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The Oncologist Nov 2021Although balancing treatment efficacy with risks of complications is critical for older adults with aggressive non-Hodgkin lymphoma (NHL), few studies have described...
BACKGROUND
Although balancing treatment efficacy with risks of complications is critical for older adults with aggressive non-Hodgkin lymphoma (NHL), few studies have described these patients' clinical outcomes, rates of toxicities, and health care utilization.
METHODS
We conducted a retrospective analysis of adults ≥65 years diagnosed with aggressive NHL and receiving systemic therapy at Massachusetts General Hospital from April 2000 to July 2020. We abstracted patient characteristics, clinical outcomes, treatment toxicity, unplanned hospitalizations, and intensive care unit (ICU) admissions within 6 months of treatment initiation from the medical record. Using multivariable logistic regression, we examined factors associated with rates of grade 3+ nonhematologic toxicity and unplanned hospitalization.
RESULTS
Among 295 patients (median age, 73 years; 39.0% female), 5-year overall survival (OS) was 74.2%. Five-year OS by age group (65-69, 70-74, 75-79, and 80+ years) was 82.2%, 72.0%, 73.6%, and 66.4%, respectively. Overall, 42.4% experienced grade 3+ toxicity, with 8.1% experiencing grades 4-5. The rates of unplanned hospitalization and ICU admission were 41.0% and 6.1%, respectively. In multivariable analysis, hypoalbuminemia (odds ratio [OR], 4.29; p < .001) and high comorbidity score (OR, 4.22; p < .001) were associated with likelihood of grade 3+ toxicity. Hypoalbuminemia (OR, 2.83; p = .003), high comorbidity score (OR, 3.93; p = .001), and receipt of EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin; OR, 5.45; p = .012) were associated with likelihood of unplanned hospitalization.
CONCLUSIONS
The majority of older adults receiving upfront therapy for aggressive NHL survive beyond 5 years, yet nearly half experience substantial treatment toxicities and unplanned hospitalizations. Our findings underscore the need for supportive care interventions to enhance the care experience of this population.
IMPLICATIONS FOR PRACTICE
The results of this study highlight the potential benefits of intensive chemoimmunotherapy for the majority of older adults with aggressive non-Hodgkin lymphoma, even at advanced ages. Nearly half of older adults experienced substantial treatment toxicities and unplanned hospitalizations, emphasizing the unmet need for supportive care interventions in this population. The present study also identified hypoalbuminemia and patient comorbidity score as factors associated with grade 3+ nonhematologic toxicity and unplanned hospitalization. These findings may guide the development and implementation of targeted supportive care interventions in high-risk older adults with aggressive non-Hodgkin lymphoma.
Topics: Aged; Female; Hospitalization; Humans; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Male; Patient Acceptance of Health Care; Retrospective Studies
PubMed: 34327767
DOI: 10.1002/onco.13915 -
Cells Oct 2020A new epoch is emerging with intense research on nutraceuticals, i.e., "food or food product that provides medical or health benefits including the prevention and... (Review)
Review
A new epoch is emerging with intense research on nutraceuticals, i.e., "food or food product that provides medical or health benefits including the prevention and treatment of diseases", such as Alzheimer's disease. Nutraceuticals act at different biochemical and metabolic levels and much evidence shows their neuroprotective effects; in particular, they are able to provide protection against mitochondrial damage, oxidative stress, toxicity of β-amyloid and Tau and cell death. They have been shown to influence the composition of the intestinal microbiota significantly contributing to the discovery that differential microorganisms composition is associated with the formation and aggregation of cerebral toxic proteins. Further, the routes of interaction between epigenetic mechanisms and the microbiota-gut-brain axis have been elucidated, thus establishing a modulatory role of diet-induced epigenetic changes of gut microbiota in shaping the brain. This review examines recent scientific literature addressing the beneficial effects of some natural products for which mechanistic evidence to prevent or slowdown AD are available. Even if the road is still long, the results are already exceptional.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Biological Products; Biomarkers; Brain; DNA Methylation; Diet Therapy; Dietary Supplements; Disease Management; Disease Susceptibility; Functional Food; Gastrointestinal Microbiome; Gene Expression Regulation; Humans; Mitochondria; Neuroprotective Agents
PubMed: 33114170
DOI: 10.3390/cells9112347 -
Acta Neurologica Belgica Oct 2021A worldwide decline in stroke hospitalizations during the COVID-19 pandemic has been reported. Information on stroke care during the pandemic in Belgium is lacking. This...
A worldwide decline in stroke hospitalizations during the COVID-19 pandemic has been reported. Information on stroke care during the pandemic in Belgium is lacking. This study aims to analyze the impact of COVID-19 on acute stroke care in eight Belgian stroke centers. This Belgian study is part of an international observational and retrospective study in 70 countries and 457 stroke centers. We compared volumes of COVID-19 and stroke hospitalizations, intravenous thrombolysis and endovascular treatment rates, acute treatment time intervals and functional outcome at 90 days during the first wave of the pandemic to two control intervals (March-May 2019 and December-February 2020). From March 2020 to May 2020, 860 stroke patients were hospitalized. In the same time period, 2850 COVID-19 patients were admitted, of which 37 (1.3%) were diagnosed with a stroke. Compared to the months prior to the pandemic and the same time epoch one year earlier, stroke hospitalizations were reduced (relative difference 15.9% [p = 0.03] and 14.5% [p = 0.05], respectively). Despite a reduction in absolute volumes, there was no difference in the monthly proportion of thrombolysis or endovascular treatment provided to the overall stroke hospitalizations. Acute treatment time metrics did not change between COVID-19 pandemic and control time epochs. We found no difference in 90-day functional outcomes nor in mortality after stroke between patients admitted during the pandemic versus control periods. We found a decline in the volume of stroke hospitalizations during the first wave of the COVID-19 pandemic in Belgium. Stroke care quality parameters remained unchanged.
Topics: Belgium; COVID-19; Humans; SARS-CoV-2; Stroke
PubMed: 34148220
DOI: 10.1007/s13760-021-01726-x -
Stroke Dec 2023The Stroke Treatment Academic Industry Roundtable XII included a workshop to discuss the most promising approaches to improve outcome from acute stroke. The workshop... (Review)
Review
The Stroke Treatment Academic Industry Roundtable XII included a workshop to discuss the most promising approaches to improve outcome from acute stroke. The workshop brought together representatives from academia, industry, and government representatives. The discussion examined approaches in 4 epochs: pre-reperfusion, reperfusion, post-reperfusion, and access to acute stroke interventions. The participants identified areas of priority for developing new and existing treatments and approaches to improve stroke outcomes. Although many advances in acute stroke therapy have been achieved, more work is necessary for reperfusion therapies to benefit the most possible patients. Prioritization of promising approaches should help guide the use of resources and investigator efforts.
Topics: Humans; Brain Ischemia; Thrombolytic Therapy; Stroke; Thrombectomy; Reperfusion; Treatment Outcome
PubMed: 37886850
DOI: 10.1161/STROKEAHA.123.044279 -
JAMA Network Open Apr 2023Evidence on the effectiveness and safety of COVID-19 therapies across a diverse population with varied risk factors is needed to inform clinical practice.
IMPORTANCE
Evidence on the effectiveness and safety of COVID-19 therapies across a diverse population with varied risk factors is needed to inform clinical practice.
OBJECTIVE
To assess the safety of neutralizing monoclonal antibodies (nMAbs) for the treatment of COVID-19 and their association with adverse outcomes.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included 167 183 patients from a consortium of 4 health care systems based in California, Minnesota, Texas, and Utah. The study included nonhospitalized patients 12 years and older with a positive COVID-19 laboratory test collected between November 9, 2020, and January 31, 2022, who met at least 1 emergency use authorization criterion for risk of a poor outcome.
EXPOSURE
Four nMAb products (bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab) administered in the outpatient setting.
MAIN OUTCOMES AND MEASURES
Clinical and SARS-CoV-2 genomic sequence data and propensity-adjusted marginal structural models were used to assess the association between treatment with nMAbs and 4 outcomes: all-cause emergency department (ED) visits, hospitalization, death, and a composite of hospitalization or death within 14 days and 30 days of the index date (defined as the date of the first positive COVID-19 test or the date of referral). Patient index dates were categorized into 4 variant epochs: pre-Delta (November 9, 2020, to June 30, 2021), Delta (July 1 to November 30, 2021), Delta and Omicron BA.1 (December 1 to 31, 2021), and Omicron BA.1 (January 1 to 31, 2022).
RESULTS
Among 167 183 patients, the mean (SD) age was 47.0 (18.5) years; 95 669 patients (57.2%) were female at birth, 139 379 (83.4%) were White, and 138 900 (83.1%) were non-Hispanic. A total of 25 241 patients received treatment with nMAbs. Treatment with nMAbs was associated with lower odds of ED visits within 14 days (odds ratio [OR], 0.76; 95% CI, 0.68-0.85), hospitalization within 14 days (OR, 0.52; 95% CI, 0.45-0.59), and death within 30 days (OR, 0.14; 95% CI, 0.10-0.20). The association between nMAbs and reduced risk of hospitalization was stronger in unvaccinated patients (14-day hospitalization: OR, 0.51; 95% CI, 0.44-0.59), and the associations with hospitalization and death were stronger in immunocompromised patients (hospitalization within 14 days: OR, 0.31 [95% CI, 0.24-0.41]; death within 30 days: OR, 0.13 [95% CI, 0.06-0.27]). The strength of associations of nMAbs increased incrementally among patients with a greater probability of poor outcomes; for example, the ORs for hospitalization within 14 days were 0.58 (95% CI, 0.48-0.72) among those in the third (moderate) risk stratum and 0.41 (95% CI, 0.32-0.53) among those in the fifth (highest) risk stratum. The association of nMAb treatment with reduced risk of hospitalizations within 14 days was strongest during the Delta variant epoch (OR, 0.37; 95% CI, 0.31-0.43) but not during the Omicron BA.1 epoch (OR, 1.29; 95% CI, 0.68-2.47). These findings were corroborated in the subset of patients with viral genomic data. Treatment with nMAbs was associated with a significant mortality benefit in all variant epochs (pre-Delta: OR, 0.16 [95% CI, 0.08-0.33]; Delta: OR, 0.14 [95% CI, 0.09-0.22]; Delta and Omicron BA.1: OR, 0.10 [95% CI, 0.03-0.35]; and Omicron BA.1: OR, 0.13 [95% CI, 0.02-0.93]). Potential adverse drug events were identified in 38 treated patients (0.2%).
CONCLUSIONS AND RELEVANCE
In this study, nMAb treatment for COVID-19 was safe and associated with reductions in ED visits, hospitalization, and death, although it was not associated with reduced risk of hospitalization during the Omicron BA.1 epoch. These findings suggest that targeted risk stratification strategies may help optimize future nMAb treatment decisions.
Topics: Infant, Newborn; Humans; Female; Middle Aged; Male; COVID-19; SARS-CoV-2; Retrospective Studies; Antibodies, Monoclonal
PubMed: 37093599
DOI: 10.1001/jamanetworkopen.2023.9694 -
Journal of Biomedical Physics &... Dec 2022Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adults and its early detection is effective in the successful...
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adults and its early detection is effective in the successful treatment of children. Electroencephalography (EEG) has been widely used for classifying ADHD and normal children. In recent years, deep learning leads to more accurate classification.
OBJECTIVE
This study aims to adapt convolutional neural networks (CNNs) for classifying ADHD and normal children based on the connectivity measure of their EEG signals.
MATERIAL AND METHODS
In this experimental study, the dataset consisted of 61 ADHD and 60 normal children from which 13021 epochs were extracted as input for model training and evaluation. Synchronization likelihood (SL) and wavelet coherence (WC) were considered connectivity measures. The neighborhood between EEG channels was arranged in a two-dimensional matrix for better representation. Four-dimensional (4D) and six-dimensional (6D) connectivity tensors were composed as model inputs. Two architectures were developed, one 4D and 6D CNN for SL and WC-based diagnosis of ADHD, respectively.
RESULTS
A 5-fold cross-validation was utilized to assess developed models. The average accuracy of 98.56% for 4D CNN and 98.85% for 6D CNN in epoch-based classification were obtained. In the case of subject-based classification, the accuracy was 99.17% for both models.
CONCLUSION
Based on the evaluation metrics of the proposed models, ADHD children can be diagnosed and ADHD and normal children can be successfully distinguished.
PubMed: 36569562
DOI: 10.31661/jbpe.v0i0.2108-1380 -
Epilepsia Oct 2021There is a paucity of data to guide anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) with brain sensing. The clinical Medtronic Percept DBS device...
There is a paucity of data to guide anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) with brain sensing. The clinical Medtronic Percept DBS device provides constrained brain sensing power within a frequency band (power-in-band [PIB]), recorded in 10-min averaged increments. Here, four patients with temporal lobe epilepsy were implanted with an investigational device providing full bandwidth chronic intracranial electroencephalogram (cEEG) from bilateral ANT and hippocampus (Hc). ANT PIB-based seizure detection was assessed. Detection parameters were cEEG PIB center frequency, bandwidth, and epoch duration. Performance was evaluated against epileptologist-confirmed Hc seizures, and assessed by area under the precision-recall curve (PR-AUC). Data included 99 days of cEEG, and 20, 278, 3, and 18 Hc seizures for Subjects 1-4. The best detector had 7-Hz center frequency, 5-Hz band width, and 10-s epoch duration (group PR-AUC = .90), with 75% sensitivity and .38 false alarms per day for Subject 1, and 100% and .0 for Subjects 3 and 4. Hc seizures in Subject 2 did not propagate to ANT. The relative change of ANT PIB was maximal ipsilateral to seizure onset for all detected seizures. Chronic ANT and Hc recordings provide direct guidance for ANT DBS with brain sensing.
Topics: Anterior Thalamic Nuclei; Deep Brain Stimulation; Epilepsy; Hippocampus; Humans; Seizures; Thalamus
PubMed: 34418083
DOI: 10.1111/epi.17047 -
Journal of Clinical and Experimental... 2023CD5-positive diffuse large B cell lymphoma (CD5+ DLBCL) is a high-risk lymphoma type. Recently, the PEARL5 (a Phase II trial of DA-EPOCH and Rituximab with HD-MTX...
CD5-positive diffuse large B cell lymphoma (CD5+ DLBCL) is a high-risk lymphoma type. Recently, the PEARL5 (a Phase II trial of DA-EPOCH and Rituximab with HD-MTX therapy for newly diagnosed DLBCL with CD5 expression) study demonstrated the efficacy of the DA-EPOCH-R (cyclophosphamide, etoposide, doxorubicin, vincristine, prednisone, and rituximab)/HD-MTX (high-dose methotrexate) regimen for CD5+ DLBCL. In this report, we revealed the impact of the DA-EPOCH-R/HD-MTX regimen on the clinical course of CD5+ DLBCL in the real-world. We retrospectively compared CD5+ and CD5- DLBCL patients diagnosed from January 2017 to December 2020 and analyzed their clinicopathological characteristics, treatment, and prognosis. There was no difference in age, sex, clinical stage, and cell of origin; however, the CD5-positive group had higher lactate dehydrogenase levels and a worse performance status than the CD5-negative group (p=0.00121 and p=0.0378, respectively). International prognostic index (IPI) was worse in the CD5-positive group than in the CD5-negative group (p=0.0498), but NCCN-IPI (National Comprehensive Cancer Network-IPI) was no different between the two groups. The CD5-positive group was more frequently treated with the DA-EPOCH-R/HD-MTX regimen than the CD5-negative group (p =0.001857). Complete remission rate and 1-year overall survival did not differ between the CD5-positive and -negative groups (90.0% vs 81.4%, p=0.853; 81.8% vs 76.9%, p=0.433). We conclude that the DA-EPOCH-R/HD-MTX regimen is effective for CD5+ DLBCL in this single institute analysis.
Topics: Humans; Rituximab; Prednisone; Etoposide; Vincristine; Retrospective Studies; Methotrexate; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Lymphoma, Large B-Cell, Diffuse
PubMed: 36990773
DOI: 10.3960/jslrt.22035 -
Journal of Pharmacological Sciences 2014Induced pluripotent stem cell (iPSC) generation is an epoch-making technology. The potential applications for iPSCs are wide-ranging from in vitro disease models to drug... (Review)
Review
Induced pluripotent stem cell (iPSC) generation is an epoch-making technology. The potential applications for iPSCs are wide-ranging from in vitro disease models to drug discovery. For regenerative medicine in particular, the technology provides great hope for patients with incurable diseases or potentially fatal disorders such as heart failure (HF). However, the true realization of that promise for HF remains uncertain and moving toward the clinical application of iPSCs needs to be stepwise and careful. The establishment of "safe" iPSCs must be a major premise, while genome integration-free and oncogene-free reprogramming is also necessary. Teratoma formation also remains a risk with undifferentiated iPSCs, but it must not happen in patients' bodies. Thus, regardless of the target organ, the differentiated cells from iPSCs must be purified to exclude any possibility of tumorigenicity. The transplantation strategies used for iPSC-derived cells are very important for the recovery of lost cardiac function. Longer engraftment of transplanted iPSCs-derived cardiomyocytes is essential particularly because their survival could be hampered by ischemia, inflammation, apoptosis, immunological rejection, and other cardiac phenomena. Providing these multistep solutions will open the new frontier of regenerative therapies with iPSCs for patients with severe HF.
Topics: Cell Differentiation; Cell Survival; Cell- and Tissue-Based Therapy; Heart Failure; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Regenerative Medicine; Severity of Illness Index; Stem Cell Transplantation
PubMed: 24739283
DOI: 10.1254/jphs.14r01cp -
Journal of the American College of... Jan 2023Brain injury is common in neonates with complex neonatal congenital heart disease (CHD) and affects neurodevelopmental outcomes.
BACKGROUND
Brain injury is common in neonates with complex neonatal congenital heart disease (CHD) and affects neurodevelopmental outcomes.
OBJECTIVES
Given advancements in perioperative care, we sought to determine if the rate of preoperative and postoperative brain injury detected by using brain magnetic resonance imaging (MRI) and associated clinical risk factors have changed over time in complex CHD.
METHODS
A total of 270 term newborns with complex CHD were prospectively enrolled for preoperative and postoperative brain MRIs between 2001 and 2021 with a total of 466 MRI scans. Brain injuries in the form of white matter injury (WMI) or focal stroke and clinical factors were compared across 4 epochs of 5-year intervals with logistic regression.
RESULTS
Rates of preoperative WMI and stroke did not change over time. After adjusting for timing of the postoperative MRI, site, and cardiac group, the odds of newly acquired postoperative WMI were significantly lower in Epoch 4 compared with Epoch 1 (OR: 0.29; 95% CI: 0.09-1.00; P = 0.05). The adjusted probability of postoperative WMI declined significantly by 18.7% from Epoch 1 (24%) to Epoch 4 (6%). Among clinical risk factors, lowest systolic, mean, and diastolic blood pressures in the first 24 hours after surgery were significantly higher in the most recent epoch.
CONCLUSIONS
The prevalence of postoperative WMI has declined, whereas preoperative WMI rates remain constant. More robust postoperative blood pressures may explain these findings by minimizing periods of ischemia and supporting cerebral perfusion. These results suggest potential modifiable clinical targets in the postoperative time period to minimize the burden of WMI.
Topics: Humans; Infant, Newborn; Brain Injuries; Heart Defects, Congenital; Incidence; Magnetic Resonance Imaging; Stroke; Postoperative Complications
PubMed: 36653093
DOI: 10.1016/j.jacc.2022.10.029