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1.
J Am Coll Surg ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023165

RESUMEN

BACKGROUND: Healthcare is responsible for 8.5% of US greenhouse gas emissions. These impacts must be mitigated while maintaining clinical excellence. This study compares clinical outcomes, cost-efficiency, and climate impact of trans-umbilical laparoscopic assisted appendectomy (TULAA) versus 3-port laparoscopic appendectomy (LA). STUDY DESIGN: Institutional Review Board approval was obtained. Appendectomies performed between Jan 1, 2020 and December 31, 2022 at a tertiary children's hospital were reviewed. Data abstracted included clinical characteristics, operative approach and findings, supplies and equipment utilized, and complications. For analysis TULAA was combined with cases converted to LA (TULAA+C). To determine a surgical site infection (SSI) increase of ≤ 2.5%, a minimum sample size of 479 patients per group was needed to achieve a power of 80%. A composite supply list for each approach was determined by averaging supplies from cases reviewed. The composite was used to calculate cost-efficiency and climate impact. Life cycle assessment was used to determine the carbon footprint (according to ISO 14067) of supplies and equipment. RESULTS: Analysis was performed on 1,611 appendectomies: 497 LA and 1,114 TULAA+C (932 TULAA, 182 converted). Except for BMI, there were no clinically significant differences between groups. SSI did not increase with TULAA+C (n=15, 1.3%) versus LA (n=6, 1.2%), p=0.81. TULAA+C ($369.21/case) was more cost efficient than LA ($879.30/case) and TULAA+C (24.8 kg CO2e) produced fewer emissions than LA (27.4 kg CO2e). CONCLUSIONS: While patient safety and excellent clinical outcomes must remain the top priority in healthcare, the current environmental crisis demands consideration of climate impacts. When clinical non-inferiority can be demonstrated, treatment options with a fewer greenhouse gas emissions should be chosen.

2.
JAMA ; 331(12): 1035-1044, 2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38530261

RESUMEN

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.


Asunto(s)
Hernia Inguinal , Herniorrafia , Recien Nacido Prematuro , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Asiático/estadística & datos numéricos , Teorema de Bayes , Edad Gestacional , Hernia Inguinal/epidemiología , Hernia Inguinal/etnología , Hernia Inguinal/cirugía , Herniorrafia/efectos adversos , Herniorrafia/métodos , Herniorrafia/estadística & datos numéricos , Alta del Paciente , Factores de Edad , Hispánicos o Latinos/estadística & datos numéricos , Blanco/estadística & datos numéricos , Estados Unidos/epidemiología , Negro o Afroamericano/estadística & datos numéricos
3.
Brain ; 147(6): 2158-2168, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38315899

RESUMEN

Vascular dysfunction is increasingly recognized as an important contributor to the pathogenesis of Alzheimer's disease. Alterations in vascular endothelial growth factor (VEGF) pathways have been implicated as potential mechanisms. However, the specific impact of VEGF proteins in preclinical Alzheimer's disease and their relationships with other Alzheimer's disease and vascular pathologies during this critical early period remain to be elucidated. We included 317 older adults from the Harvard Aging Brain Study, a cohort of individuals who were cognitively unimpaired at baseline and followed longitudinally for up to 12 years. Baseline VEGF family protein levels (VEGFA, VEGFC, VEGFD, PGF and FLT1) were measured in fasting plasma using high-sensitivity immunoassays. Using linear mixed effects models, we examined the interactive effects of baseline plasma VEGF proteins and amyloid PET burden (Pittsburgh Compound-B) on longitudinal cognition (Preclinical Alzheimer Cognitive Composite-5). We further investigated if effects on cognition were mediated by early neocortical tau accumulation (flortaucipir PET burden in the inferior temporal cortex) or hippocampal atrophy. Lastly, we examined the impact of adjusting for baseline cardiovascular risk score or white matter hyperintensity volume. Baseline plasma VEGFA and PGF each showed a significant interaction with amyloid burden on prospective cognitive decline. Specifically, low VEGFA and high PGF were associated with greater cognitive decline in individuals with elevated amyloid, i.e. those on the Alzheimer's disease continuum. Concordantly, low VEGFA and high PGF were associated with accelerated longitudinal tau accumulation in those with elevated amyloid. Moderated mediation analyses confirmed that accelerated tau accumulation fully mediated the effects of low VEGFA and partially mediated (31%) the effects of high PGF on faster amyloid-related cognitive decline. The effects of VEGFA and PGF on tau and cognition remained significant after adjusting for cardiovascular risk score or white matter hyperintensity volume. There were concordant but non-significant associations with longitudinal hippocampal atrophy. Together, our findings implicate low VEGFA and high PGF in accelerating early neocortical tau pathology and cognitive decline in preclinical Alzheimer's disease. Additionally, our results underscore the potential of these minimally-invasive plasma biomarkers to inform the risk of Alzheimer's disease progression in the preclinical population. Importantly, VEGFA and PGF appear to capture distinct effects from vascular risks and cerebrovascular injury. This highlights their potential as new therapeutic targets, in combination with anti-amyloid and traditional vascular risk reduction therapies, to slow the trajectory of preclinical Alzheimer's disease and delay or prevent the onset of cognitive decline.


Asunto(s)
Enfermedad de Alzheimer , Cognición , Factor A de Crecimiento Endotelial Vascular , Proteínas tau , Humanos , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Masculino , Femenino , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/metabolismo , Anciano , Proteínas tau/metabolismo , Proteínas tau/sangre , Estudios Longitudinales , Anciano de 80 o más Años , Cognición/fisiología , Tomografía de Emisión de Positrones , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/sangre , Biomarcadores/sangre
4.
JAMA Neurol ; 80(12): 1353-1363, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37843849

RESUMEN

Importance: Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors. Objective: To estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes. Design, Setting, and Participants: This cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers-the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer's Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019). Main Outcome and Measures: The main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH. Results: Data from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = -3.1 [P = .002]; ADNI: t = -5.6 [P < .001]; HABS: t = -2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001). Conclusions and Relevance: The findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.


Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Sustancia Blanca , Humanos , Femenino , Anciano , Adulto , Masculino , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/complicaciones , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Estudios Longitudinales , Estudios de Cohortes , Estudios Transversales , Imagen por Resonancia Magnética , Amiloidosis/complicaciones , Proteínas Amiloidogénicas
5.
Alzheimers Dement (Amst) ; 15(3): e12473, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37693224

RESUMEN

The Face Name Associative Memory Exam (FNAME) was introduced into the NIH Toolbox as part of the ARMADA study and establishes normative data for diverse participants, ages 64 to 85+, and proposes cutoff scores between biomarker positive versus negative (+/-) groups. The FNAME was administered to 257 participants across the clinical spectrum with 122 having amyloid biomarkers. Linear regression explored the association between demographics and FNAME and between amyloid (+/-) groups. Receiver operating characteristic curves (ROC) identified performance thresholds that best discriminated between biomarker (+/-) individuals. Lower FNAME scores occurred in males, older ages, Black/African Americans, Hispanics, and biomarker-positive participants. ROC analyses demonstrated acceptable accuracy (0.73 to 0.77) but only when combined with clinical status. The diagnostic discrimination of amyloid positivity was acceptable but not excellent, suggesting the FNAME may be a better screening indicator of clinical status rather than amyloid deposition in cognitively normal individuals. Normative data are provided.

6.
Aging Cell ; 22(8): e13871, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37291760

RESUMEN

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection of cerebrospinal fluid (CSF) as part of their participation in DIAN were included in this study. Linear mixed effects models were used to determine differences in clinical, cognitive, and biomarker measures between the NC, TM, and CY groups. While both the CY and TM groups were found to have similarly elevated Aß compared to NC, TM carriers had greater cognitive impairment, smaller hippocampal volume, and elevated phosphorylated tau levels across the spectrum of pre-symptomatic and symptomatic phases of disease as compared to CY, using both cross-sectional and longitudinal data. As distinct portions of PSEN1 are differentially involved in APP processing by γ-secretase and the generation of toxic ß-amyloid species, these results have important implications for understanding the pathobiology of ADAD and accounting for a substantial portion of the interindividual heterogeneity in ongoing ADAD clinical trials.


Asunto(s)
Enfermedad de Alzheimer , Presenilina-1 , Humanos , Masculino , Femenino , Adulto , Encéfalo/metabolismo , Encéfalo/patología , Tomografía de Emisión de Positrones , Imagen por Resonancia Magnética , Presenilina-1/química , Presenilina-1/genética , Presenilina-1/metabolismo , Mutación , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Cognición , Péptidos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Estudios Longitudinales , Estudios Transversales , Biomarcadores
7.
J Alzheimers Dis ; 94(1): 217-226, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37212093

RESUMEN

BACKGROUND: Detecting clinically meaningful changes in instrumental activities of daily living (IADL) at the earliest stages of Alzheimer's disease (AD) is critical. OBJECTIVE: The objective of this exploratory study was to examine the cross-sectional relationship between a performance-based IADL test, the Harvard Automated Phone Task (APT), and cerebral tau and amyloid burden in cognitively normal (CN) older adults. METHODS: Seventy-seven CN participants underwent flortaucipir tau and Pittsburgh Compound B amyloid PET. IADL were assessed using the three Harvard APT tasks: prescription refill (APT-Script), health insurance company call (APT-PCP), and bank transaction (APT-Bank). Linear regression models were used to determine associations between each APT task and entorhinal cortex, inferior temporal, or precuneus tau with or without an interaction with amyloid. RESULTS: Significant associations were found between APT-Bank task rate and interaction between amyloid and entorhinal cortex tau, and APT-PCP task and interactions between amyloid and inferior temporal and precuneus tau. No significant associations were found between the APT tasks and tau or amyloid alone. CONCLUSION: Our preliminary findings suggest an association between a simulated real-life IADL test and interactions of amyloid and several regions of early tau accumulation in CN older adults. However, some analyses were underpowered due to the small number of participants with elevated amyloid, and findings should be interpreted with caution. Future studies will further explore these associations cross-sectionally and longitudinally in order to determine whether the Harvard APT can serve as a reliable IADL outcome measure for preclinical AD prevention trials and ultimately in the clinic setting.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Proteínas tau/metabolismo , Actividades Cotidianas , Disfunción Cognitiva/patología , Corteza Entorrinal/patología , Amiloide/metabolismo , Proteínas Amiloidogénicas , Tomografía de Emisión de Positrones , Péptidos beta-Amiloides/metabolismo
8.
J Forensic Sci ; 67(6): 2218-2229, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36059116

RESUMEN

The genealogy process is typically the most time-consuming part of-and a limiting factor in the success of-forensic genetic genealogy, which is a new approach to solving violent crimes and identifying human remains. We formulate a stochastic dynamic program that-given the list of matches and their genetic distances to the unknown target-chooses the best decision at each point in time: which match to investigate (i.e., find its ancestors and look for most recent common ancestors between the match and the target), which set of potential most recent common ancestors to descend from (i.e., find its descendants, with the goal of identifying a marriage between the maternal and paternal sides of the target's family tree), or whether to terminate the investigation. The objective is to maximize the probability of finding the target minus a cost associated with the expected size of the final family tree. We estimate the parameters of our model using data from 17 cases (eight solved, nine unsolved) from the DNA Doe Project. We assess the Proposed Strategy using simulated versions of the 17 DNA Doe Project cases, and compare it to a Benchmark Strategy that ranks matches by their genetic distance to the target and only descends from known common ancestors between a pair of matches. The Proposed Strategy solves cases ≈10 - fold faster than the Benchmark Strategy, and does so by aggressively descending from a set of potential most recent common ancestors between the target and a match even when this set has a low probability of containing the correct most recent common ancestor. Our analysis provides a mathematical foundation for improving the genealogy process in forensic genetic genealogy.


Asunto(s)
ADN , Genética Forense , Humanos , Linaje , ADN/genética , Probabilidad , Modelos Genéticos
9.
J Pediatr Intensive Care ; 11(2): 168-176, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35734211

RESUMEN

Reports of incidental pneumomediastinum in infants secondary to inflicted trauma are limited. A retrospective review of infants with pneumomediastinum and history of inflicted trauma was performed. A comprehensive literature review was performed. Three infants presented with pneumomediastinum associated with inflicted trauma. Mean age was 4.6 weeks. All patients underwent diagnostic studies, as well as a standardized evaluation for nonaccidental trauma. All patients with pneumomediastinum were resolved at follow-up. Review of the literature identified other cases with similar presentations with related oropharyngeal injuries. Spontaneous pneumomediastinum in previously healthy infants may be associated with inflicted injuries. Clinicians should be aware of the possibility of an oropharyngeal perforation related to this presentation.

10.
Pediatr Gastroenterol Hepatol Nutr ; 25(3): 211-217, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35611372

RESUMEN

Purpose: Outcomes between primary gastrostomy tubes and buttons (G-tube and G-button) have not been established in pediatric patients. We hypothesized that primary G-tube have decreased complications when compared to G-button. Methods: A retrospective review of surgically placed gastrostomy devices from 2010 to 2017 was performed. Data collected included demographics, outcomes and 90-day complications. We divided the patients into primary G-tube and primary G-button. Results: Of 265 patients, 142 (53.6%) were male. Median age and weight at the time of surgery were 7 months (interquartile range [IQR], 2-44 months) and 6.70 kg (IQR, 3.98-14.15 kg), respectively. Among the groups, G-tube had 80 patients (30.2%) while G-button 185 patients (69.8%). There were 153 patients with at least one overall complication within 90 days postoperative. There was no significant difference in overall complications between groups (G-tube 63.8% vs. G-button 55.7%, p=0.192). More importantly, there were no significant differences in major complications among the groups, G-tube vs. G-button (5% vs. 4%; p=0.455). Conclusion: Primary G-tube offers no significant advantage in overall, minor or major complications when compared to primary G-button.

11.
Pediatr Surg Int ; 38(6): 891-897, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35396951

RESUMEN

PURPOSE: We aimed to evaluate a complicated appendicitis clinical practice guideline at our institution. METHODS: Records were compared before and after protocol implementation. We standardized an ED consult pathway, antibiotic use and need for early appendectomy (EA) versus interval appendectomy (IA). We evaluated demographics, clinical characteristics, and outcomes. Subgroup analysis was performed to compare patients with small abscess treated with IA pre-protocol versus similar patients treated by EA post-protocol. RESULTS: In total 246 patients were reviewed (Pre-protocol = 152, Post-protocol = 94). Pre-protocol early appendectomy rate was 51% versus 82% on post-protocol patients. There were no differences in demographics. Post-protocol the use of preoperative imaging significantly decreased (Pre 92% vs. 56%, p = 0.0001), as well as the use of discharge antibiotics (Pre 93% vs. Post 27%, p = 0.0001) with no change in abscess rate. Overall, post-protocol patients had fewer total CT scans performed (Pre 40% vs. Post 28%, p = 0.03) and decreased total length of stay (Pre 7.7 vs. Post 6.5 days, p = 0.049). On subgroup analysis, post-protocol EA with no or small abscess had lower median number of admissions, decreased total LOS (Pre IA 9 days vs. Post EA 5 days, p = 0.00001) and fewer complications (Pre IA 42% vs. EA 22%, p = 0.022). CONCLUSION: The establishment of a standardized pediatric complicated appendicitis protocol may lead to improved outcomes and resource utilization. Patients presenting with no or small abscess may be the least likely to benefit from interval appendectomy. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Apendicitis , Absceso/complicaciones , Antibacterianos/uso terapéutico , Apendicectomía/efectos adversos , Apendicitis/complicaciones , Apendicitis/diagnóstico por imagen , Apendicitis/cirugía , Niño , Humanos , Tiempo de Internación , Estudios Retrospectivos
12.
Lancet Neurol ; 21(2): 140-152, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35065037

RESUMEN

BACKGROUND: Insights gained from studying individuals with autosomal dominant Alzheimer's disease have broadly influenced mechanistic hypotheses, biomarker development, and clinical trials in both sporadic and dominantly inherited Alzheimer's disease. Although pathogenic variants causing autosomal dominant Alzheimer's disease are highly penetrant, there is substantial heterogeneity in levels of amyloid ß (Aß) between individuals. We aimed to examine whether this heterogeneity is related to disease progression and to investigate the association with mutation location within PSEN1, PSEN2, or APP. METHODS: We did cross-sectional and longitudinal analyses of data from the Dominantly Inherited Alzheimer's Network (DIAN) observational study, which enrols individuals from families affected by autosomal dominant Alzheimer's disease. 340 participants in the DIAN study who were aged 18 years or older, had a history of autosomal dominant Alzheimer's disease in their family, and who were enrolled between September, 2008, and June, 2019, were included in our analysis. 206 participants were carriers of pathogenic mutations in PSEN1, PSEN2, or APP, and 134 were non-carriers. 62 unique pathogenic variants were identified in the cohort and were grouped in two ways. First, we sorted variants in PSEN1, PSEN2, or APP by the affected protein domain. Second, we divided PSEN1 variants according to position before or after codon 200. We examined variant-dependent variability in Aß biomarkers, specifically Pittsburgh-Compound-B PET (PiB-PET) signal, levels of CSF Aß1-42 (Aß42), and levels of Aß1-40 (Aß40). FINDINGS: Cortical and striatal PiB-PET signal showed striking variant-dependent variability using both grouping approaches (p<0·0001), despite similar progression on the clinical dementia rating (p>0·7), and CSF Aß42 levels (codon-based grouping: p=0·49; domain-based grouping: p=0·095). Longitudinal PiB-PET signal also varied across codon-based groups, mirroring cross-sectional analyses. INTERPRETATION: Autosomal dominant Alzheimer's disease pathogenic variants showed highly differential temporal and regional patterns of PiB-PET signal, despite similar functional progression. These findings suggest that although increased PiB-PET signal is generally seen in autosomal dominant Alzheimer's disease, higher levels of PiB-PET signal at an individual level might not reflect more severe or more advanced disease. Our results have high relevance for ongoing clinical trials in autosomal dominant Alzheimer's disease, including those using Aß PET as a surrogate marker of disease progression. Additionally, and pertinent to both sporadic and autosomal dominant Alzheimer's disease, our results suggest that CSF and PET measures of Aß levels are not interchangeable and might reflect different Aß-driven pathobiological processes. FUNDING: National Institute on Aging, Doris Duke Charitable Foundation, German Center for Neurodegenerative Diseases, Japanese Agency for Medical Research and Development.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Adolescente , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Biomarcadores , Estudios Transversales , Heterocigoto , Humanos , Tomografía de Emisión de Positrones
13.
Alzheimers Dement ; 18(4): 645-653, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34160128

RESUMEN

INTRODUCTION: Immune dysregulation is implicated in neurodegeneration and altered cytokine levels are seen in people with dementia. However, whether cytokine levels are predictive of cognitive decline in cognitively unimpaired (CU) elderly, especially in the setting of elevated amyloid beta (Aß), remains unclear. METHODS: We measured nine cytokines in the baseline plasma of 298 longitudinally followed CU elderly and assessed whether these measures were associated with cognitive decline, alone or synergistically with Aß. We next examined associations between cytokine levels and neuroimaging biomarkers of Aß/tau/neurodegeneration. RESULTS: Higher IL-12p70 was associated with slower cognitive decline in the setting of higher Aß (false discovery rate [FDR] = 0.0023), whereas higher IFN-γ was associated with slower cognitive decline independent of Aß (FDR = 0.013). Higher IL-12p70 was associated with less tau and neurodegeneration in participants with higher Aß. DISCUSSION: Immune dysregulation is implicated in early-stage cognitive decline, and greater IL-12/IFN-γ axis activation may be protective against cognitive decline and early-stage AD progression.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Anciano , Péptidos beta-Amiloides , Biomarcadores , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Humanos , Interleucina-12 , Tomografía de Emisión de Positrones , Proteínas tau
14.
Pediatr Emerg Care ; 37(12): e821-e824, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-30973496

RESUMEN

OBJECTIVE: Screening blood work after minor injuries is common in pediatric trauma. The risk of missed injuries versus diagnostic necessity in an asymptomatic patient remains an ongoing debate. We evaluated the clinical utility of screening blood work in carefully selected asymptomatic children after minor trauma. METHODS: Patients seen at a level 1 pediatric center with "minor trauma" for blunt trauma between 2010 and 2015 were retrospectively reviewed. Exclusion criteria were age <4 of >18 years, a Glasgow Coma Scale score of <15, penetrating trauma, nonaccidental trauma, hemodynamic instability, abdominal findings (pain, distension, bruising, tenderness), hematuria, pelvic/femur fracture, multiple fractures, and operative intervention. Data abstraction included demographics, blood work, interventions, and disposition. RESULT: A total of 1308 patients were treated during the study period. Four hundred thirty-three (33%) met inclusion criteria. Mean ± SD age was 12.7 ± 4 years (range, 4-18 years), and 59% were male. Seventy-eight percent were discharged home from the emergency department. All patients had blood work. Twenty-eight percent had at least one abnormal laboratory value. The most common abnormal blood work was leukocytosis (16%). Thirty percent had an intervention, and none prompted by abnormal blood work. One patient had an intra-abdominal finding (psoas hematoma). CONCLUSION: When appropriately selected, screening laboratory testing in asymptomatic minor pediatric blunt trauma patients leads to unnecessary needle sticks without significant advantage.


Asunto(s)
Traumatismos Abdominales , Lesiones por Pinchazo de Aguja , Heridas no Penetrantes , Traumatismos Abdominales/diagnóstico , Adolescente , Niño , Preescolar , Humanos , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/diagnóstico
15.
J Laparoendosc Adv Surg Tech A ; 29(10): 1259-1263, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31553264

RESUMEN

Introduction: Although rare, major complications after gastrostomy tube placement are a significant source of morbidity in children. The purpose of this study was to identify predictors of major complications in pediatric patients undergoing gastrostomy placement. Materials and Methods: Retrospective review of surgically placed gastrostomy tubes from 2010 to 2017 was performed. Data collected included demographics, outcomes, and major complications. We divided the patients into no complications (Group 1) and major complications (Group 2). Excluded were minor complications and percutaneous endoscopic gastrostomy procedures. Results: Of 123 patients, 51.5% were males and 52% infants. Group 1 had 112 patients (91%), whereas Group 2 had 11 patients (9%). Of Group 2 patients, 3 required prolonged nil per os/total parenteral nutrition and 8 surgical reinterventions. Laparoscopy in 110 patients (89%), open surgery in 10 patients (8%), and 3 conversions to open. There were no significant differences in demographics or preoperative characteristics (albumin and comorbidities). We identified surgical approach (open: 6.3% versus 27.3%, P = .014), operative time (58 versus 85 minutes, P = .04), and use of preoperative antibiotics (63% versus 92%, P = .004) as predictors of outcomes. However, on multivariate analysis lack of preoperative antibiotics (adjusted odds ratio [aOR], 14.82 [confidence interval: 2.60-84.34], P = .002), and open procedure (aOR, 6.14 [1.01-37.24], P = .049) were independent predictors of major complications. Conclusion: Most patients with major complications after gastrostomy tube placement require surgical reintervention. Lack of preoperative antibiotics and open procedures are independent predictive factors for major complication in patients undergoing gastrostomy tube placement.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Gastrostomía , Intubación Gastrointestinal , Atención Perioperativa/métodos , Complicaciones Posoperatorias/etiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Intubación Gastrointestinal/métodos , Laparoscopía , Masculino , Oportunidad Relativa , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Factores de Riesgo
16.
Perit Dial Int ; 39(5): 405-408, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31501290

RESUMEN

Neonates requiring peritoneal dialysis (PD) catheters have been shown to have complication rates up to 70%. The presence of a concurrent stoma significantly increases the risk of peritonitis, exit-site infection, and catheter failure. As such, multiple techniques have been proposed to reduce these risks, including a chest wall exit site. In this case, the patient was born with bilateral hypoplastic kidneys and an anorectal malformation, requiring a colostomy soon after birth. At 4 weeks of life, he required placement of a PD catheter for dialysis. Given the high risk of infection, a laparoscopic-assisted PD catheter placement with a chest wall exit remote from the colostomy was performed. This report describes the operative technique including omentectomy, placement of a percutaneous stitch between the catheter cuffs, and fibrin glue injection around the catheter. The patient had no catheter-related infections. Laparoscopic-assisted PD catheter placement with chest wall exit site is a safe alternative in patients with any type of abdominal stoma.


Asunto(s)
Cateterismo/métodos , Catéteres de Permanencia , Colostomía , Laparoscopía , Diálisis Peritoneal , Estomas Quirúrgicos , Pared Torácica/cirugía , Humanos , Recién Nacido , Masculino
17.
Int J Surg Case Rep ; 60: 8-12, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31185455

RESUMEN

INTRODUCTION: Posttransplant lymphoproliferative disease (PTLD) is a known complication in patients with solid organ transplant. It can present as localized or disseminated tumor. The cornerstone of management consists of reduced immunosuppression (RI). In select cases, localized disease can potentially be curative with surgical excision. PRESENTATION OF CASE: Here we present a case of a 19-year-old female with orthotopic heart transplant with two episodes of recurrent PTLD. After the second episode she was found to have asymptomatic splenic lesions which were refractory to RI and chemotherapy. She subsequently underwent splenectomy that showed sterile necrotizing and non-necrotizing granulomas with no evidence of PTLD. DISCUSSION: Based on our literature search this is the first ever reported case of sterile granulomas in a patient with recurrent PTLD which could potentially be diagnosed with minimally invasive biopsy rather than diagnostic splenectomy. CONCLUSION: This report is an attempt to create awareness regarding potential for presence of sterile granulomas in patients with recurrent PTLD and discuss the use of percutaneous biopsy before splenectomy.

18.
Pediatr Neonatol ; 60(5): 530-536, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30737113

RESUMEN

BACKGROUND: To compare outcomes for complicated appendicitis treated with early versus interval appendectomy and to identify which patients would likely benefit from early appendectomy. METHODS: A retrospective review of complicated appendicitis was performed from 2010 to 2015. Patients were divided into early (EA) versus interval appendectomy (IA) groups. We compared demographics, complications and outcomes. Pearson's Chi square analysis and Student's T test analysis were performed. RESULTS: We identified 316 patients (EA group 53% vs. IA group 47%). Interval appendectomy group had longer symptom duration [IA 3.8 vs. EA 2.3 days (p = 0.0001)], increased leukocytosis [IA 18.7 vs. EA 17.2 (p = 0.008)], more initial abscesses [IA 35% vs. EA 13% (p = 0.0001)], more complications [IA 30% vs. EA 19%, (p = 0.013) and prolonged total length of stay [(LOS), p = 0.009]. Subgroup analysis of all patients revealed 80% of patients presented with ≤3 cm abscess and duration of symptoms (DOS) ≤5 days. Interval appendectomy patients with DOS ≤5 days and or ≤3 cm abscess on admission had no differences in clinical presentation. However, these patients had prolonged total LOS (IA 7.7 vs. EA 6.3 days, p = 0.01) and increased complications (IA 29% vs. EA 19%, p = 0.04). CONCLUSION: The majority of patients with complicated appendicitis in children present with small abscess (≤3 cm) and short symptom duration (≤5 days). This subset of patients might benefit from early appendectomy due to decreased LOS, resource utilization and reduced complications.


Asunto(s)
Absceso/cirugía , Apendicectomía , Apendicitis/complicaciones , Absceso/diagnóstico por imagen , Absceso/patología , Algoritmos , Apendicitis/cirugía , Niño , Humanos , Tiempo de Internación , Estudios Retrospectivos , Factores de Tiempo
19.
J Laparoendosc Adv Surg Tech A ; 29(2): 248-255, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30351216

RESUMEN

INTRODUCTION: Peptic ulcer disease (PUD) is a rare condition in children. Perforated peptic ulcer (PPU), a complication of PUD has an estimated mortality between 1.3% and 20%. We evaluate incidence and outcomes of PPU in children using an administrative database, perform a review of the literature, and report our technique for laparoscopic omental patch repair for PPU in two pediatric patients. MATERIALS AND METHODS: Kids' inpatient database (KID's) was analyzed for demographics, incidence, and outcomes. Incidence for each year was calculated based on the reported pediatric population in the United States for 2000, 2003, 2006, 2009, and 2012 by the U.S. Census Bureau. Additionally, we present two PPU cases, accompanied by a comprehensive review of the literature. RESULTS: The annual number of primary discharge diagnosis of PPU in the KID was 178 cases for 2000, 252 for 2003, 255 for 2006, 299 for 2009, and 266 for 2012. An increase trend over time was noted between 2000 and 2009; however, it was not statistically significant (0.05). PPU appears to be more common in Caucasian teenage boys. The mean length of stay was 8.02 days and with a statistically significant increase in healthcare charges ($33,187 versus $78,142, P = .002) when comparing year 2000-2012. DISCUSSION: PPU is a rare cause of abdominal pain in children, but still a PUD complication that requires surgery. PPU should be included in the differential diagnosis in patients presenting with acute abdominal pain of uncertain etiology and pneumoperitoneum. Laparoscopy is both diagnostic and therapeutic. Laparoscopic omental patch repair is a safe and effective treatment for PPUs.


Asunto(s)
Epiplón/trasplante , Úlcera Péptica Perforada/epidemiología , Úlcera Péptica Perforada/cirugía , Adolescente , Niño , Preescolar , Bases de Datos Factuales , Femenino , Precios de Hospital , Humanos , Incidencia , Lactante , Recién Nacido , Laparoscopía , Tiempo de Internación , Masculino , Úlcera Péptica Perforada/economía , Úlcera Péptica Perforada/etnología , Factores Sexuales , Resultado del Tratamiento , Estados Unidos/epidemiología
20.
Surg Infect (Larchmt) ; 20(3): 197-201, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30526419

RESUMEN

BACKGROUND: No consensus exists regarding duration of antibiotic therapy for complicated appendicitis treated with interval appendectomy. We hypothesized that more than two weeks of antibiotic therapy does not decrease complication rates in asymptomatic patients. PATIENTS AND METHODS: A retrospective review of all patients with complicated appendicitis treated with interval appendectomy from 2010-2015 was performed. We divided the patients in two groups (group 1, ≤2 weeks of antibiotics; group 2: >2 weeks of antibiotics). Demographics, antibiotic agents, and complications were collected. Pearson χ analysis and Student t-test analysis was performed with significance of p < 0.05. RESULTS: Total of 158 patients met inclusion criteria (group 1 [47.4%] vs. group 2 [52.5%]). Mean length of stay was 7.5 days. Abscess on admission was 26% (n = 41). The groups were demographically similar. Total complication rate was 39.2% (abscess development, n = 19; re-admissions, n = 16; interval appendectomy <28 days, n = 13; unplanned emergency department visits, n = 7; fistula, n = 4, wound infection/dehiscence, n = 3; and conversion to open surgery, n = 4). All fistulas and conversions occurred in the less than two-week group. Mean course of antibiotics was 4.1 weeks. There was no significant difference in the complication rates based on duration or type of antibiotics (p = 1.0). CONCLUSION: Treatment with more than two weeks of antibiotic therapy for complicated appendicitis does not confer any clinical benefit prior to interval appendectomy. Complications were not reduced by a prolonged course of antibiotic therapy.


Asunto(s)
Antibacterianos/administración & dosificación , Apendicectomía/métodos , Apendicitis/tratamiento farmacológico , Apendicitis/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Adolescente , Apendicitis/complicaciones , Niño , Preescolar , Quimioterapia/métodos , Femenino , Humanos , Incidencia , Masculino , Factores de Tiempo , Resultado del Tratamiento
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