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Alzheimer's & Dementia : the Journal of... Feb 2024Few studies have examined the associations of psychosocial factors with cognitive change in Hispanics/Latinos.
Psychosocial factors associated with 7-year change in cognition among middle-aged and older Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) and Sociocultural ancillary studies.
INTRODUCTION
Few studies have examined the associations of psychosocial factors with cognitive change in Hispanics/Latinos.
METHODS
Data from the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL INCA) and Sociocultural studies were used (n = 2,155; ages ≥45 years). Psychosocial exposures included intrapersonal (ethnic identity, optimism, purpose in life), interpersonal (family cohesion, familism, social networks, social support), and social factors (ethnic discrimination, loneliness, subjective social status). Survey-linear regression models examined associations between psychosocial exposures and 7-year cognitive change (global cognition [GC], verbal learning, memory, word fluency [WF], and digit symbol substitution [DSS]).
RESULTS
Familism predicted decline in GC, verbal learning, and memory; family cohesion predicted DSS decline; and loneliness predicted memory decline. Ethnic identity was protective against decline in GC and memory, optimism and social support were protective against decline in memory, and purpose in life was protective against WF decline.
DISCUSSION
Psychosocial factors are differentially related to cognitive changes. Culturally relevant factors should be explored in Hispanic/Latino cognitive aging research.
HIGHLIGHTS
Psychosocial factors are differentially related to cognitive changes in Latinos. Role of culturally relevant factors on cognition should be further explored. Familism predicted decline in global cognition, verbal learning, and memory. Ethnic identity predicted increase in global cognition and memory.
Topics: Aged; Humans; Middle Aged; Aging; Cognition; Hispanic or Latino; Public Health; Surveys and Questionnaires; Psychology
PubMed: 37897802
DOI: 10.1002/alz.13527 -
Journal of the American Geriatrics... Sep 2023Retirement represents a crucial transitional period for many adults with possible consequences for cognitive aging. We examined trajectories of cognitive change before...
BACKGROUND
Retirement represents a crucial transitional period for many adults with possible consequences for cognitive aging. We examined trajectories of cognitive change before and after retirement in Black and White adults.
METHODS
Longitudinal examination of up to 10 years (mean = 7.1 ± 2.2 years) using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study-a national, longitudinal study of Black and White adults ≥45 years of age. Data were from 2226 members of the REGARDS study who retired around the time when an occupational ancillary survey was administered. Cognitive function was an average of z-scores for tests of verbal fluency, memory, and global function.
RESULTS
Cognitive functioning was stable before retirement (Estimate = 0.05, p = 0.322), followed by a significant decline after retirement (Estimate = -0.15, p < 0.001). The decline was particularly pronounced in White (Estimate = -0.19, p < 0.001) compared with Black (Estimate = -0.07, p = 0.077) participants, twice as large in men (Estimate = -0.20, p < 0.001) compared with women (Estimate = -0.11, p < 0.001), highest among White men (Estimate = -0.22, p < 0.001) and lowest in Black women (Estimate = -0.04, p = 0.457). Greater post-retirement cognitive decline was also observed among participants who attended college (Estimate = -0.14, p = 0.016). While greater work complexity (Estimate = 0.92, p < 0.05) and higher income (Estimate = 1.03, p < 0.05) were related to better cognitive function at retirement, neither was significantly related to cognitive change after retirement.
CONCLUSION
Cognitive functioning may decline at an accelerated rate immediately post-retirement, more so in White adults and men than Black adults and women. Lifelong structural inequalities including occupational segregation and other social determinants of cognitive health may obscure the role of retirement in cognitive aging.
Topics: Male; Humans; Female; Aged; Retirement; Cognitive Aging; Longitudinal Studies; Cognition; Cognitive Dysfunction; Aging
PubMed: 37465869
DOI: 10.1111/jgs.18475 -
American Journal of Clinical Pathology Apr 2024Systemic mastocytosis (SM) is a neoplasm of mast cells (MCs) characterized by their proliferation in extracutaneous organs. Systemic mastocytosis includes several...
OBJECTIVES
Systemic mastocytosis (SM) is a neoplasm of mast cells (MCs) characterized by their proliferation in extracutaneous organs. Systemic mastocytosis includes several entities with different clinical courses and prognoses. The rarity of this disease and the diversity of clinical and morphologic presentation make the diagnosis of SM very challenging. The aim of this review is to share our approach to the diagnosis of SM.
METHODS
We present 4 cases that highlight the spectrum of clinical and laboratory features of SM and outline the diagnostic process with an emphasis on morphology.
RESULTS
Pathology and laboratory medicine play a key role in investigation of SM, as correct diagnosis requires integration of morphologic, molecular, and serologic findings. In addition to awareness of microscopic findings in SM, a pathologist must keep abreast with an expanding menu of ancillary studies, particularly molecular testing.
CONCLUSIONS
Systemic mastocytosis is a challenging diagnosis that requires not only a demonstration of a clonal proliferation of MCs but also a correct subclassification based on the recently updated criteria.
PubMed: 38683762
DOI: 10.1093/ajcp/aqae047 -
JAMA Ophthalmology Nov 2023The identification of patients at risk of progressing from intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) is essential for clinical...
IMPORTANCE
The identification of patients at risk of progressing from intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) is essential for clinical trials aimed at preventing disease progression. DeepGAze is a fully automated and accurate convolutional neural network-based deep learning algorithm for predicting progression from iAMD to GA within 1 year from spectral-domain optical coherence tomography (SD-OCT) scans.
OBJECTIVE
To develop a deep-learning algorithm based on volumetric SD-OCT scans to predict the progression from iAMD to GA during the year following the scan.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included participants with iAMD at baseline and who either progressed or did not progress to GA within the subsequent 13 months. Participants were included from centers in 4 US states. Data set 1 included patients from the Age-Related Eye Disease Study 2 AREDS2 (Ancillary Spectral-Domain Optical Coherence Tomography) A2A study (July 2008 to August 2015). Data sets 2 and 3 included patients with imaging taken in routine clinical care at a tertiary referral center and associated satellites between January 2013 and January 2023. The stored imaging data were retrieved for the purpose of this study from July 1, 2022, to February 1, 2023. Data were analyzed from May 2021 to July 2023.
EXPOSURE
A position-aware convolutional neural network with proactive pseudointervention was trained and cross-validated on Bioptigen SD-OCT volumes (data set 1) and validated on 2 external data sets comprising Heidelberg Spectralis SD-OCT scans (data sets 2 and 3).
MAIN OUTCOMES AND MEASURES
Prediction of progression to GA within 13 months was evaluated with area under the receiver-operator characteristic curves (AUROC) as well as area under the precision-recall curve (AUPRC), sensitivity, specificity, positive predictive value, negative predictive value, and accuracy.
RESULTS
The study included a total of 417 patients: 316 in data set 1 (mean [SD] age, 74 [8]; 185 [59%] female), 53 in data set 2, (mean [SD] age, 83 [8]; 32 [60%] female), and 48 in data set 3 (mean [SD] age, 81 [8]; 32 [67%] female). The AUROC for prediction of progression from iAMD to GA within 1 year was 0.94 (95% CI, 0.92-0.95; AUPRC, 0.90 [95% CI, 0.85-0.95]; sensitivity, 0.88 [95% CI, 0.84-0.92]; specificity, 0.90 [95% CI, 0.87-0.92]) for data set 1. The addition of expert-annotated SD-OCT features to the model resulted in no improvement compared to the fully autonomous model (AUROC, 0.95; 95% CI, 0.92-0.95; P = .19). On an independent validation data set (data set 2), the model predicted progression to GA with an AUROC of 0.94 (95% CI, 0.91-0.96; AUPRC, 0.92 [0.89-0.94]; sensitivity, 0.91 [95% CI, 0.74-0.98]; specificity, 0.80 [95% CI, 0.63-0.91]). At a high-specificity operating point, simulated clinical trial recruitment was enriched for patients progressing to GA within 1 year by 8.3- to 20.7-fold (data sets 2 and 3).
CONCLUSIONS AND RELEVANCE
The fully automated, position-aware deep-learning algorithm assessed in this study successfully predicted progression from iAMD to GA over a clinically meaningful time frame. The ability to predict imminent GA progression could facilitate clinical trials aimed at preventing the condition and could guide clinical decision-making regarding screening frequency or treatment initiation.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Algorithms; Deep Learning; Disease Progression; Geographic Atrophy; Macular Degeneration; Retrospective Studies; Tomography, Optical Coherence; Clinical Trials as Topic
PubMed: 37856139
DOI: 10.1001/jamaophthalmol.2023.4659 -
Experimental and Clinical... Apr 2024Brain death is defined as the complete and irreversible cessation of the entire brain function, including the brainstem. For the most part, the diagnosis is clinical,... (Review)
Review
Brain death is defined as the complete and irreversible cessation of the entire brain function, including the brainstem. For the most part, the diagnosis is clinical, and ancillary testing is only needed when clinical criteria are not satisfied. Differences exist in brain death diagnosis policy in the confirmation of brain death with ancillary testing and the particular test used. Demonstration of the absence of cerebral circulation is a reliable indicator of brain death. Currently, there are no agreed-on universal criteria for ancillary imaging investigation. However, several guidelines and meta-analyses have referred to radionuclide imaging as the most reliable, accurate, and validated ancillary imaging procedure in the confirmation of brain death. Whenever available, lipophilic agents should be preferred using tomographic imaging in all or as needed. False results may occur because of slight temporal delays in flow-function interaction, and such findings may carry prognostic information. Detectable cerebral circulation in the clinical presence of brain death most probably indicates that the process of dying is not yet complete. The results of radionuclide studies may also suggest that the loss of viability in a significant proportion of brain tissue is not compatible with life.
Topics: Brain Death; Humans; Predictive Value of Tests; Cerebrovascular Circulation; Brain; Radiopharmaceuticals; Reproducibility of Results; Perfusion Imaging; Prognosis
PubMed: 38775696
DOI: 10.6002/ect.BDCDSymp.L15 -
Cureus Sep 2023Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder of the mature B-cells, mostly seen in men, and is characterized by cytopenia, splenomegaly,...
INTRODUCTION
Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder of the mature B-cells, mostly seen in men, and is characterized by cytopenia, splenomegaly, myelofibrosis, and the presence of atypical lymphoid cells showing the cytoplasmic hairy projection in the peripheral blood, bone marrow, and spleen. The immunophenotypic (IPT) profile shows the clonal expansion of B-cells with CD19, CD20, and CD22 showing bright expression. The diagnosis requires two hairy cell markers out of CD103, CD123, CD25, and CD11c to be positive. The HCL variant (HCL-v) has a different IPT profile with negative CD25 in most cases.
AIM
The aim was to study the hematological and IPT of classical HCL and HCL variants.
METHODS
This cross-sectional study included all the cases of HCL diagnosed over a retrospective period of eight years from 1st January 2015 to 31st December 2022 in a tertiary care hospital in north India. The patients included in the study were those for whom immunophenotyping; that is, flow cytometry and/or immunohistochemistry (IHC) were done for diagnosis. Bone marrow slides, IHC slides, and flow cytometric IPTs were reviewed.
RESULTS
The study included 13 patients who were diagnosed to have HCL, of which 12 were classical HCL and one was HCL-variant (HCL-v). Among classical HCL, IPT was done by flow cytometry in 10 patients, while in two patients, it was done by IHC. CD19, CD20, and CD22 were positive in all patients of classical HCL (10/10, 10/10, and 5/5, respectively), while CD123, CD103, CD25, and CD11C were positive in 100%, 89%, 80%, and 100% cases, respectively. One patient of HCL-v had CD103 and CD123 positive, while CD25 and CD123 were negative.
CONCLUSION
The diagnosis of HCL requires a multipronged approach. The use of clinical features, morphology, and immunophenotyping combined with ancillary techniques provides higher diagnostic accuracy and enables its distinction from other B-cell lymphoproliferative disorders (BCLPDs), leading to better patient management and treatment.
PubMed: 37814728
DOI: 10.7759/cureus.44876 -
Journal of Cardiovascular Development... Sep 2023Dramatic advances in the management of congenital heart disease (CHD) have improved survival to adulthood from less than 10% in the 1960s to over 90% in the current era,...
Design and Harmonization Approach for the Multi-Institutional Neurocognitive Discovery Study (MINDS) of Adult Congenital Heart Disease (ACHD) Neuroimaging Ancillary Study: A Technical Note.
Dramatic advances in the management of congenital heart disease (CHD) have improved survival to adulthood from less than 10% in the 1960s to over 90% in the current era, such that adult CHD (ACHD) patients now outnumber their pediatric counterparts. ACHD patients demonstrate domain-specific neurocognitive deficits associated with reduced quality of life that include deficits in educational attainment and social interaction. Our hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits modified by behavioral and environmental enrichment proxies of cognitive reserve (e.g., level of education and lifestyle/social habits). This technical note describes an ancillary study to the National Heart, Lung, and Blood Institute (NHLBI)-funded Pediatric Heart Network (PHN) "Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD)". Leveraging clinical, neuropsychological, and biospecimen data from the parent study, our study will provide structural-physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging initiative to be performed in ACHD patients. Limitations of the study include recruitment challenges inherent to an ancillary study, implantable cardiac devices, and harmonization of neuroimaging biomarkers. Results from this research will help shape the care of ACHD patients and further our understanding of the interplay between brain injury and cognitive reserve.
PubMed: 37754810
DOI: 10.3390/jcdd10090381 -
Advances in Anatomic Pathology Nov 2023This article reviewed the identification of breast cancer in the distant metastatic setting through traditional immunohistochemical markers, such as mammaglobin and...
This article reviewed the identification of breast cancer in the distant metastatic setting through traditional immunohistochemical markers, such as mammaglobin and GATA3, compared with the novel immunohistochemical stain, Trichorhinophalangeal syndrome-1 (TRPS1). We review previous studies evaluating TRPS1 staining, which were conducted using cytology specimens, as well as our recently conducted study evaluating this stain using surgical tissue samples, both from primary and distant metastatic invasive breast carcinoma. In summary, although no immunohistochemical stain is 100% specific or sensitive, in the metastatic setting where tissue available for ancillary studies is limited, TRPS1 was a reliable and even a standalone marker for breast origin, particularly in cases of triple-negative breast cancer.
PubMed: 37593968
DOI: 10.1097/PAP.0000000000000409 -
PloS One 2024Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates...
Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.
OBJECTIVES
Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST.
METHODS/MATERIALS
This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed.
RESULTS
Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4).
CONCLUSIONS
In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.
Topics: Humans; Female; Endometrial Neoplasms; Myometrium; Middle Aged; Adult; Republic of Korea; Neoplasm Invasiveness; Neoplasm Grading; Prospective Studies; Aged; Preoperative Period; Magnetic Resonance Imaging; Carcinoma, Endometrioid
PubMed: 38935680
DOI: 10.1371/journal.pone.0305360 -
Journal of Neurology, Neurosurgery, and... Jan 2024Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms....
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in c.778G>A [p.Glu260Lys] manifesting with juvenile ALS.
METHODS
Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients' blood and fibroblasts, was performed.
RESULTS
All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in and -associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS.
CONCLUSIONS
is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further.
Topics: Child; Humans; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Sphingolipids; Serine C-Palmitoyltransferase; Hereditary Sensory and Autonomic Neuropathies; Serine
PubMed: 38041679
DOI: 10.1136/jnnp-2023-332132