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BACKGROUND: Far lateral (extraforaminal) disc herniations comprise approximately 10% of symptomatic lumbar disc herniations. They represent operative challenges due to accessibility and surgical unfamiliarity. Surgical strategies in the past have included open discectomy and posterior lumbar interbody fusion. Tubular microdiscectomies have gained traction due to their minimally invasive advantages, including reduced morbidity, pain and length of hospital stay. METHODS: We report our retrospective single institution consecutive case series of tubular far lateral microdiscectomies. One hundred and seventy-six patients were operated on over an eight-year period. Clinical outcomes were assessed after institutional ethics approval. We additionally describe our surgical technique with an illustrative video case. RESULTS: Over a mean follow-up of 21 weeks, 77% of patients had good or excellent clinical outcomes according to the MacNab criteria. 12% of patients underwent reoperation at the index level for symptom recurrence or persistence. Mean length of hospital stay was 1.3 days. There was a 1% rate of both postoperative haematoma and infection. Mean operation duration was 86 minutes. CONCLUSION: This case series represents the largest currently reported in the literature. Minimally invasive microdiscectomies performed through tubes allow for precise localisation, reduced tissue disruption and favourable clinical outcomes. Our results appear consistent with a review of the literature, demonstrating the safety and efficacy of this approach.
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Background: Missouri's Overdose Field Report (ODFR) is a community-based reporting system which intends to capture overdoses which may not be otherwise recorded.Objectives: Describe the factors related to non-fatal overdoses reported to Missouri's ODFR.Methods: This study used a descriptive epidemiological approach to examine the demographics and circumstances of overdoses reported to the ODFR. We used binary logistic regression to evaluate factors associated with survival and ordinal logistic regression to evaluate factors associated with number of doses used. Factors were chosen based on their relevance to overdose education and survival, and naloxone distribution.Results: Between 2018 and 2022, 12,225 overdoses (67% male; 78% White) were reported through the ODFR, with a 96% (n = 11,225) survival rate. Overdose survival (ps < .02) was associated with younger age (OR = .58), no opioid and stimulant co-involvement (OR = .61), and private location (OR = .48). Intramuscular naloxone in particular was associated with a significantly higher odds of survival compared to nasal naloxone (OR = 2.11). An average of 1.6 doses of naloxone per incident were administered. Additional doses were associated (ps < .02) with being older (OR = .45), female (OR = .90), nasal naloxone (versus intravenous) (OR = .65), and the belief fentanyl was present (OR = 1.49).Conclusion: Our reporting form provides a comprehensive picture of the events surrounding reported overdoses, including factors associated with survival, how much naloxone was used, and the effects of respondents believing fentanyl was involved. Missouri's report can provide support for current naloxone dosing, contextualize refusing post-overdose transport, and can be used to improve overdose response by community and first responders.
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Overdose de Drogas , Naloxona , Antagonistas de Entorpecentes , Humanos , Naloxona/uso terapêutico , Naloxona/administração & dosagem , Feminino , Masculino , Overdose de Drogas/mortalidade , Overdose de Drogas/epidemiologia , Missouri/epidemiologia , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Antagonistas de Entorpecentes/uso terapêutico , Antagonistas de Entorpecentes/administração & dosagem , Adolescente , Inquéritos e Questionários , Analgésicos Opioides/intoxicação , Analgésicos Opioides/administração & dosagem , Taxa de Sobrevida , IdosoRESUMO
Community-engaged patient navigation safety net programs are established as an evidence-based approach to address cancer prevention and early detection efforts, but barriers to expand and sustain such programs persist. In addition, few studies describe how these programs impact buy-in among communities and policy change within health care systems and government. We describe how we used the Capacity for Sustainability Framework to guide efforts for program sustainability and community, institutional, and policy level change in a breast cancer screening and patient navigation safety net program. The nine domains of the Capacity for Sustainability Framework were used to develop program logic models, to inform program implementation and quality improvement agendas, and to guide multi-level partner and stakeholder engagement, outreach, and dissemination of outcomes. The program is currently in its seventh year and continues to be annually funded by a city public health department. In 2021, additional 5-year renewable funding from a state public health department was secured. In addition, institutional program support was expanded for patients diagnosed with breast cancer. Program leaders worked with policymakers to draft legislation to support training certification and third-payor reimbursement for patient navigators and community health workers. The program is well-known and trusted among community members, community-based organizations, and providers. Community, organizational, and policy-level outcomes demonstrate that community-engaged patient navigation safety net programs can influence more than individual and interpersonal outcomes and can be sustained over time.
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Neoplasias da Mama , Detecção Precoce de Câncer , Avaliação de Programas e Projetos de Saúde , Provedores de Redes de Segurança , Humanos , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/diagnóstico , Feminino , Provedores de Redes de Segurança/organização & administração , Navegação de Pacientes/organização & administração , Política de SaúdeRESUMO
Haematinic deficiency is not uncommon in pregnancy. Folate deficiency is more common than B12 deficiency because of the increased uptake of folate in pregnancy, and the fact that B12 stores take much longer to deplete. Described here are five cases of anaemia in pregnancy secondary to severe haematinic deficiency with subsequent management and pregnancy outcomes. In the majority of cases, the women were proteinuric, but systemically well and normotensive. Thrombotic thrombocytopenic purpura and HELLP were both considered, but the identification of very abnormal folate levels of less than 3 µg/L in all and low B12 deficiency in the majority made haematinic deficiency the most likely diagnosis. They all received high dose folic acid, parenteral vitamin B12 and oral iron and made good haematological recoveries. Adequate antenatal correction of vitamin deficiency like this avoids bone marrow suppression and helps minimise poor obstetric outcomes associated with pre-existing anaemia including post-partum haemorrhage.
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Research suggests that adiponectin, leptin, and genetic polymorphisms such as catechol-O-methyltransferase (COMT) genotype may play an integral role in blood pressure status and thereby cardiovascular health. This is an area especially important for women who are post-menopause; however, the current literature investigating these associations is limited. This study was a cross-sectional secondary analysis of baseline data (N 237) from the Minnesota Green Tea Trial (MGTT). The current study explored the relationships between plasma adiponectin, leptin, and COMT genotype on blood pressure measures. Plasma adiponectin and leptin were obtained after an overnight fast of at least 10 h and were measured by the radioimmunoassay method. The relationships were analysed using multiple linear regression after adjusting for potential confounders. Effect modifications by age, body mass index (BMI) category, blood pressure category, antihypertensive medication use, and COMT genotype were also investigated. The majority of participants were non-Hispanic (97â 9 %) and Caucasian (94â 9 %). Mean (sd) age and BMI were 60â 7 (5â 0) years and 28â 2 (2â 9) kg/m2, respectively. After adjustment for confounding variables, neither plasma adiponectin, plasma leptin nor COMT genotype was associated with systolic or diastolic blood pressure measures. The results of stratified analyses also did not reveal any significant interactions or associations. Based on the findings of this study, which utilised more rigorous statistical methods than previous research, neither adiponectin, leptin nor COMT genotype play a role in blood pressure measures in women who are post-menopause.
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Myofibroblastoma (MFB) of the breast is a rare benign neoplasm of the mammary stroma. Several morphologic variants have been described in the literature, which can create diagnostic challenges for pathologists, in particular the epithelioid variant of MFB, which can mimic invasive lobular carcinoma. We report a case of a 72-year-old female who presented for a painless breast lump and was later found to have 2 lesions on imaging, with 1 lesion corresponding to the palpable lump and the other lying in a different quadrant. Core-needle biopsies demonstrated ductal carcinoma in-situ at both lesional sites with what was originally felt to be an invasive lobular carcinoma at the lesional site which did not correspond to the palpable lump. After mastectomy, with more complete visualization microscopically of the lesional area originally felt to be an invasive lobular carcinoma, the final pathology was consistent with a MFB, predominantly epithelioid variant, in addition to ductal carcinoma in-situ and lobular carcinoma in-situ. In this paper we describe the imaging findings of an epithelioid MFB and how its nonspecific nature necessitates close communication between the radiologist and pathologist to make the correct diagnosis.
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Invasive breast carcinoma of no special type (IBC-NST) with medullary pattern is an uncommon histologic type of invasive breast carcinoma. It is associated with high-grade, poorly differentiated tumor cells that form large sheets of irregular confluent tumor cells associated with a prominent lymphocytic infiltrate. Patients with IBC-NST with medullary pattern are often postmenopausal women with a high body mass index and multiparity. We report the case of a 71-year-old woman who presented for routine screening mammography and breast mass suspicious for malignancy, initially thought to be invasive ductal carcinoma with an associated prominent lymphoid infiltrate. However, it was ultimately diagnosed as IBC-NST with medullary pattern, and radiologic imaging (particularly ultrasound and mammography) along with pathology review were critical in making the diagnosis. We make the case of the importance of radiographic imaging in diagnosing this condition, as the prognosis of IBC-NST with medullary pattern is typically more favorable compared to IBC-NST.
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High maternal weight is associated with detrimental outcomes in offspring, including increased susceptibility to neurological disorders such as anxiety, depression and communicative disorders. Despite widespread acknowledgement of sex biases in the development of these disorders, few studies have investigated potential sex-biased mechanisms underlying disorder susceptibility. Here, we show that a maternal high-fat diet causes endotoxin accumulation in fetal tissue, and subsequent perinatal inflammation contributes to sex-specific behavioural outcomes in offspring. In male offspring exposed to a maternal high-fat diet, increased macrophage Toll-like receptor 4 signalling results in excess microglial phagocytosis of serotonin (5-HT) neurons in the developing dorsal raphe nucleus, decreasing 5-HT bioavailability in the fetal and adult brains. Bulk sequencing from a large cohort of matched first-trimester human samples reveals sex-specific transcriptome-wide changes in placental and brain tissue in response to maternal triglyceride accumulation (a proxy for dietary fat content). Further, fetal brain 5-HT levels decrease as placental triglycerides increase in male mice and male human samples. These findings uncover a microglia-dependent mechanism through which maternal diet can impact offspring susceptibility for neuropsychiatric disorder development in a sex-specific manner.
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Placenta , Serotonina , Gravidez , Masculino , Feminino , Camundongos , Animais , Humanos , Encéfalo , Dieta Hiperlipídica/efeitos adversos , Gorduras na DietaRESUMO
Antibiotic resistance is a growing problem facing global societies today. Many new antibiotics are derivatized versions of already existing antibiotics, which allows for antibiotic resistance to arise. To combat this issue, new antibiotics with different core structures need to be elucidated. Asymmetrical polyacetylenes have been isolated from natural products and they have previously been demonstrated to exhibit antimicrobial and antibacterial activity; however, their synthetic preparation has not made them easily amenable to rapid derivatization for SAR studies. Using a combination of solution and solid-supported chemistries, an array of diynes inspired by a known natural product were prepared and assessed for antibacterial activity. Ultimately, several compounds were identified with improved activity in bacterial viability assays. Moreover, some compounds were discovered that displayed a degree of specificity for E. coli over P. fluorescens and vice versa. These new compounds show promise, and further investigation is needed to pinpoint the specific structural components that elicit biological activity.
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Produtos Biológicos , Di-Inos , Escherichia coli , Poli-Inos , Antibacterianos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Endotoxin accumulation has been widely noted in several pathologies ranging from metabolic dysregulation to bacterial infection. Using limulus amebocyte lysate (LAL) assays to detect endotoxin load has been the only reliable way to assess endotoxin accumulation, but assays optimized for detection in opaque tissues are still lacking. We optimized a sensitive Kinetic LAL assay for endotoxin detection from murine tissues. In this protocol, we describe tissue collection and homogenization, followed by the procedure to run the assay and data analysis. For complete details on the use and execution of this protocol, please refer to Ceasrine et al. (2022).
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Endotoxinas , Caranguejos Ferradura , Animais , Camundongos , Endotoxinas/análise , Teste do Limulus/métodos , Bioensaio , CinéticaRESUMO
Microglia are the resident macrophages of the CNS that serve critical roles in brain construction. Although human brains contain microglia by 4 weeks gestation, an understanding of the earliest microglia that seed the brain during its development remains unresolved. Using time-lapse imaging in zebrafish, we discovered a mrc1a+ microglia precursor population that seeds the brain before traditionally described microglia. These early microglia precursors are dependent on lymphatic vasculature that surrounds the brain and are independent of pu1+ yolk sac-derived microglia. Single-cell RNA-sequencing datasets reveal Mrc1+ microglia in the embryonic brains of mice and humans. We then show in zebrafish that these early mrc1a+ microglia precursors preferentially expand during pathophysiological states in development. Taken together, our results identify a critical role of lymphatics in the microglia precursors that seed the early embryonic brain.
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Microglia , Peixe-Zebra , Animais , Encéfalo/fisiologia , Humanos , Microglia/metabolismo , Saco Vitelino/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Oligodendrocytes are the myelinating cell of the CNS and are critical for the functionality of the nervous system. In the packed CNS, we know distinct profiles of oligodendrocytes are present. Here, we used intravital imaging in zebrafish to identify a distinct oligodendrocyte lineage cell (OLC) that resides on the dorsal root ganglia sensory neurons in the spinal cord. Our profiling of OLC cellular dynamics revealed a distinct cell cluster that interacts with peripheral sensory neurons at the dorsal root entry zone (DREZ). With pharmacological, physical and genetic manipulations, we show that the entry of dorsal root ganglia pioneer axons across the DREZ is important to produce sensory located oligodendrocyte lineage cells. These oligodendrocyte lineage cells on peripherally derived sensory neurons display distinct processes that are stable and do not express mbpa. Upon their removal, sensory behavior related to the DRG neurons is abolished. Together, these data support the hypothesis that peripheral neurons at the DREZ can also impact oligodendrocyte development.
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Little is known on how mild traumatic brain injury affects white matter based on age at injury, sex, cerebral microbleeds, and time since injury. Here, we study the fractional anisotropy of white matter to study these effects in 109 participants aged 18-77 (46 females, age µ ± σ = 40 ± 17 years) imaged within [Formula: see text] 1 week and [Formula: see text] 6 months post-injury. Age is found to be linearly associated with white matter degradation, likely due not only to injury but also to cumulative effects of other pathologies and to their interactions with injury. Age is associated with mean anisotropy decreases in the corpus callosum, middle longitudinal fasciculi, inferior longitudinal and occipitofrontal fasciculi, and superficial frontal and temporal fasciculi. Over [Formula: see text] 6 months, the mean anisotropies of the corpus callosum, left superficial frontal fasciculi, and left corticospinal tract decrease significantly. Independently of other predictors, age and cerebral microbleeds contribute to anisotropy decrease in the callosal genu. Chronically, the white matter of commissural tracts, left superficial frontal fasciculi, and left corticospinal tract degrade appreciably, independently of other predictors. Our findings suggest that large commissural and intra-hemispheric structures are at high risk for post-traumatic degradation. This study identifies detailed neuroanatomic substrates consistent with brain injury patients' age-dependent deficits in information processing speed, interhemispheric communication, motor coordination, visual acuity, sensory integration, reading speed/comprehension, executive function, personality, and memory. We also identify neuroanatomic features underlying white matter degradation whose severity is associated with the male sex. Future studies should compare our findings to functional measures and other neurodegenerative processes.
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Lesões Encefálicas Traumáticas , Substância Branca , Idoso , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , Hemorragia Cerebral/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Substância Branca/diagnóstico por imagemRESUMO
Transgender women are increasingly evaluated in breast imaging centers. Radiologists should be familiar with a range of imaging findings related to feminizing hormone therapy and breast augmentations as well as benign and malignant lesions seen in this population. A growing body of literature has suggested that feminizing hormone therapy may increase the risk of breast cancer, prompting professional organizations to develop screening guidelines. The aim of this paper is to review common breast imaging findings in transgender women, recent data on the association between feminizing hormone therapy and breast cancer, and guidelines for breast cancer screening. Knowing these unique imaging features in transgender women is essential for providing competent care and reducing health care disparities.
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Neoplasias da Mama , Pessoas Transgênero , Transexualidade , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Feminino , Identidade de Gênero , HumanosRESUMO
Axillary adenopathy is a potential side effect following COVID-19 vaccination. We report four cases of axillary adenopathy in the setting of recent COVID-19 vaccination (Moderna and Pfizer-BioNTech) at our institution. Our cases show unilateral axillary adenopathy, as well as adenopathy persisting for two to three weeks following vaccination. The Society of Breast Imaging (SBI) and Harvard University have each released guidelines for management of axillary adenopathy following COVID-19 vaccination. While SBI recommends short term imaging 4-12 weeks following the second dose, a group of physicians from Harvard suggest clinical follow-up with sonographic imaging if clinical concern persists beyond six weeks. As a larger percentage of the general population becomes vaccinated, it is important for radiologists to be aware of potential vaccine-induced ipsilateral axillary adenopathy on screening and diagnostic breast imaging to reduce the number of unnecessary biopsies performed in this patient population.
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COVID-19 , Linfadenopatia , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Vacinação/efeitos adversosRESUMO
Axons navigate through the embryo to construct a functional nervous system. A missing part of the axon navigation puzzle is how a single axon traverses distinct anatomic choice points through its navigation. The dorsal root ganglia (DRG) neurons experience such choice points. First, they navigate to the dorsal root entry zone (DREZ), then halt navigation in the peripheral nervous system to invade the spinal cord, and then reinitiate navigation inside the CNS. Here, we used time-lapse super-resolution imaging in zebrafish DRG pioneer neurons to investigate how embryonic axons control their cytoskeleton to navigate to and invade at the correct anatomic position. We found that invadopodia components form in the growth cone even during filopodia-based navigation, but only stabilize when the axon is at the spinal cord entry location. Further, we show that intermediate levels of DCC and cAMP, as well as Rac1 activation, subsequently engage an axon invasion brake. Our results indicate that actin-based invadopodia components form in the growth cone and disruption of the invasion brake causes axon entry defects and results in failed behavioral responses, thereby demonstrating the importance of regulating distinct actin populations during navigational challenges.SIGNIFICANCE STATEMENT Correct spatiotemporal navigation of neuronal growth cones is dependent on extracellular navigational cues and growth cone dynamics. Here, we link dcc-mediated signaling to actin-based invadopodia and filopodia dynamics during pathfinding and entry into the spinal cord using an in vivo model of dorsal root ganglia (DRG) sensory axons. We reveal a molecularly-controlled brake on invadopodia stabilization until the sensory neuron growth cone is present at the dorsal root entry zone (DREZ), which is ultimately essential for growth cone entry into the spinal cord and behavioral response.
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Orientação de Axônios/fisiologia , Receptor DCC/metabolismo , Transdução de Sinais/fisiologia , Proteínas de Peixe-Zebra/metabolismo , Animais , Gânglios Espinais/embriologia , Peixe-ZebraRESUMO
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) and late-onset idiopathic aqueductal stenosis (LIAS) are two forms of chronic adult hydrocephalus of different aetiology. We analysed overnight intracranial pressure (ICP) monitoring to elucidate ICP waveform changes characteristic for iNPH and LIAS to better understand pathophysiological processes of both diseases. METHODS: 98 patients with iNPH and 14 patients with LIAS from two neurosurgical centres were included. All patients underwent diagnostic overnight computerised ICP monitoring with calculation of mean ICP, ICP heartbeat related pulse wave amplitude calculated in the frequency domain (AMP) and the time domain (MWA), index of cerebrospinal compensatory reserve (RAP) and power of slow vasogenic waves (SLOW). RESULTS: ICP was higher in LIAS than iNPH patients (9.3 ± 3.0 mmHg versus 5.4 ± 4.2 mmHg, p = 0.001). AMP and MWA were higher in iNPH versus LIAS (2.36 ± 0.91 mmHg versus 1.81 ± 0.59 mmHg for AMP, p = 0.012; 6.0 ± 2.0 mmHg versus 4.9 ± 1.2 mmHg for MWA, p = 0.049). RAP and SLOW indicated impaired reserve capacity and compliance in both diseases, but did not differ between groups. INPH patients were older than LIAS patients (77 ± 6 years versus 54 ± 14 years, p < 0.001). CONCLUSIONS: ICP is higher in LIAS than in iNPH patients, likely due to the chronically obstructed CSF flow through the aqueduct, but still in a range considered normal. Interestingly, AMP/MWA was higher in iNPH patients, suggesting a possible role of high ICP pulse pressure amplitudes in iNPH pathophysiology. Cerebrospinal reserve capacity and intracranial compliance is impaired in both groups and the pressure-volume relationship might be shifted towards lower ICP values in iNPH. The physiological influence of age on ICP and AMP/MWA requires further research.
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Pressão Sanguínea/fisiologia , Hidrocefalia de Pressão Normal/epidemiologia , Hidrocefalia de Pressão Normal/fisiopatologia , Hidrocefalia/epidemiologia , Hidrocefalia/fisiopatologia , Pressão Intracraniana/fisiologia , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Gestational hypertensive and acute hypotensive disorders are associated with maternal morbidity and mortality worldwide. However, physiological blood pressure changes in pregnancy are insufficiently defined. We describe blood pressure changes across healthy pregnancies from the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Fetal Growth Longitudinal Study (FGLS) to produce international, gestational age-specific, smoothed centiles (third, 10th, 50th, 90th, and 97th) for blood pressure. METHODS AND FINDINGS: Secondary analysis of a prospective, longitudinal, observational cohort study (2009 to 2016) was conducted across 8 diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States of America. We enrolled healthy women at low risk of pregnancy complications. We measured blood pressure using standardised methodology and validated equipment at enrolment at <14 weeks, then every 5 ± 1 weeks until delivery. We enrolled 4,607 (35%) women of 13,108 screened. The mean maternal age was 28·4 (standard deviation [SD] 3.9) years; 97% (4,204/4,321) of women were married or living with a partner, and 68% (2,955/4,321) were nulliparous. Their mean body mass index (BMI) was 23.3 (SD 3.0) kg/m2. Systolic blood pressure was lowest at 12 weeks: Median was 111.5 (95% CI 111.3 to 111.8) mmHg, rising to a median maximum of 119.6 (95% CI 118.9 to 120.3) mmHg at 40 weeks' gestation, a difference of 8.1 (95% CI 7.4 to 8.8) mmHg. Median diastolic blood pressure decreased from 12 weeks: 69.1 (95% CI 68.9 to 69.3) mmHg to a minimum of 68.5 (95% CI 68.3 to 68.7) mmHg at 19+5 weeks' gestation, a change of -0·6 (95% CI -0.8 to -0.4) mmHg. Diastolic blood pressure subsequently increased to a maximum of 76.3 (95% CI 75.9 to 76.8) mmHg at 40 weeks' gestation. Systolic blood pressure fell by >14 mmHg or diastolic blood pressure by >11 mmHg in fewer than 10% of women at any gestational age. Fewer than 10% of women increased their systolic blood pressure by >24 mmHg or diastolic blood pressure by >18 mmHg at any gestational age. The study's main limitations were the unavailability of prepregnancy blood pressure values and inability to explore circadian effects because time of day was not recorded for the blood pressure measurements. CONCLUSIONS: Our findings provide international, gestational age-specific centiles and limits of acceptable change to facilitate earlier recognition of deteriorating health in pregnant women. These centiles challenge the idea of a clinically significant midpregnancy drop in blood pressure.