from this study indicated that the severity of acquired platelet defects has a direct link to NSB in CF-LVAD recipients.
Cost-effectiveness of the Victorian Stroke Telemedicine program.Aust Health Rev
ObjectiveStroke telemedicine improves the provision of reperfusion therapies in regional hospitals, yet evidence of its cost-effectiveness using pa...
Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial.Nature Medicine
Patients with rheumatoid arthritis (RA) receive highly targeted biologic therapies without previous knowledge of target expression levels in the di...
Hospitalisation costs of primary liver cancer in Australia: evidence from a data-linkage study.Aust Health Rev
ObjectiveThis study aimed to estimate the public hospital costs associated with primary liver cancer (PLC) in the first and second years following ...
Unexplained post-acute infection syndromes.Nature Medicine
SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chroni...
Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.Nature Medicine
A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silic...
Results of Two Cases of Pig-to-Human Kidney Xenotransplantation.N Engl J
Xenografts from genetically modified pigs have become one of the most promising solutions to the dearth of human organs available for transplantation. The challenge in this model has been hyperacute rejection. To avoid this, pigs have been bred with a knockout of the alpha-1,3-galactosyltransferase gene and with subcapsular autologous thymic tissue.
We transplanted kidneys from these genetically modified pigs into two brain-dead human recipients whose circulatory and respiratory activity was maintained on ventilators for the duration of the study. We performed serial biopsies and monitored the urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection.
The xenograft in both recipients began to make urine within moments after reperfusion. Over the 54-hour study, the kinetic eGFR increased from 23 ml per minute per 1.73 m2 of body-surface area before transplantation to 62 ml per minute per 1.73 m2 after transplantation in Recipient 1 and from 55 to 109 ml per minute per 1.73 m2 in Recipient 2. In both recipients, the creatinine level, which had been at a steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in Recipient 1 and from 1.10 to 0.57 mg per deciliter in Recipient 2. The transplanted kidneys remained pink and well-perfused, continuing to make urine throughout the study. Biopsies that were performed at 6, 24, 48, and 54 hours revealed no signs of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with the native kidneys.
Genetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. (Funded by Lung Biotechnology.).