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Swiss Medical Weekly May 2024Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was...
AIM
Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was the main indication for allogeneic HCT. The introduction of tyrosine kinase inhibitors changed the treatment of CML patients dramatically. Allogeneic HCT was rapidly replaced by tyrosine kinase inhibitors as first-line treatment for CML, and the indication shifted to the treatment of non-responders, patients intolerant to tyrosine kinase inhibitors and patients whose CML is transforming to the accelerated phase and blast crisis. This paper describes changes in the use of transplantation technology for CML patients in the face of rapid drug development.
METHODS
All patients receiving a transplant for CML between 1997 and 2021 in Switzerland were included in the study. For the purpose of this analysis, time periods were analysed in quinquennia, 1997-2001 (Q1), 2002-2006 (Q2), 2007-2011 (Q3), 2012-2016 (Q4) and 2017-2021 (Q5), as the observation period spanned 25 years.
RESULTS
Overall, 239 patients received a transplant. These included 96 in Q1, 56 in Q2, 25 in Q3, 34 in Q4 and 28 in Q5. Patient characteristics changed over time: recent patients were older and had a longer interval from diagnosis to transplantation because of tyrosine kinase inhibitor treatment. However, the proportions of patients receiving transplants during an early versus advanced disease stage differed little. Transplant technology changed, as well. Patients received intensive conditioning regimens less often due to higher age and more commonly had peripheral blood as opposed to bone marrow transplants. However, the type of stem cell donor selected did not differ. In a univariable analysis, there were no significant differences in survival, progression-free survival, non-relapse mortality, relapse incidence or incidences of acute and chronic graft-versus-host disease among the five quinquennia. In a multivariable analysis, older age, donors other than HLA-identical siblings and more advanced disease stage, but not the quinquennium, were associated with higher risk of death.
CONCLUSION
Since the introduction of tyrosine kinase inhibitors haematopoietic cell transplantation has been used less frequently to treat CML. Patients in recent cohorts received transplants at an older age and later in the disease course; despite these higher risks, the outcome of allogeneic HCT has not worsened over time but has not improved, either. As the outcome is worse in advanced phases, it is important to conduct transplants before disease progression. Therefore, patients with advanced disease should be monitored closely and receive transplants in time.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Switzerland; Male; Female; Adult; Middle Aged; Transplantation, Homologous; Protein Kinase Inhibitors; Adolescent; Transplantation Conditioning
PubMed: 38749067
DOI: 10.57187/s.3754 -
Swiss Medical Weekly May 2024With the emergence of newer SARS-CoV-2 variants and their substantial effects on the levels and duration of protection against infection, an understanding of these... (Review)
Review
INTRODUCTION
With the emergence of newer SARS-CoV-2 variants and their substantial effects on the levels and duration of protection against infection, an understanding of these characteristics of the protection conferred by humoral and cellular immunity can aid in the proper development and implementation of vaccine and safety guidelines.
METHODS
We conducted a rapid literature review and searched five electronic databases weekly from 1 November 2021 to 30 September 2022. Studies that assessed the humoral or cellular immunity conferred by infection, vaccination or a hybrid (combination of both) in adults and risk groups (immunocompromised and older populations) were identified. Studies were eligible when they reported data on immunological assays of COVID-19 (related to vaccination and/or infection) or the effectiveness of protection (related to the effectiveness of vaccination and/or infection).
RESULTS
We screened 5103 studies and included 205 studies, of which 70 provided data on the duration of protection against SARS-CoV-2 infection. The duration of protection of adaptive immunity was greatly impacted by Omicron and its subvariants: levels of protection were low by 3-6 months from exposure to infection/vaccination. Although more durable, cellular immunity also showed signs of waning by 6 months. First and second mRNA vaccine booster doses increased the levels of protection against infection and severe disease from Omicron and its subvariants but continued to demonstrate a high degree of waning over time.
CONCLUSION
All humoral immunities (infection-acquired, vaccine-acquired and hybrid) waned by 3-6 months. Cellular immunity was more durable but showed signs of waning by 6 months. Hybrid immunity had the highest magnitude of protection against SARS-CoV-2 infection. Boosting may be recommended as early as 3-4 months after the last dose, especially in risk groups.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Immunity, Cellular; Immunity, Humoral; Immunization, Secondary; Vaccination
PubMed: 38749028
DOI: 10.57187/s.3732 -
Jornal Brasileiro de Nefrologia 2024Acute kidney injury (AKI) is an abrupt deterioration of kidney function. The incidence of pediatric AKI is increasing worldwide, both in critically and non-critically... (Observational Study)
Observational Study
INTRODUCTION
Acute kidney injury (AKI) is an abrupt deterioration of kidney function. The incidence of pediatric AKI is increasing worldwide, both in critically and non-critically ill settings. We aimed to characterize the presentation, etiology, evolution, and outcome of AKI in pediatric patients admitted to a tertiary care center.
METHODS
We performed a retrospective observational single-center study of patients aged 29 days to 17 years and 365 days admitted to our Pediatric Nephrology Unit from January 2012 to December 2021, with the diagnosis of AKI. AKI severity was categorized according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The outcomes considered were death or sequelae (proteinuria, hypertension, or changes in renal function at 3 to 6 months follow-up assessments).
RESULTS
Forty-six patients with a median age of 13.0 (3.5-15.5) years were included. About half of the patients (n = 24, 52.2%) had an identifiable risk factor for the development of AKI. Thirteen patients (28.3%) were anuric, and all of those were categorized as AKI KDIGO stage 3 (p < 0.001). Almost one quarter (n = 10, 21.7%) of patients required renal replacement therapy. Approximately 60% of patients (n = 26) had at least one sequelae, with proteinuria being the most common (n = 15, 38.5%; median (P25-75) urinary protein-to-creatinine ratio 0.30 (0.27-0.44) mg/mg), followed by reduced glomerular filtration rate (GFR) (n = 11, 27.5%; median (P25-75) GFR 75 (62-83) mL/min/1.73 m2).
CONCLUSIONS
Pediatric AKI is associated with substantial morbidity, with potential for proteinuria development and renal function impairment and a relevant impact on long-term prognosis.
Topics: Humans; Acute Kidney Injury; Retrospective Studies; Child; Tertiary Care Centers; Adolescent; Female; Male; Child, Preschool; Nephrology; Risk Factors; Infant; Severity of Illness Index; Renal Replacement Therapy; Proteinuria
PubMed: 38748945
DOI: 10.1590/2175-8239-JBN-2024-0012en -
PloS One 2024Episiotomy is associated with side effects, such as pain and wound infection. Additionally, discomfort after episiotomy affects the quality of life of both the mother... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized controlled trial of the effectiveness of olive and black seed oil combination on pain intensity and episiotomy wound healing in primiparous women: A study protocol.
BACKGROUND
Episiotomy is associated with side effects, such as pain and wound infection. Additionally, discomfort after episiotomy affects the quality of life of both the mother and the baby. Medicinal herbs are one alternative method for the treatment of episiotomy wounds. This study will investigate the effectiveness of the combination of olive and black seed oil on pain intensity and the healing of episiotomy wounds in primiparous women.
METHODS
This randomized clinical trial will be conducted on primiparous women who have had a normal delivery with an episiotomy. There are 3 groups in this study: one group will receive a combination of olive oil and black seed oil, another group will receive olive oil alone, and the use of oils will start 24 hours after delivery. Ten drops will be applied topically 3 times a day for 10 days. The third group (control) will receive only routine care. Data will be collected through a demographic characteristics questionnaire, REEDA (Redness, Edema, Ecchymosis, Discharge, and Approximation) Scale, and Visual Analog Scale. To determine and compare the effects of pharmaceutical interventions on pain intensity and episiotomy wound healing in the groups, an analysis of variance (ANOVA) test with repeated measurements will be used with SPSS version 22.
DISCUSSION
The results of this study will show the effects of a combination of olive and black seed oil, as well as olive oil alone, on pain intensity and episiotomy wound healing in primiparous women. The positive effects observed in this trial with these oils could be valuable for women who have undergone an episiotomy.
Topics: Humans; Female; Episiotomy; Olive Oil; Wound Healing; Plant Oils; Adult; Pregnancy; Pain Measurement; Parity; Young Adult
PubMed: 38748938
DOI: 10.1371/journal.pone.0302161 -
The American Journal of Managed Care May 2024Given the problematic fragmentation of care for patients with end-stage kidney disease (ESKD), a kidney care organization and an integrated health system within a large...
OBJECTIVES
Given the problematic fragmentation of care for patients with end-stage kidney disease (ESKD), a kidney care organization and an integrated health system within a large accountable care organization partnered to best utilize their individual capabilities to collaborate around their shared patients in a coordinated care approach. Ultimately, the goal of the program is to allow care teams to achieve the triple aim of improving the patient experience, improving clinical outcomes, and reducing the total cost of health care.
STUDY DESIGN
This is a retrospective examination of the first year of the Shared Patient Care Coordination (SPCC) program.
METHODS
The analysis consisted of 2 parts. First, rates of hospitalizations and emergency department visits were compared between the SPCC patients and other patients of the integrated health system who had ESKD but did not participate in SPCC. Second, rates of clinical indicators-central venous catheter (CVC) use, home dialysis, advance care planning, and missed dialysis treatments-were benchmarked vs normative data taken by bootstrap sampling of the kidney care organization's patient population.
RESULTS
Overall, dialysis patients participating in the SPCC program had a 15% lower rate of hospital admissions than those not participating ( P = .02). Additionally, the bootstrap analysis showed that by the second year, dialysis patients in the program had favorable rates (above the 95th percentile) of CVC use, dialysis treatment absenteeism, and completion of advance care plans.
CONCLUSIONS
Enhanced and structured communication between dialysis providers and patient care teams provides a unique opportunity to coordinate patient-centered care and improve patient outcomes.
Topics: Humans; Kidney Failure, Chronic; Retrospective Studies; Male; Female; Middle Aged; Hospitalization; Aged; Accountable Care Organizations; Renal Dialysis; Patient Care Team; Delivery of Health Care, Integrated
PubMed: 38748917
DOI: 10.37765/ajmc.2024.89544 -
STAR Protocols May 2024Single-cell RNA sequencing (scRNA-seq) provides high resolution of cell-to-cell variation in gene expression and offers insights into cell heterogeneity, differentiating...
Single-cell RNA sequencing (scRNA-seq) provides high resolution of cell-to-cell variation in gene expression and offers insights into cell heterogeneity, differentiating dynamics, and disease mechanisms. However, technical challenges such as low capture rates and dropout events can introduce noise in data analysis. Here, we present a deep learning framework, called the dynamic batching adversarial autoencoder (DB-AAE), for denoising scRNA-seq datasets. First, we describe steps to set up the computing environment, training, and tuning. Then, we depict the visualization of the denoising results. For complete details on the use and execution of this protocol, please refer to Ko et al..
PubMed: 38748883
DOI: 10.1016/j.xpro.2024.103067 -
Cell Reports May 2024Amyotrophic lateral sclerosis can be caused by abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the cytoplasm of neurons. Here, we use a C. elegans model...
Amyotrophic lateral sclerosis can be caused by abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the cytoplasm of neurons. Here, we use a C. elegans model for TDP-43-induced toxicity to identify the biological mechanisms that lead to disease-related phenotypes. By applying deep behavioral phenotyping and subsequent dissection of the neuromuscular circuit, we show that TDP-43 worms have profound defects in GABA neurons. Moreover, acetylcholine neurons appear functionally silenced. Enhancing functional output of repressed acetylcholine neurons at the level of, among others, G-protein-coupled receptors restores neurotransmission, but inefficiently rescues locomotion. Rebalancing the excitatory-to-inhibitory ratio in the neuromuscular system by simultaneous stimulation of the affected GABA- and acetylcholine neurons, however, not only synergizes the effects of boosting individual neurotransmitter systems, but instantaneously improves movement. Our results suggest that interventions accounting for the altered connectome may be more efficient in restoring motor function than those solely focusing on diseased neuron populations.
PubMed: 38748878
DOI: 10.1016/j.celrep.2024.114204 -
Cell Reports May 2024ZBP1 is an interferon (IFN)-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA) to promote cell death and inflammation. However, the mechanisms that...
ZBP1 is an interferon (IFN)-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA) to promote cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here, we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppressor of the inflammatory signaling mediated by full-length ZBP1. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z-NA for Zα domains of ZBP1. Cells from mice (Ripk1) with cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-dependent cell death. Intriguingly, Ripk1 cells die spontaneously when ZBP1-S is deleted, indicating that cell death driven by ZBP1 is under the control of ZBP1-S. Thus, our findings reveal that alternative splicing of Zbp1 represents autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z-NA with ZBP1 could be an effective strategy against autoinflammations.
PubMed: 38748877
DOI: 10.1016/j.celrep.2024.114221 -
Cell Reports May 2024Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we...
Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3' UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3' UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.
PubMed: 38748875
DOI: 10.1016/j.celrep.2024.114238