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1.
Eur Spine J ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955866

RESUMEN

STUDY DESIGN: This study was a retrospective multi-center comparative cohort study. MATERIALS AND METHODS: A retrospective institutional database of operative adult spinal deformity patients was utilized. All fusions > 5 vertebral levels and including the sacrum/pelvis were eligible for inclusion. Revisions, 3 column osteotomies, and patients with < 2-year clinical follow-up were excluded. Patients were separated into 3 groups based on surgical approach: 1) posterior spinal fusion without interbody (PSF), 2) PSF with interbody (PSF-IB), and 3) anteroposterior (AP) fusion (anterior lumbar interbody fusion or lateral lumbar interbody fusion with posterior screw fixation). Intraoperative, radiographic, and clinical outcomes, as well as complications, were compared between groups with ANOVA and χ2 tests. RESULTS: One-hundred and thirty-eight patients were included for study (PSF, n = 37; PSF-IB, n = 44; AP, n = 57). Intraoperatively, estimated blood loss was similar between groups (p = 0.171). However, the AP group had longer operative times (547.5 min) compared to PSF (385.1) and PSF-IB (370.7) (p < 0.001). Additionally, fusion length was shorter in PSF-IB (11.4) compared to AP (13.6) and PSF (12.9) (p = 0.004). There were no differences between the groups in terms of change in alignment from preoperative to 2 years postoperative. There were no differences in clinical outcomes. While postoperative complications were largely similar between groups, operative complications were higher in the AP group (31.6%) compared to the PSF (5.4%) and PSF-IB (9.1) groups (p < 0.001). CONCLUSION: While there were differences in intraoperative outcomes (operative time and fusion length), there were no differences in postoperative clinical or radiographic outcomes. AP fusion was associated with a higher rate of operative complications.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38957102

RESUMEN

Sleep is a prominent physiological state observed across the animal kingdom. Yet, for some animals, our ability to identify sleep can be masked by behaviors otherwise associated with being awake, such as for some sharks that must swim continuously to push oxygenated seawater over their gills to breathe. We know that sleep in buccal pumping sharks with clear rest/activity cycles, such as draughtsboard sharks (Cephaloscyllium isabellum, Bonnaterre, 1788), manifests as a behavioral shutdown, postural relaxation, reduced responsiveness, and a lowered metabolic rate. However, these features of sleep do not lend themselves well to animals that swim nonstop. In addition to video and accelerometry recordings, we tried to explore the electrophysiological correlates of sleep in draughtsboard sharks using electroencephalography (EEG), electromyography, and electrooculography, while monitoring brain temperature. The seven channels of EEG activity had a surprising level of (apparent) instability when animals were swimming, but also when sleeping. The amount of stable EEG signals was too low for replication within- and across individuals. Eye movements were not measurable, owing to instability of the reference electrode. Based on an established behavioral characterization of sleep in draughtsboard sharks, we offer the original finding that muscle tone was strongest during active wakefulness, lower in quietly awake sharks, and lowest in sleeping sharks. We also offer several critical suggestions on how to improve techniques for characterizing sleep electrophysiology in future studies on elasmobranchs, particularly for those that swim continuously. Ultimately, these approaches will provide important insights into the evolutionary confluence of behaviors typically associated with wakefulness and sleep.

4.
J Gen Virol ; 105(7)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38980150

RESUMEN

Between 2013 and 2017, the A/Anhui/1/13-lineage (H7N9) low-pathogenicity avian influenza virus (LPAIV) was epizootic in chickens in China, causing mild disease, with 616 fatal human cases. Despite poultry vaccination, H7N9 has not been eradicated. Previously, we demonstrated increased pathogenesis in turkeys infected with H7N9, correlating with the emergence of the L217Q (L226Q H3 numbering) polymorphism in the haemagglutinin (HA) protein. A Q217-containing virus also arose and is now dominant in China following vaccination. We compared infection and transmission of this Q217-containing 'turkey-adapted' (ty-ad) isolate alongside the H7N9 (L217) wild-type (wt) virus in different poultry species and investigated the zoonotic potential in the ferret model. Both wt and ty-ad viruses demonstrated similar shedding and transmission in turkeys and chickens. However, the ty-ad virus was significantly more pathogenic than the wt virus in turkeys but not in chickens, causing 100 and 33% mortality in turkeys respectively. Expanded tissue tropism was seen for the ty-ad virus in turkeys but not in chickens, yet the viral cell receptor distribution was broadly similar in the visceral organs of both species. The ty-ad virus required exogenous trypsin for in vitro replication yet had increased replication in primary avian cells. Replication was comparable in mammalian cells, and the ty-ad virus replicated successfully in ferrets. The L217Q polymorphism also affected antigenicity. Therefore, H7N9 infection in turkeys can generate novel variants with increased risk through altered pathogenicity and potential HA antigenic escape. These findings emphasize the requirement for enhanced surveillance and understanding of A/Anhui/1/13-lineage viruses and their risk to different species.


Asunto(s)
Pollos , Hurones , Subtipo H7N9 del Virus de la Influenza A , Gripe Aviar , Pavos , Animales , Pavos/virología , Gripe Aviar/virología , Gripe Aviar/transmisión , Subtipo H7N9 del Virus de la Influenza A/genética , Subtipo H7N9 del Virus de la Influenza A/patogenicidad , Pollos/virología , Virulencia , China/epidemiología , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/transmisión , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Esparcimiento de Virus , Replicación Viral , Zoonosis/virología , Gripe Humana/virología , Gripe Humana/transmisión
5.
Sci Adv ; 10(27): eadj7402, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38959321

RESUMEN

The study of the tumor microbiome has been garnering increased attention. We developed a computational pipeline (CSI-Microbes) for identifying microbial reads from single-cell RNA sequencing (scRNA-seq) data and for analyzing differential abundance of taxa. Using a series of controlled experiments and analyses, we performed the first systematic evaluation of the efficacy of recovering microbial unique molecular identifiers by multiple scRNA-seq technologies, which identified the newer 10x chemistries (3' v3 and 5') as the best suited approach. We analyzed patient esophageal and colorectal carcinomas and found that reads from distinct genera tend to co-occur in the same host cells, testifying to possible intracellular polymicrobial interactions. Microbial reads are disproportionately abundant within myeloid cells that up-regulate proinflammatory cytokines like IL1Β and CXCL8, while infected tumor cells up-regulate antigen processing and presentation pathways. These results show that myeloid cells with bacteria engulfed are a major source of bacterial RNA within the tumor microenvironment (TME) and may inflame the TME and influence immunotherapy response.


Asunto(s)
Bacterias , RNA-Seq , Análisis de la Célula Individual , Humanos , Análisis de la Célula Individual/métodos , RNA-Seq/métodos , Bacterias/genética , Microambiente Tumoral , Células Mieloides/metabolismo , Células Mieloides/microbiología , Análisis de Secuencia de ARN/métodos , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/genética , Biología Computacional/métodos , ARN Bacteriano/genética , Neoplasias Esofágicas/microbiología , Neoplasias Esofágicas/genética , Microbiota , Análisis de Expresión Génica de una Sola Célula
6.
Artículo en Inglés | MEDLINE | ID: mdl-39016387

RESUMEN

STUDY DESIGN: Cohort study. OBJECTIVE: Validate the Surgical Apgar Score (SAS) as a means of predicting perioperative major complications occurring within 30 days after scoliosis surgery in pediatric patients with cerebral palsy (CP). SUMMARY OF BACKGROUND DATA: A patient's SAS, which is composed of three commonly recorded intraoperative variables, predicts postoperative complications after various types of spine surgery. This has not; however, been studied in pediatric patients with scoliosis and CP, a population that experiences a high incidence of complications after corrective spinal surgery. METHODS: Pediatric CP patients who underwent spinal correction surgery were included in this study. Patient background, surgical variables, and perioperative complications occurring within 30 days after surgery were collected. Patients were divided into 4 groups based on their SAS: SAS 0-4, SAS 5-6, SAS 7-8, SAS 9-10. The incidences of perioperative complications for each group were compared using a receiver operating characteristic analysis. Area under curve (AUC) is reported. RESULTS: A total of 111 patients met the inclusion criteria. There were no death cases. There were 44 (39.6%) perioperative major complications in 37 (33.3%) patients that occurred within 30 days after spine surgery. The most frequent perioperative complications were pulmonary issues (13.5%). The incidence of perioperative major complication in each SAS group was as follows: SAS 0-4; 51.6%, SAS 5-6; 30.2%, SAS 7-8; 18.5%, SAS 9-10; 0/0. When the SAS 7-8 group was set as the reference, there was no significant difference compared to SAS 5-6 (P=0.34), while the incidence rate was significantly increased in SAS 0-4 (P=0.02). The AUC was 0.65 (95% Confidence Interval: 0.54-0.75). CONCLUSIONS: Overall, there were 37 (33.3%) patients with CP who had a major complication within 30 days after spinal surgery. Lower SAS, with the 0-4 group being the cutoff, were associated with significantly higher complication rates than higher SAS groups.

7.
Glob Health Promot ; : 17579759241248624, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38822628

RESUMEN

AIM: Epidemiological research on resistance and resilience can build on models of health developed in health promotion. Nevertheless, these models need to be adjusted to approaches currently employed in epidemiology; namely, included concepts should be easy to operationalize, and links between them should be simple enough to enable statistical modeling. In addition, these models should include both individual and environmental assets. The objective of this study is to consolidate the current knowledge on health assets, adjust them to epidemiological research needs, and propose a new model of health assets for epidemiological studies on health. DESIGN: The conceptual paper was conducted according to the guidelines for the model development. METHODS: The development of the new model was made from the perspective of salutogenesis - the branch of health promotion studying the origins of health. The analysis of literature on health promotion, public health, and positive psychology was conducted to find the links connecting individual and environmental assets. RESULTS: The newly developed Dynamic Model of Health Assets circularly links individual characteristics, actions, environments, and support. Each preceding component of the model contributes to the following one; each component also independently contributes to resistance and resilience. The new model may guide large-scale epidemiological research on resistance and resilience. The model's components are easy to operationalize; the model allows for constructing multilevel models and accounting for the dynamic nature of the relationships between components. It is also generic enough to be adjusted to studying contributors to resistance and resilience to different specific diseases. CONCLUSION: The new model can guide epidemiological studies on resistance and resilience.

8.
Neurosurgery ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847527

RESUMEN

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is a leading cause of disability in the United States. Limited research exists on the influence of area-level socioeconomic status and outcomes after TBI. This study investigated the correlation between the Area Deprivation Index (ADI) and (1) 90-day hospital readmission rates, (2) facility discharge, and (3) prolonged (≥5 days) hospital length of stay (LOS). METHODS: Single-center retrospective review of adult (18 years or older) patients who were admitted for TBI during 2018 was performed. Patients were excluded if they were admitted for management of a chronic or subacute hematoma. We extracted relevant clinical and demographic data including sex, comorbidities, age, body mass index, smoking status, TBI mechanism, and national ADI. We categorized national ADI rankings into quartiles for analysis. Univariate, multivariate, and area under the receiver operating characteristic curve (AUROC) analyses were performed to assess the relationship between ADI and 90-day readmission, hospital LOS, and discharge disposition. RESULTS: A total of 523 patients were included in final analysis. Patients from neighborhoods in the fourth ADI quartile were more likely to be Black (P = .007), have a body mass index ≥30 kg/m2 (P = .03), have a Charlson Comorbidity Index ≥5 (P = .004), and have sustained a penetrating TBI (P = .01). After controlling for confounders in multivariate analyses, being from a neighborhood in the fourth ADI quartile was independently predictive of 90-day hospital readmission (odds ratio [OR]: 1.35 [1.12-1.91], P = .011) (model AUROC: 0.82), discharge to a facility (OR: 1.46 [1.09-1.78], P = .03) (model AUROC: 0.79), and prolonged hospital LOS (OR: 1.95 [1.29-2.43], P = .015) (model AUROC: 0.85). CONCLUSION: After adjusting for confounders, including comorbidities, TBI mechanism/severity, and age, higher ADI was independently predictive of longer hospital LOS, increased risk of 90-day readmission, and nonhome discharge. These results may help establish targeted interventions to identify at-risk patients after TBI.

9.
Global Spine J ; : 21925682241261662, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38832400

RESUMEN

STUDY DESIGN: Prospective multicenter database post-hoc analysis. OBJECTIVES: Opioids are frequently prescribed for painful spinal conditions to provide pain relief and to allow for functional improvement, both before and after spine surgery. Amidst a current opioid epidemic, it is important for providers to understand the impact of opioid use and its relationship with patient-reported outcomes. The purpose of this study was to evaluate pre-/postoperative opioid consumption surrounding ASD and assess patient-reported pain outcomes in older patients undergoing surgery for spinal deformity. METHODS: Patients ≥60 years of age from 12 international centers undergoing spinal fusion of at least 5 levels and a minimum 2-year follow-up were included. Patient-reported outcome scores were collected using the Numeric Rating Scale for back and leg pain (NRS-B; NRS-L) at baseline and at 2 years following surgery. Opioid use, defined based on a specific question on case report forms and question 11 from the SRS-22r questionnaire, was assessed at baseline and at 2-year follow-up. RESULT: Of the 219 patients who met inclusion criteria, 179 (81.7%) had 2-year data on opioid use. The percentages of patients reporting opioid use at baseline (n = 75, 34.2%) and 2 years after surgery (n = 55, 30.7%) were similar (P = .23). However, at last follow-up 39% of baseline opioid users (Opi) were no longer taking opioids, while 14% of initial non-users (No-Opi) reported opioid use. Regional pre- and postoperative opioid use was 5.8% and 7.7% in the Asian population, 58.3% and 53.1% in the European, and 50.5% and 40.2% in North American patients, respectively. Baseline opioid users reported more preoperative back pain than the No-Opi group (7.0 vs 5.7, P = .001), while NRS-Leg pain scores were comparable (4.8 vs 4, P = .159). Similarly, at last follow-up, patients in the Opi group had greater NRS-B scores than Non-Opi patients (3.2 vs 2.3, P = .012), but no differences in NRS-Leg pain scores (2.2 vs 2.4, P = .632) were observed. CONCLUSIONS: In this study, almost one-third of surgical ASD patients were consuming opioids both pre- and postoperatively world-wide. There were marked international variations, with patients from Asia having a much lower usage rate, suggesting a cultural influence. Despite both opioid users and nonusers benefitting from surgery, preoperative opioid use was strongly associated with significantly more back pain at baseline that persisted at 2-year follow up, as well as persistent postoperative opioid needs.

10.
J Stroke ; 26(2): 252-259, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38836272

RESUMEN

BACKGROUND AND PURPOSE: Infarct volume and other imaging markers are increasingly used as surrogate measures for clinical outcome in acute ischemic stroke research, but how improvements in these imaging surrogates translate into better clinical outcomes is currently unclear. We investigated how changes in infarct volume at 24 hours alter the probability of achieving good clinical outcome (modified Rankin Scale [mRS] 0-2). METHODS: Data are from endovascular thrombectomy patients from the randomized controlled ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial. Infarct volume at 24 hours was manually segmented on non-contrast computed tomography or diffusion-weighted magnetic resonance imaging. Probabilities of achieving good outcome based on infarct volume were obtained from a multivariable logistic regression model. The probability of good outcome was plotted against infarct volume using linear spline regression. RESULTS: A total of 1,099 patients were included in the analysis (median final infarct volume 24.9 mL [interquartile range: 6.6-92.2]). The relationship between total infarct volume and good outcome probability was nearly linear for infarct volumes between 0 mL and 250 mL. In this range, a 10% increase in the probability of achieving mRS 0-2 required a decrease in infarct volume of approximately 34.0 mL (95% confidence interval: -32.5 to -35.6). At infarct volumes above 250 mL, the probability of achieving mRS 0-2 probability was near zero. The relationships of tissue-specific infarct volumes and parenchymal hemorrhage volume generally showed similar patterns, although variability was high. CONCLUSION: There seems to be a near-linear association between total infarct volume and probability of achieving good outcome for infarcts up to 250 mL, whereas patients with infarct volumes greater than 250 mL are highly unlikely to have a favorable outcome.

11.
Br J Sociol ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38878298

RESUMEN

What are the historical conditions under which a sociologically informed understanding of health inequality can emerge in the public sphere? We seek to address this question through the lens of a strategically chosen historical puzzle-the stubborn persistence of and salient variation in high infant mortality rates across British industrial towns at the dawn of the previous century-as analysed by Arthur Newsholme, the Medical Officer of the Local Government Board. In doing so, we retrace the historical processes through which the evolving public health movement gradually helped crystallise a scientific understanding of the social causes of excess mortality. We map the dominant ideology of the public sphere at the time, chart the shifting roles of the state, and retrace the historical origins and emergence of 'public health' as a distinctive category of state policy and public discourse. We situate the public health movement in this historical configuration and identify the cracks in the existing ideological and administrative edifice through which this movement was able to articulate a novel approach to population health-one that spotlights the political economy of social inequality. We relate this historical sequence to the rise of industrial capitalism, the social fractures that it spawned, and the organised counter-movements that it necessitated.

12.
JAMA Netw Open ; 7(6): e2415643, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38904964

RESUMEN

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.


Asunto(s)
Vértebras Cervicales , Riluzol , Humanos , Riluzol/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Método Doble Ciego , Vértebras Cervicales/cirugía , Anciano , Enfermedades de la Médula Espinal/cirugía , Enfermedades de la Médula Espinal/tratamiento farmacológico , Espondilosis/cirugía , Espondilosis/tratamiento farmacológico , Resultado del Tratamiento , Fármacos Neuroprotectores/uso terapéutico
13.
Circ Res ; 135(2): e4-e23, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38860377

RESUMEN

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.


Asunto(s)
Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Macrófagos , Placa Aterosclerótica , Receptores de Superficie Celular , Humanos , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos de Diferenciación Mielomonocítica/genética , Animales , Antígenos CD/metabolismo , Antígenos CD/genética , Macrófagos/metabolismo , Macrófagos/patología , Placa Aterosclerótica/patología , Placa Aterosclerótica/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética , Ratones , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/patología , Masculino , Ratones Noqueados para ApoE , Ratones Endogámicos C57BL , Apoptosis , Femenino , Transición Epitelial-Mesenquimal , Vasos Coronarios/patología , Vasos Coronarios/metabolismo
14.
JCI Insight ; 9(12)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38912579

RESUMEN

Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded, as there was no cross-reactivity between SIV and SHIV envelope antibodies. After 8 low-dose intrarectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated efficacy, compared with 6 naive controls, suggesting protection was achieved in the absence of anti-envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity, identified mechanisms, and may provide opportunities for novel HIV vaccines or therapeutic strategy development.


Asunto(s)
Linfocitos T CD8-positivos , Inmunidad Innata , Macaca mulatta , Vacunas contra el SIDAS , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunología , Vacunas contra el SIDAS/inmunología , Inmunidad Innata/inmunología , Linfocitos T CD8-positivos/inmunología , Anticuerpos Antivirales/inmunología , Masculino , Vacunas Atenuadas/inmunología
15.
Global Spine J ; : 21925682241264768, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904146

RESUMEN

STUDY DESIGN: Retrospective. OBJECTIVE: Severe curves >100° in adolescent idiopathic scoliosis (AIS) are rare and require careful operative planning. The aim of this study was to assess baseline, perioperative, and 2-year differences between anterior release with posterior instrumentation (AP), posterior instrumentation with posterior column osteotomies (P), and posterior instrumentation with 3-column vertebral osteotomies (VCR). METHODS: Two scoliosis datasets were queried for primary cases of severe thoracic AIS (≥100°) with 2-year follow-up. Pre- and 2-year postoperative radiographic measures (2D and estimated 3D kyphosis), clinical measurements, and SRS-22 outcomes were compared between three approaches. RESULTS: Sixty-one patients were included: 16 AP (26%), 38 P (62%), 7 VCR (11%). Average age was 14.4 ± 2.0 years; 75.4% were female. Preoperative thoracic curve magnitude (AP: 112°, P: 115°, VCR: 126°, P = 0.09) and T5-T12 kyphosis (AP: 38°, P: 59°, VCR: 70°, P = 0.057) were similar between groups. Estimated 3D kyphosis was less in AP vs P (-12° vs 4°, P = 0.016). Main thoracic curves corrected to 36° in AP vs 49° and 48° for P and VCR, respectively (P = 0.02). Change in estimated 3D kyphosis was greater in AP vs P and VCR (34° vs 13°, P = 0.009; 34° vs 7°, P = 0.046). One incomplete spinal cord injury had residual deficits (P; 1/61, 1.6%). All SRS-22 domains improved postoperatively. CONCLUSION: All approaches obtained satisfactory coronal and sagittal correction, but AP had smaller residual coronal deformity and greater kyphosis restoration than the other approaches. This information may help inform the decision of whether to include an anterior release for large thoracic AIS curves.

16.
Spine Deform ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696080

RESUMEN

PURPOSE: To review the current literature surrounding the assessment of self-image in pediatric and adult spinal deformity. METHODS: The literature were reviewed for studies examining patient-reported outcome measurements (PROM) and self-image in pediatric and adult spinal deformity. PROM performance metrics were collected and described. The relationships between self-image PROM and patient outcomes, including satisfaction, were described. RESULTS: Several self-image PROM exist, including the Scoliosis Research Society-22r (SRS-22r) self-image domain, the Body Image Disturbance Questionnaire (BIDQ), and the Spinal Appearance Questionnaire (SAQ). The most commonly used is the self-image domain of the SRS-22r. It is validated in adult and pediatric spinal deformity and is correlated with patient desire for surgery and satisfaction after surgery. This domain is limited by floor and ceiling effects. CONCLUSION: Self-image assessment is critical to both pediatric and adult spinal deformity surgeries. The SRS-22r self-image domain is the most frequently reported PROM for this health domain. While valid in both surgical cohorts, this PROM is affected by floor and ceiling effects which limits the ability to discriminate between health states. Given the overall importance of this domain to patients with spinal deformity further efforts are needed to improve discrimination without gross increases in PROM question burden, which may limit broad acceptance and use.

17.
Abdom Radiol (NY) ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744703

RESUMEN

Ovarian cancer is associated with high cancer-related mortality rate attributed to late-stage diagnosis, limited treatment options, and frequent disease recurrence. As a result, careful patient selection is important especially in setting of radical surgery. Radiomics is an emerging field in medical imaging, which may help provide vital prognostic evaluation and help patient selection for radical treatment strategies. This systematic review aims to assess the role of radiomics as a predictor of disease recurrence in ovarian cancer. A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Studies meeting inclusion criteria investigating the use of radiomics to predict post-operative recurrence in ovarian cancer were included in our qualitative analysis. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools. Six retrospective studies met the inclusion criteria, involving a total of 952 participants. Radiomic-based signatures demonstrated consistent performance in predicting disease recurrence, as evidenced by satisfactory area under the receiver operating characteristic curve values (AUC range 0.77-0.89). Radiomic-based signatures appear to good prognosticators of disease recurrence in ovarian cancer as estimated by AUC. The reviewed studies consistently reported the potential of radiomic features to enhance risk stratification and personalise treatment decisions in this complex cohort of patients. Further research is warranted to address limitations related to feature reliability, workflow heterogeneity, and the need for prospective validation studies.

18.
Int J Colorectal Dis ; 39(1): 82, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38809315

RESUMEN

INTRODUCTION: Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC. METHODS: PubMed, EMBASE and Web of Science were searched as part of our review. Studies investigating the utility of ctDNA in locally advanced rectal cancer (LARC) were assessed for eligibility. Quality assessment of included studies was performed using the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, ctDNA details and survival data. A meta-analysis was performed on eligible studies to determine pooled recurrence-free survival (RFS). RESULTS: Twenty-two studies involving 1676 participants were included in our analysis. Methodological quality categorised by the Newcastle Ottawa Scale was generally satisfactory across included studies. ctDNA detected at various time intervals was generally associated with poor outcomes across included studies. Meta-analysis demonstrated a pooled hazard ratio of 8.87 (95% CI 4.91-16.03) and 15.15 (95% CI 8.21-27.95), indicating an increased risk of recurrence with ctDNA positivity in the post-neoadjuvant and post-operative periods respectively. CONCLUSION: Our systematic review provides evidence supporting the prognostic utility of ctDNA in patients with LARC, particularly in identifying patients at higher risk of disease recurrence in the post-neoadjuvant and post-operative periods.


Asunto(s)
Biomarcadores de Tumor , ADN Tumoral Circulante , Neoplasias del Recto , Humanos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Supervivencia sin Enfermedad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/genética , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/sangre , Neoplasias del Recto/genética , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Neoplasias del Recto/diagnóstico
19.
Artículo en Inglés | MEDLINE | ID: mdl-38819199

RESUMEN

STUDY DESIGN: Retrospective Database review. OBJECTIVE: Analyze revisions of CDAs reported to the MAUDE database. SUMMARY OF BACKGROUND DATA: Cervical disc arthroplasty (CDA) has emerged as a motion-preserving alternative to anterior cervical discectomy and fusion (ACDF) for degenerative cervical disease, demonstrating comparable outcomes. Despite the availability of variable CDA designs, there is limited data on the specific complications of individual CDAs. The Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database has been used to systematically report complications associated with CDAs. However, data on specific reasons for CDA revision remains scarce. The purpose of this study is to compare common complications associated with revision for different CDAs. METHODS: The MAUDE database was queried from January 2005 to September 2023, including all nine FDA-approved CDAs. The full-text reports of each complication were categorized based on whether revision surgery was performed, the complications and the type of CDA collected and compared. RESULTS: A total of 678 revisions for nine CDAs were reported: Mobi-C (239), M6 (167), Prodisc-C (88), Prestige (60), PCM (44), Bryan (35), Secure (23), Simplify (21), and Discover (1). The top three complications associated with revision were migration (23.5%), neck pain (15.5%), and heterotopic ossification (6.6%). The most common complications per device were migration for Mobi-C (26.4%), Prodisc-C (21.3%), Prestige (24.6%), PCM (84.1%), Bryan (48.6%), Secure (30.4%), and Discover (100%). For M6, the most common complications associated with revision surgery were osteolysis (18.6%) and neck pain (18.6%), while neck pain (23.8%) was the most common for the Simplify. CONCLUSION: The MAUDE database highlights complications related to CDA revision in which the primary complications consistently include implant migration, neck pain, and heterotopic ossification ,varying in their rerelvance depending on the CDA.

20.
Anal Methods ; 16(23): 3692-3700, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38805075

RESUMEN

Polar pesticides such as anionic or ionisable compounds have always provided a challenge for analytical chemists. Methods of analysis have been developed using a range of techniques including normal phase chromatography, ion-pairing, derivatisation and HILIC or multi-mode chromatography. These work well with some of these compounds but, except for HILIC, all of them have their limitations and none of them cover the range required by legislation. Some of these compounds, glyphosate, chlorate and phosphonic acid, are found regularly in a range of food matrices, and therefore reliable methods of analysis are essential. This study describes an ion chromatography method with tandem mass spectrometry detection which not only covers the full range of compounds required by legislation but also can be expanded to include other anionic or ionisable pesticides and metabolites. These include glyphosate and its metabolites, glufosinate and its metabolites, ethephon and its metabolites as well as fosetyl aluminium, chlorate and perchlorate. The method is fully validated according to the performance criteria from the SANTE guidelines for the analysis of pesticides in food and feed over a wide range of matrices, including milk, infant formula, cereals and fruits and vegetables. Over 300 food samples have analysed as part of our routine monitoring program.


Asunto(s)
Grano Comestible , Frutas , Plaguicidas , Espectrometría de Masas en Tándem , Verduras , Espectrometría de Masas en Tándem/métodos , Grano Comestible/química , Verduras/química , Frutas/química , Plaguicidas/análisis , Leche/química , Fórmulas Infantiles/química , Animales , Contaminación de Alimentos/análisis , Humanos , Análisis de los Alimentos/métodos , Residuos de Plaguicidas/análisis , Aniones/análisis , Glicina/análogos & derivados , Glicina/análisis , Glicina/química , Cromatografía por Intercambio Iónico/métodos
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