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Lancet (London, England) Jan 2021Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and... (Review)
Review
Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.
Topics: Central Nervous System Viral Diseases; Child; Enterovirus Infections; Global Health; Humans; Magnetic Resonance Imaging; Muscle Hypotonia; Muscle Weakness; Myelitis; Neuromuscular Diseases; Patient Outcome Assessment
PubMed: 33357469
DOI: 10.1016/S0140-6736(20)32723-9 -
Orthopaedics & Traumatology, Surgery &... Feb 2018Thoracic disc herniation is rare and mainly occurs between T8 and L1. The herniation is calcified in 40% of cases and is labeled as giant when it occupies more than 40%... (Review)
Review
Thoracic disc herniation is rare and mainly occurs between T8 and L1. The herniation is calcified in 40% of cases and is labeled as giant when it occupies more than 40% of the spinal canal. A surgical procedure is indicated when the patient has severe back pain, stubborn intercostal neuralgia or neurological deficits. Selection of the surgical approach is essential. Mid-line calcified hernias are approached from a transthoracic incision, while lateralized soft hernias can be approached from a posterolateral incision. The complication rate for transthoracic approaches is higher than that of posterolateral approaches; however, the former are performed in more complex herniation cases. The thoracoscopic approach is less invasive but has a lengthy learning curve. Retropleural mini-thoracotomy is a potential compromise solution. Fusion is recommended in cases of multilevel herniation, herniation in the context of Scheuermann's disease, when more than 50% bone is resected from the vertebral body, in patients with preoperative back pain or herniation at the thoracolumbar junction. Along with complications specific to the surgical approach, the surgical risks are neurological worsening, dural breach and subarachnoid-pleural fistulas. Giant calcified herniated discs are the largest contributor to myelopathy, intradural extension and postoperative complications. Some of the technical means that can be used to prevent complications are explored, along with how to address these complications.
Topics: Back Pain; Calcinosis; Diskectomy; Humans; Intervertebral Disc Displacement; Neuralgia; Patient Selection; Spinal Cord Diseases; Thoracic Vertebrae
PubMed: 29225115
DOI: 10.1016/j.otsr.2017.04.022 -
Nature Sep 2019Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used... (Comparative Study)
Comparative Study
Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used single-nucleus RNA-sequencing analysis to perform a comprehensive study of cell types in the middle temporal gyrus of human cortex. We identified a highly diverse set of excitatory and inhibitory neuron types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to similar mouse cortex single-cell RNA-sequencing datasets revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of properties of human cell types. Despite this general conservation, we also found extensive differences between homologous human and mouse cell types, including marked alterations in proportions, laminar distributions, gene expression and morphology. These species-specific features emphasize the importance of directly studying human brain.
Topics: Adolescent; Adult; Aged; Animals; Astrocytes; Biological Evolution; Cerebral Cortex; Female; Humans; Male; Mice; Middle Aged; Neural Inhibition; Neurons; Principal Component Analysis; RNA-Seq; Single-Cell Analysis; Species Specificity; Transcriptome; Young Adult
PubMed: 31435019
DOI: 10.1038/s41586-019-1506-7 -
The Journal of the American Academy of... May 2019Scheuermann's kyphosis (SK) is a rigid structural deformity of the thoracic spine defined radiographically as three or more contiguous vertebrae with at least 5° of... (Review)
Review
Scheuermann's kyphosis (SK) is a rigid structural deformity of the thoracic spine defined radiographically as three or more contiguous vertebrae with at least 5° of wedging anteriorly. Prevalence of the disease is thought to be between 0.4% and 10%. The true cause of SK remains unclear; however, various theories include growth irregularities, mechanical factors, genetic factors, and/or poor bone quality as the causes. Patients with mild disease (less than 70°) generally have a favorable prognosis with good clinical outcomes. Most patients with SK are successfully treated nonsurgically with observation, anti-inflammatory medications, and physical therapy. Surgical intervention is indicated in patients with greater than 70° to 75° thoracic curves, greater than 25° to 30° thoracolumbar curves, intractable pain, neurologic deficit, cardiopulmonary compromise, or poor cosmesis. Because of advances in posterior spinal instrumentation, surgery can typically be performed through a posterior-only approach. When surgical treatment is planned, appropriate selection of the upper- and lower-instrumented vertebrae is important to achieve a well-balanced spine, preserve motion segments, and reduce the risk of junctional kyphosis.
Topics: Anti-Inflammatory Agents; Conservative Treatment; Humans; Physical Therapy Modalities; Radiography; Scheuermann Disease; Spinal Fusion; Thoracic Vertebrae
PubMed: 30407981
DOI: 10.5435/JAAOS-D-17-00748 -
Seminars in Musculoskeletal Radiology Oct 2023Scheuermann's disease is a rigid progressive kyphosis occurring in late childhood to adolescence. It is the most common cause of sagittal imbalance and angular...
Scheuermann's disease is a rigid progressive kyphosis occurring in late childhood to adolescence. It is the most common cause of sagittal imbalance and angular progressive kyphosis in adolescents associated with back pain. The exact etiology of the disease is unclear, but it is characterized by defective growth of the end plate that may result from excessive mechanical stress on a weakened end plate during spinal growth. Several other theories have been proposed, and it is thought to be a multifactorial disease occurring as a result of the interplay of multiple factors. The radiographic features consist of anterior vertebral body wedging, irregular end plates, Schmorl's nodes, and intervertebral disk degeneration. The natural history and evolution of this disease is also unknown. Conservative management with physiotherapy, rehabilitation, and bracing is the first line of treatment. Mechanical bracing helps prevent further progression of the kyphotic deformity. Surgery is mostly indicated in patients with failure of conservative management, with neurologic compromise, and for cosmetic reasons.
Topics: Adolescent; Humans; Child; Scheuermann Disease; Spine
PubMed: 37816360
DOI: 10.1055/s-0043-1771334 -
The Open Orthopaedics Journal 2017The review evaluates the up-to-date evidence for the treatment of spinal deformities, including scoliosis and hyperkyphosis in adolescents and adults. (Review)
Review
INTRODUCTION
The review evaluates the up-to-date evidence for the treatment of spinal deformities, including scoliosis and hyperkyphosis in adolescents and adults.
MATERIAL AND METHODS
The PubMed database was searched for review articles, prospective controlled trials and randomized controlled trials related to the treatment of spinal deformities. Articles on syndromic scoliosis were excluded and so were the articles on hyperkyphosis of the spine with causes other than Scheuermann's disease and osteoporosis. Articles on conservative and surgical treatments of idiopathic scoliosis, adult scoliosis and hyperkyphosis were also included. For retrospective papers, only studies with a follow up period exceeding 10 years were included.
RESULTS
The review showed that early-onset idiopathic scoliosis has a worse outcome than late-onset idiopathic scoliosis, which is rather benign. Patients with AIS function well as adults; they have no more health problems when compared to patients without scoliosis, other than a slight increase in back pain and aesthetic concern. Conservative treatment of adolescent idiopathic scoliosis (AIS) using physiotherapeutic scoliosis-specific exercises (PSSE), specifically PSSR and rigid bracing was supported by level I evidence. Yet to date, there is no high quality evidence (RCT`s) demonstrating that surgical treatment is superior to conservative treatment for the management of AIS. For adult scoliosis, there are only a few studies on the effectiveness of PSSEs and a conclusion cannot as yet be drawn.For hyperkyphosis, there is no high-quality evidence for physiotherapy, bracing or surgery for the treatment of adolescents and adults. However, bracing has been found to reduce thoracic hyperkyphosis, ranging from 55 to 80° in adolescents. In patients over the age of 60, bracing improves the balance score, and reduces spinal deformity and pain. Surgery is indicated in adolescents and adults in the presence of progression of kyphosis, refractory pain and loss of balance.
DISCUSSION
The available evidence reviewed has suggested that different approaches are needed towards the management of different spinal deformities. Specific exercises should be prescribed in children and adolescents with a Cobb angle in excess of 15°. In progressive curves, they should be used in conjunction with bracing. Clarity regarding differences and similarities is given as to what makes PSSE and PSSR specific exercises. As AIS is relatively benign in nature, conservative treatment should be tried when the curve is at a surgical threshold, before surgery is considered. Similarly, bracing and exercises should be prescribed for patients with hyperkyphosis, particularly when the lumbar spine is afflicted. Surgery should be considered only when the symptoms cannot be managed conservatively.
CONCLUSION
There is at present high quality evidence in support of the conservative treatment of AIS. The current evidence supports the use of PSSE, especially those using PSSR, together with bracing in the treatment of AIS. In view of the lack of medical consequences in adults with AIS, conservative treatment should be considered for curves exceeding the formerly assumed range of conservative indications.There is, however a lack of evidence in support of any treatment of choice for hyperkyphosis in adolescents and spinal deformities in adults. Yet, conservative treatment should be considered first. Yet to date, there is no high quality evidence (RCT`s) demonstrating that surgical treatment is superior to conservative treatment for the management of AIS and hyperkyphosis. Additionally, surgery needs to be considered with caution, as it is associated with a number of long-term complications.
PubMed: 29399227
DOI: 10.2174/1874325001711011521 -
Nature May 2022The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection... (Review)
Review
The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.
Topics: Animals; Biological Evolution; COVID-19; COVID-19 Vaccines; Humans; National Institute of Allergy and Infectious Diseases (U.S.); Pandemics; Pharmacogenomic Variants; SARS-CoV-2; United States; Virulence
PubMed: 35361968
DOI: 10.1038/s41586-022-04690-5 -
Nature Immunology Oct 2023Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC... (Review)
Review
Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a 'reservoir'. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; RNA, Viral; SARS-CoV-2; Antiviral Agents; Disease Progression
PubMed: 37667052
DOI: 10.1038/s41590-023-01601-2 -
Nature Medicine May 2021Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in...
Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.
Topics: Angiotensin-Converting Enzyme 2; Asymptomatic Infections; COVID-19; Humans; Mouth; SARS-CoV-2; Saliva; Serine Endopeptidases; Taste Disorders; Virus Replication
PubMed: 33767405
DOI: 10.1038/s41591-021-01296-8 -
Der Orthopade Apr 2022Scheuermann's disease represents the second most common deformity of the growing spine after the various forms of scoliosis. In cases of early diagnosis and mild...
Scheuermann's disease represents the second most common deformity of the growing spine after the various forms of scoliosis. In cases of early diagnosis and mild kyphotic deformity conservative treatment with a brace and physiotherapy shows very good results; however, in cases of neurologic deficits, curve progression despite conservative treatment and increasing pain symptoms with a Stagnara angle of more than 70-75°, surgical treatment is meaningful. The surgical strategy can include posterior spondylodesis with prior anterior release or posterior instrumentation with posterior column osteotomy depending on the surgeon's experience. The choice of the extent of the operation with the vertebrae to be instrumented and including the straightening method should be oriented to the avoidance of complications, such as proximal or distal junctional kyphosis.
Topics: Humans; Osteotomy; Scheuermann Disease; Scoliosis; Spinal Fusion; Spine
PubMed: 35290495
DOI: 10.1007/s00132-022-04239-4