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1.
Transl Anim Sci ; 8: txae093, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38979117

RESUMEN

This study evaluated the association between the proportion of Brahman genetics and productivity of Brahman-Angus cows at weaning using a 31-yr dataset containing 6,312 cows and 5,405 pregnancies. Cows were contemporaneously reared and enrolled in yearly breeding seasons under subtropical conditions of North-Central Florida. They were evenly distributed in six-breed groups (G) according to the proportion of Brahman genetics: G0% to 19%, G21% to 34%, G38% (Brangus), G41% to 59%, G63% to 78%, and G81% to 100%. The proportion of cows calving (84.9%) did not differ across the six-breed groups. However, cows in the G81% to 100% weaned fewer calves (90.8%) than cows in the G0% to 19% and G21% to 34% (95.7%, each). The weaning rate of cows in the G38% (94.3%), G41% to 59% (94.2%), and G63% to 78% (93.0%) was intermediate between these three breed groups. The preweaning calf mortality was greater for cows in the G81% to 100% (9.2%) than cows in the G0% to 19% and G21% to 34% (4.3%, each), but intermediate for cows in the G38% (5.7%), G41% to 59% (5.8%), and G63% to 78% (7.0%). Cows in the G81% to 100% also weaned lighter calves (220.6 kg) than cows in the G0% to 19% (245.2 kg), G21% to 34% (250.2 kg), G38% (247.9 kg), G41% to 59% (252.5 kg), and G63% to 78% (245.2 kg). Cows in the G0% to 19% weaned lighter calves than cows with 21% to 78% of Brahman genetics. The 205-d adjusted weaning weight evidenced the less productive results of cows in G0% to 19% and G81% to 100% compared with other genetic groups, as they calved at the fastest and slowest rate, respectively. Thus, the 205-d adjusted weaning weight eliminated this bias. Additionally, younger cows weaned lighter calves; and male calves were heavier at weaning than female calves. Both parity order of cow and calf sex altered the magnitude of the described association between breed group of cows and calf weaning weights. Overall, after adjusting for weaning rate and age of calves at weaning, the number of kilograms produced per cow submitted to reproduction was less for cows in the G0% to 19% (191.1 kg) and G81% to 100 (181.8 kg) compared with cows in the G21% to 34 (197.0 kg), G38 (195.9 kg), G41% to 59 (199.7), and G63% to 78 (196.2). Cows in the G81% to 100% were the least productive. Thus, a proportion of Brahman genetics between 21% and 78% ensured superior productivity of Brahman-Angus cows subjected to subtropical conditions.

2.
J Neurosurg Spine ; 39(6): 729-733, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37728381

RESUMEN

OBJECTIVE: Spinal meningiomas are one of the most common primary intradural tumors of the adult spine. Spinal meningiomas typically have a benign course with low rates of recurrence. Recent advances in genomic profiling have provided valuable information on meningioma biology and natural history, but these studies have focused primarily on cranial meningiomas. Chromosomal copy number analysis of meningiomas has been shown to be a valuable molecular profiling technique for distinguishing benign from aggressive tumors. The Integrated Grade for Meningioma is a novel grading scheme that uses mitotic index and copy-number profile to identify aggressive tumors at high risk for recurrence. The integrated grade has been shown to be a better predictor of tumor behavior than WHO grade alone. The objective of this study was to evaluate the chromosomal copy-number profile of spinal meningiomas, and to correlate these findings with the assigned WHO grades. METHODS: The authors evaluated 94 spinal meningiomas treated surgically at their institution between 2002 and 2022. The histopathological results including WHO grade, mitotic index, presence of atypical features, and MIB-1 index were recorded. Chromosomal copy number as determined by institutional whole-genome DNA copy-number profiling was available for 57 tumors. RESULTS: The WHO grades of the cohort consisted of 81 (86%) WHO grade 1 tumors and 13 (14%) WHO grade 2 tumors. In tumors for which copy-number profiling was available, 44 (77%) of 57 demonstrated loss of 22q/NF2. Notably absent were frequent high-risk copy number alterations including loss of 1p, 3p, 4p/q, 6p/q, 10p/q, 14q, 18p/q, 19p/q, and focal loss of CDKN2A on 9p. Of the 9 WHO grade 2 tumors for which copy-number profiling was available, 6 tumors were reclassified to a lower risk profile (integrated grade 1). CONCLUSIONS: This analysis suggests that spinal meningiomas exhibit overwhelmingly indolent biology, as supported by their benign integrated grade. These findings have implications in the surgical management of these patients in relation to the need for complete Simpson grade I resection, as well as the potential avoidance of adjuvant therapy following surgery in the setting of otherwise frequently benign pathology.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Adulto , Humanos , Meningioma/genética , Meningioma/cirugía , Meningioma/patología , Genómica , Terapia Combinada , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología
3.
J Anim Sci ; 100(12)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36331079

RESUMEN

Bos taurus × Bos indicus crosses are widespread in tropical and subtropical regions, nonetheless, quantitative information about the influence of B. indicus genetics on the reproductive performance of beef cattle is lacking. Herein, we determined the association between level of B. indicus genetics and reproduction from a 31-yr dataset comprising sequential breeding seasons of the University of Florida multibreed herd (n = 6,503 Angus × Brahman cows). The proportion of B. indicus genetics in this herd is evenly distributed by each 1/32nd or approximately 3-percentage points. From 1989 to 2020, the estrous cycle of cows was synchronized for artificial insemination (AI) based on detected estrus or timed-AI (TAI) using programs based on gonadotropin-releasing hormone and prostaglandin, and progestin/progesterone. All cows were exposed to natural service after AI and approximately 90-d breeding seasons, considering the day of AI as day 0. The proportion of B. indicus genetics of cows was associated negatively with pregnancy per AI, ranging from 51.6% for cows with 0%-19% of B. indicus genetics to 37.4% for cows with 81%-100% of B. indicus genetics. Similar association was found for estrous response at the end of the synchronization protocol, ranging from 66.3% to 38.4%, respectively. This reduced estrous response helped to explain the pregnancy results, once the pregnancy to AI of cows showing estrus was 2.3-fold greater than for those not showing estrus and submitted to TAI. Despite reduced pregnancy per AI, the increase in the proportion of B. indicus genetics of cows was not associated with a reduction in the proportion of pregnant cows at the end of the breeding season. Nevertheless, the interval from entering the breeding season to pregnancy was lengthened as the proportion of B. indicus genetics of cows increased. The median days to pregnancy was extended by 25 when the proportion of B. indicus genetics surpassed 78% compared with less than 20%. Thus, the increase in the proportion of B. indicus genetics of cows was related to a reduction in pregnancy per AI and lengthening the interval to attain pregnancy during the breeding season, but not with the final proportion of pregnant cows. As a result, reproductive management strategies directed specifically to cows with a greater proportion of B. indicus genetics are needed to improve the rate of pregnancy in beef herds.


Cow­calf operations in the tropics and sub-tropics have benefited from the environmental adaptation provided by Bos indicus genetics. However, reproductive performance has been a cause of concern, although poorly quantified. This study characterized how much the B. indicus genetics in crossbred cows influence herd reproduction. We analyzed data from cows with known proportions of Angus and Brahman genetics, from the same crossbred herd, for 31 sequential breeding seasons. The increase in the proportion of B. indicus genetics reduced estrous response and pregnancy per artificial insemination after estrous synchronization, but not the proportion of pregnant cows at the end of the breeding season. Interval from the beginning of the breeding season to pregnancy was extended by 25 d when the proportion of B. indicus genetics surpassed 78%. In conclusion, reproductive management strategies directed specifically to cows with a greater proportion of B. indicus genetics are needed to improve the rate of pregnancy in beef herds.


Asunto(s)
Dinoprost , Sincronización del Estro , Embarazo , Femenino , Bovinos/genética , Animales , Sincronización del Estro/métodos , Inseminación Artificial/veterinaria , Inseminación Artificial/métodos , Reproducción/genética , Estro , Progesterona , Hormona Liberadora de Gonadotropina/genética
4.
Cell ; 185(14): 2591-2608.e30, 2022 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-35803246

RESUMEN

Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant intra-tumoral B to plasma cell differentiation in lymphoid aggregates in MBM. MBM harbored larger fractions of monocyte-derived macrophages and dysfunctional TOX+CD8+ T cells with distinct expression of immune checkpoints. This work provides comprehensive insights into MBM biology and serves as a foundational resource for further discovery and therapeutic exploration.


Asunto(s)
Neoplasias Encefálicas , Melanoma , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Linfocitos T CD8-positivos/patología , Ecosistema , Humanos , RNA-Seq
5.
Dermatol Ther ; 35(8): e15609, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35634721

RESUMEN

Invasive fungal infection is a rare but serious potential consequence of biologic therapy. Herein, we report a case of cryptococcal meningitis in an otherwise immunocompetent patient receiving ixekizumab for the treatment of severe plaque psoriasis. We also discuss the relevant immunologic role of interleukin-17, the potential for synergistic effects when transitioning biologic therapies, and clinical considerations when treating patients with such medications. To the best of our knowledge, this is the first case of cryptococcal meningitis reported in a patient treated with ixekizumab.


Asunto(s)
Meningitis Criptocócica , Psoriasis , Humanos , Interleucina-17 , Meningitis Criptocócica/inducido químicamente , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
6.
BMC Infect Dis ; 22(1): 141, 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35144555

RESUMEN

BACKGROUND: Intramedullary abscesses are rare infections of the spinal cord. Intramedullary abscesses often have a complex presentation, making a high index of suspicion essential for prompt diagnosis and management. CASE PRESENTATION: We present two cases of intramedullary abscesses referred to and ultimately managed at our institution. Delayed diagnosis occurred in both instances due to the rarity of intramedullary abscesses and their propensity to mimic other pathologies. For both patients, prompt surgical management and the rapid institution of broad-spectrum antibiotics were critical in preventing further neurological decline. CONCLUSIONS: Although rare, it is critical to consider intramedullary abscesses on the differential for any MRI lesions that are hyperintense on T2 and peripherally enhancing on T1 post-contrast sequences, as even short delays in treatment can lead to severe neurological damage.


Asunto(s)
Enfermedades de la Médula Espinal , Streptococcus anginosus , Absceso/diagnóstico , Humanos , Imagen por Resonancia Magnética , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/tratamiento farmacológico
7.
Oper Neurosurg (Hagerstown) ; 22(4): 249-254, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35156942

RESUMEN

BACKGROUND: Spinal navigation technology has revolutionized the field of spine surgery. However, adoption has not been universal. Reasons include cost, interruption in surgical workflow, increased OR time, and potential implant incompatibility, among others. A technology that maintains performance but alleviates these drawbacks would be valuable. A mobile device-based navigation system has been developed which relies on the iOS platform and the gyroscopic-on-chip technology, therein to guide accurate placement of pedicle screws. This system maintains a minimal footprint and resolves difficulty with line-of-sight interruption and attention shift. OBJECTIVE: To evaluate the accuracy and reliability of this device in a preclinical setting. METHODS: A cadaver study was performed involving 13 surgeons placing 26 pedicle screws using the novel assistive technology. CT scans were then performed, and accuracy was assessed by designating each screw a Gertzbein-Robbins score. In addition, bench top table testing was performed. This consisted of 360 tests of both the accuracy of the device's pitch and roll, corresponding to the rotation about the device's x-axis and y-axis, respectively. RESULTS: The mean Gertzbein-Robbins score of the 26 screws placed in the cadaver study was 1.29. The mean deviation from centerline pedicle placement was 0.66 mm, with a standard deviation of 1.52 mm. The bench top study results included a mean pitch error of 0.17° + 0.09° and a mean roll error of 0.29 + 0.21. CONCLUSION: The novel mobile device-based navigation system for placement of pedicle screws presented here demonstrates high levels of accuracy and reliability in the preclinical setting.


Asunto(s)
Vértebras Lumbares , Tornillos Pediculares , Cadáver , Computadoras de Mano , Humanos , Vértebras Lumbares/cirugía , Reproducibilidad de los Resultados
8.
Neuro Oncol ; 24(1): 101-113, 2022 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-34015129

RESUMEN

BACKGROUND: Programmed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy. METHODS: Twenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor-infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale. RESULTS: Enrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected adverse events. Six-month progression-free survival (PFS-6) rate was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was >10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased posttreatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO. CONCLUSION: Nivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Antígeno B7-H1 , Humanos , Neoplasias Meníngeas/tratamiento farmacológico , Meningioma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nivolumab/uso terapéutico , Receptor de Muerte Celular Programada 1
9.
Neuro Oncol ; 24(5): 796-808, 2022 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-34508644

RESUMEN

BACKGROUND: Meningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management. METHODS: We evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms. RESULTS: We developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score. CONCLUSION: We propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Adulto , Estudios de Cohortes , Humanos , Neoplasias Meníngeas/patología , Meningioma/patología , Clasificación del Tumor , Recurrencia Local de Neoplasia/genética , Pronóstico , Estudios Retrospectivos , Organización Mundial de la Salud
10.
Front Microbiol ; 12: 772863, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34745079

RESUMEN

Calf diarrhea is one of the most concerning challenges facing both the dairy and beef cattle industry. Maintaining healthy gut microbiota is essential for preventing gastrointestinal disorders. Here, we observed significantly less bacterial richness in the abnormal feces with watery or hemorrhagic morphology compared to the normal solid feces. The normal solid feces showed high relative abundances of Osllospiraceae, Christensenellaceae, Barnesiella, and Lactobacillus, while the abnormal feces contained more bacterial taxa of Negativicutes, Tyzzerella, Parasutterella, Veillonella, Fusobacterium, and Campylobacter. Healthy calves had extensive bacterial-bacterial correlations, with negative correlation between Lactobacillus and potential diarrheagenic Escherichia coli-Shigella, but not in the abnormal feces. We isolated Lactobacillus species (L. reuteri, L. johnsonii, L. amylovorus, and L. animalis), with L. reuteri being the most abundant, from the healthy gut microbiota. Isolated Lactobacillus strains inhibited pathogenic strains including E. coli K88 and Salmonella Typhimurium. These findings indicate the importance of a diverse gut microbiota in newborn calf's health and provide multiple potential probiotics that suppress pathogen colonization in the gastrointestinal tract to prevent calf diarrhea.

11.
J Neurosurg Spine ; 36(3): 347-349, 2021 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-34624836
12.
Spine (Phila Pa 1976) ; 46(2): E126-E132, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32991515

RESUMEN

STUDY DESIGN: A prospective multicenter investigational device exempt trial is underway evaluating a novel conformable mesh interbody fusion device in subjects undergoing single-level fusion for degenerative disc disease. Patients meeting inclusion and exclusion criteria were offered enrollment. There is no comparative group in this study. OBJECTIVE: Establish the short and long-term safety and effectiveness of a novel conformable mesh interbody fusion device in subjects undergoing single-level fusion for degenerative disc disease unresponsive to conservative care. SUMMARY OF BACKGROUND DATA: Transforaminal lumbar interbody fusion remains a critical procedure for patients with degenerative lumbar disc disease. Increasingly minimally invasive techniques have been proposed to minimize muscle dissection and tissue damage with the goal of minimizing pain and length of stay. METHODS: One hundred two subjects were enrolled across 10 sites. Ninety nine subjects remained available for follow-up at 12-months. Physical evaluations/imaging were performed serially through 12-months. Validated assessment tools included 100 mm visual analogue scale (VAS) for pain, Oswestry Disability Index (ODI) for function, and computerized tomography scan for fusion. Independent committees were used to identify adverse events and for assessment of radiographic fusion. RESULTS: Reductions in low back pain (LBP)/leg pain and improvements in functional status occur early and are maintained through 12-month follow-up. Mean VAS-LBP change from baseline to 6-weeks post-op (-46 mm) continued to improve through 12 months (-51 mm). Similar trends were observed for leg pain. Mean ODI change from baseline to 6 weeks post-op (-17) was almost doubled by 12 months (-32). Fusion rates at 12-months are high (98%). No device-related serious adverse events have occurred. CONCLUSION: 12-month outcomes demonstrated excellent patient compliance and positive outcomes for pain, function, fusion, and device safety. Clinical improvements were observed by 6-weeks post-op and appear durable up to 1 year later. A novel mesh interbody device may provide an alternative means of interbody fusion that reduces connective tissue disruption.Level of Evidence: 3.


Asunto(s)
Fusión Vertebral/instrumentación , Mallas Quirúrgicas , Adulto , Anciano , Dolor de Espalda , Femenino , Humanos , Vértebras Lumbares/cirugía , Región Lumbosacra/cirugía , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Prótesis e Implantes , Resultado del Tratamiento , Escala Visual Analógica
13.
Int J Spine Surg ; 15(6): 1103-1114, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35086867

RESUMEN

BACKGROUND: Interbody fusion is a widely utilized and accepted procedure to treat advanced debilitating lumbar degenerative disc disease (DDD). Increasingly, surgeons are seeking interbody devices that are large for stability and grafting purposes but can be inserted with less invasive techniques. To achieve these contrary objectives a novel, conformable mesh interbody fusion device was designed to be placed in the disc space through a small portal and filled with bone graft in situ to a large size. This design can reduce the risk of trauma to surrounding structures while creating a large graft footprint that intimately contours to the patient's own anatomy. The purpose of this Investigational Device Exempt (IDE) trial was to evaluate the perioperative and long-term results of this novel conformable mesh interbody fusion device. METHODS: This investigation is a prospective, multicenter, single-arm, Food and Drug Administration and Institutional Review Board-approved IDE, performance goal trial. A total of 102 adults presenting with DDD at a single level between L2 and S1 and unresponsive to 6 months conservative care had instrumented lumbar interbody fusion. Validated assessment tools include 100 mm visual analog scale for pain, Oswestry Disability Index (ODI) for function, single question survey for patient satisfaction, and computed tomography (CT) scan for fusion. Patients were enrolled across 10 geographically distributed sites. Pain/ODI surveys, physical evaluations, and imaging were performed serially through 24 months. Specifically, CT was performed at 12 and, if not fused, 24 months. Independent radiologists assessed CTs for fusion. An independent committee adjudicated adverse events. Patients with complete data at 24 months were included in the analysis. RESULTS: Ninety-six (96, 94% follow-up rate) patients (57.0 ± 12.0 years, 50.0% female, Body Mass Index 30.6 ± 4.9) reported average decreased low back pain from baseline of 45.0 ± 26.6 at 6 weeks and 51.4 ± 26.2 at 24 months. Right/left leg pain reduced by 28.9 ± 36.7/37.8±32.4 at 6 weeks and 30.5±33.0/40.3 34.6 at 24 months. Mean ODI improved 17.1 ± 18.7 from baseline to 6 weeks and 32.0 ± 18.5 by 24 months. At 24 months, 91.7% of patients rated their procedure as excellent/good. Fusion rates were 97.9% (94/96) at 12 months, and 99% (95/96) at 24 months. Mean operative time, estimated blood loss, and length of stay were 2.6 ± 0.9 hours, 137 ± 217 mL, and 2.3 ± 1.2 days, respectively. No device-related serious adverse events have occurred. CONCLUSIONS: Clinically significant outcomes for pain, function, fusion, and device safety were demonstrated in this population. Substantial clinical improvements occur by 6 weeks postoperative and continue to improve to 24 months. The successful outcomes observed in this trial support use of this novel device in an instrumented lumbar interbody fusion. LEVEL OF EVIDENCE: 3. CLINICAL RELEVANCE: This reports substantiates that the preliminary 1-year findings published earlier for this investigation are confirmed and the fusion rates and that patient improvements reported are sustained through 2 years.

14.
Nat Commun ; 11(1): 3912, 2020 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-32764562

RESUMEN

Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. Here, we generate distinct imageable syngeneic mouse GBM-tumor models and utilize RNA-sequencing, CyTOF and correlative immunohistochemistry to assess immune-profiles in these models. We identify immunologically-inert and -active syngeneic-tumor types and show that inert tumors have an immune-suppressive phenotype with numerous exhausted CD8 T cells and resident macrophages; fewer eosinophils and SiglecF+ macrophages. To mimic the clinical-settings of first line of GBM-treatment, we show that tumor-resection invigorates an anti-tumor response via increasing T cells, activated microglia and SiglecF+ macrophages and decreasing resident macrophages. A comparative CyTOF analysis of resected-tumor samples from GBM-patients and mouse GBM-tumors show stark similarities in one of the mouse GBM-tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients.


Asunto(s)
Neoplasias Encefálicas/inmunología , Glioblastoma/inmunología , Animales , Encéfalo/inmunología , Encéfalo/patología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Línea Celular Tumoral , Glioblastoma/patología , Glioblastoma/terapia , Humanos , Tolerancia Inmunológica , Inmunofenotipificación , Inmunoterapia , Isoinjertos , Linfocitos Infiltrantes de Tumor/clasificación , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/patología , Neoplasias Experimentales/terapia , Microambiente Tumoral/inmunología
15.
Surg Pathol Clin ; 13(2): 291-303, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32389268

RESUMEN

Mesenchymal tumors of the central nervous system (CNS) comprise an array of neoplasms that may arise from or secondarily affect the CNS and its immediate surroundings. This review focuses on meningiomas and solitary fibrous tumors, the most common primary CNS mesenchymal tumors, and discusses recent advances in unveiling the molecular landscapes of these neoplasms. An effort is made to underscore those molecular findings most relevant to tumor diagnostics and prognostication from a practical perspective. As molecular techniques become more readily used at the clinical level, such alterations may strengthen formal grading schemes and lend themselves to treatment with targeted therapies.


Asunto(s)
Neoplasias del Sistema Nervioso Central/diagnóstico , Encéfalo/patología , Neoplasias del Sistema Nervioso Central/patología , Humanos , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patología , Meningioma/diagnóstico , Meningioma/patología , Pronóstico , Tumores Fibrosos Solitarios/diagnóstico , Tumores Fibrosos Solitarios/patología
16.
World Neurosurg ; 137: 292-295, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32068170

RESUMEN

BACKGROUND: Lumbar puncture is a common procedure that can be safely performed in most patients. Certain populations may have increased risk for complications following lumbar puncture, but the significance of basilar invagination is often underappreciated. CASE DESCRIPTION: A 45-year-old woman with basilar invagination received multiple lumbar punctures in the workup of acute meningitis. Preprocedural computed tomography was obtained. Following lumbar puncture, the patient developed locked-in syndrome. Magnetic resonance imaging obtained several days later demonstrated severe compression and infarction of the medulla and inferior cerebellum by the odontoid process and ectopic cerebellar tonsils. The patient was transferred but at this point, surgical decompression was not possible. She did not regain significant neurologic function. CONCLUSIONS: Basilar invagination is a risk factor for devastating neurologic complications following lumbar puncture. Awareness of this complication and prompt recognition of its occurrence may prevent future morbidity of lumbar puncture in patients with basilar invagination.


Asunto(s)
Infartos del Tronco Encefálico/diagnóstico por imagen , Síndrome de Enclaustramiento/diagnóstico , Bulbo Raquídeo/irrigación sanguínea , Bulbo Raquídeo/diagnóstico por imagen , Meningitis Neumocócica/diagnóstico , Platibasia/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico , Punción Espinal/efectos adversos , Infartos del Tronco Encefálico/etiología , Cerebelo/anomalías , Cerebelo/diagnóstico por imagen , Femenino , Humanos , Síndrome de Klippel-Feil/complicaciones , Síndrome de Klippel-Feil/cirugía , Síndrome de Enclaustramiento/diagnóstico por imagen , Síndrome de Enclaustramiento/etiología , Imagen por Resonancia Magnética , Meningitis Neumocócica/complicaciones , Persona de Mediana Edad , Apófisis Odontoides/anomalías , Apófisis Odontoides/diagnóstico por imagen , Platibasia/complicaciones , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Fusión Vertebral , Streptococcus pneumoniae , Tomografía Computarizada por Rayos X
17.
Childs Nerv Syst ; 35(6): 1089, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31025100

RESUMEN

The original version of this article unfortunately contained an error. The authors apologize to have miss looked a typo of author name "Joseph Diver". The correct name is "Joseph Driver".

18.
Neurocrit Care ; 30(1): 16-21, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29476391

RESUMEN

Seizures due to subdural hematoma (SDH) are a common finding, typically diagnosed using electroencephalography (EEG). At times, aggressive management of seizures is necessary to improve neurologic recovery and outcomes. Here, we present three patients who had undergone emergent SDH evacuation and showed postoperative focal deficits without accompanying electrographic epileptiform activity. After infarction and recurrent hemorrhage were ruled out, seizures were suspected despite a negative EEG. Patients were treated aggressively with AEDs and eventually showed clinical improvement. Long-term monitoring with EEG revealed electrographic seizures in a delayed fashion. EEG recordings are an important tool for seizure detection, but should be used as an adjunct to, rather than a replacement for, the clinical examination in the acute setting. At times, aggressive treatment of suspected postoperative seizures is warranted despite lack of corresponding electrographic activity and can improve clinical outcomes.


Asunto(s)
Hematoma Subdural/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Convulsiones/diagnóstico , Anciano de 80 o más Años , Electroencefalografía , Hematoma Subdural/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Convulsiones/etiología
19.
Childs Nerv Syst ; 34(11): 2333-2335, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29946809

RESUMEN

The authors present the case of a previously healthy 12-year-old male with intractable seizures localized to a right frontal area of encephalomalacia and porencephalic cyst who underwent resection of the seizure focus. The surgical resection cavity extended into the right lateral ventricle, and due to encountered hemorrhage, Gelfoam was used for optimal hemostasis. The patient did well following the procedure, but presented 5 months later with headaches and emesis and was discovered to have obstructive hydrocephalus on imaging studies. Endoscopic third ventriculostomy (ETV) was performed, where Gelfoam was encountered in the third ventricle, obstructing the cerebral aqueduct. After the completion of the ETV, the patient did well and continues to be asymptomatic 1 year following the procedure.


Asunto(s)
Esponja de Gelatina Absorbible/efectos adversos , Hidrocefalia/etiología , Enfermedad Iatrogénica , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/etiología , Niño , Humanos , Masculino , Convulsiones/cirugía
20.
Front Microbiol ; 9: 500, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29619015

RESUMEN

The emergence of infections caused by antimicrobial resistant microorganisms (ARMs) is currently one of the most important challenges to public health and medicine. Though speculated to originate at least partially from the overuse of antibiotics during food animal production, we hypothesized that cattle are exposed to ARMs in the environment. In this cohort study, a herd of beef calves with no previous exposure to antibiotics was followed during the first year of life in order to investigate the rate of colonization by bacteria resistant to the third-generation cephalosporin cefotaxime. Fecal samples were collected from the recto anal junction of cattle at the age of ~3, 6, 9, and 12 months and tested for cefotaxime resistant bacteria (CRB) and the presence of extended spectrum ß-lactamases (ESBLs). The colonization dynamics of CRB in calves (n = 188) was evaluated with samples collected from four periods using longitudinal statistical analyses. Colonization by CRB was a dynamic process with over 92% of the calves testing positive for CRB at least once during the first year of life. All isolates subjected to antimicrobial susceptibility test were resistant to at least four different antibiotics and carried multiple variants of the blaCTX-M genes. Metagenomic analysis revealed significant differences in microbiota of the calves with and without CRB colonization at different ages. This study provides evidence that colonization of beef calves by ARMs is a dynamic process that can occur in the absence of veterinary or agricultural use of antibiotics.

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