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Orthopaedics & Traumatology, Surgery &... Feb 2015Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or... (Review)
Review
Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with it than surgery, it should be the first-line treatment for most cases of early-onset scoliosis.
Topics: Age Factors; Age of Onset; Child; Child, Preschool; Humans; Infant; Internal Fixators; Lung; Neuromuscular Diseases; Orthopedic Procedures; Radiography; Scoliosis; Spinal Fusion; Spine
PubMed: 25623270
DOI: 10.1016/j.otsr.2014.06.032 -
The New England Journal of Medicine Feb 2021Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.
METHODS
This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.
RESULTS
The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.
CONCLUSIONS
The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).
Topics: 2019-nCoV Vaccine mRNA-1273; Adolescent; Adult; Aged; COVID-19; COVID-19 Vaccines; Female; Humans; Incidence; Male; Middle Aged; Patient Acuity; SARS-CoV-2; Single-Blind Method; Spike Glycoprotein, Coronavirus; Treatment Outcome; Young Adult
PubMed: 33378609
DOI: 10.1056/NEJMoa2035389 -
The New England Journal of Medicine Nov 2015The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain.
METHODS
We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.
RESULTS
At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group.
CONCLUSIONS
Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).
Topics: Age Factors; Aged; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Cause of Death; Female; Goals; Humans; Hypertension; Male; Middle Aged; Practice Guidelines as Topic; Risk Factors
PubMed: 26551272
DOI: 10.1056/NEJMoa1511939 -
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 -
Cureus Jul 2023Semaglutide is a class of long-acting glucagon-like peptide-1 receptor agonists (GLP1-RA) used for the treatment of type 2 diabetes mellitus (T2DM) and obesity. We...
Semaglutide is a class of long-acting glucagon-like peptide-1 receptor agonists (GLP1-RA) used for the treatment of type 2 diabetes mellitus (T2DM) and obesity. We present a 31-year-old female patient with a past medical history of T2DM without complication and no long-term or current use of insulin, class 3 obesity, hypertension, hyperlipidemia, polycystic ovary syndrome (PCOS), and anxiety, who underwent an esophagogastroduodenoscopy (EGD) in preparation for bariatric surgery while taking semaglutide. Despite appropriately following the preoperative fasting guidelines of the American Society of Anesthesiologists (ASA), endoscopy revealed food residue in the gastric body, necessitating abortion of the procedure to reduce the risk of intraoperative pulmonary aspiration. Given the lack of preoperative fasting guidelines for patients on semaglutide to date, and delayed gastric emptying being a known side effect among patients taking semaglutide, anesthesiologists should be aware of alternative methods to ensure no food is present in the stomach to mitigate the risk of pulmonary aspiration during general anesthesia.
PubMed: 37602101
DOI: 10.7759/cureus.42153 -
Nature Jun 2021Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse...
Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours. Although the role of neurons in tumour progression has previously been demonstrated, the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood, raising the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1) to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome.
Topics: Animals; Astrocytoma; Cell Adhesion Molecules, Neuronal; Cell Transformation, Neoplastic; Female; Genes, Neurofibromatosis 1; Germ-Line Mutation; Humans; Male; Membrane Proteins; Mice; Mutation; Nerve Tissue Proteins; Neurofibromin 1; Neurons; Optic Nerve; Optic Nerve Glioma; Photic Stimulation; Retina
PubMed: 34040258
DOI: 10.1038/s41586-021-03580-6 -
Nature Communications May 2022Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor...
Neuronal activity is emerging as a driver of central and peripheral nervous system cancers. Here, we examined neuronal physiology in mouse models of the tumor predisposition syndrome Neurofibromatosis-1 (NF1), with different propensities to develop nervous system cancers. We show that central and peripheral nervous system neurons from mice with tumor-causing Nf1 gene mutations exhibit hyperexcitability and increased secretion of activity-dependent tumor-promoting paracrine factors. We discovered a neurofibroma mitogen (COL1A2) produced by peripheral neurons in an activity-regulated manner, which increases NF1-deficient Schwann cell proliferation, establishing that neurofibromas are regulated by neuronal activity. In contrast, mice with the Arg1809Cys Nf1 mutation, found in NF1 patients lacking neurofibromas or optic gliomas, do not exhibit neuronal hyperexcitability or develop these NF1-associated tumors. The hyperexcitability of tumor-prone Nf1-mutant neurons results from reduced NF1-regulated hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function, such that neuronal excitability, activity-regulated paracrine factor production, and tumor progression are attenuated by HCN channel activation. Collectively, these findings reveal that NF1 mutations act at the level of neurons to modify tumor predisposition by increasing neuronal excitability and activity-regulated paracrine factor production.
Topics: Animals; Humans; Mice; Neurofibroma; Neurofibromatosis 1; Neurofibromin 1; Neurons; Optic Nerve Glioma; Peripheral Nervous System; Schwann Cells
PubMed: 35589737
DOI: 10.1038/s41467-022-30466-6 -
The New England Journal of Medicine May 2021In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected.
METHODS
We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016.
RESULTS
At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups.
CONCLUSIONS
Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062.).
Topics: Aged; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged
PubMed: 34010531
DOI: 10.1056/NEJMoa1901281 -
Science (New York, N.Y.) Feb 2007Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which...
Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns phenotypic reversibility. Can viable but defective neurons be repaired, or is the damage done during development without normal MeCP2 irrevocable? Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.
Topics: Animals; Brain; Chimera; Disease Models, Animal; Female; Gene Expression Regulation; Gene Targeting; Long-Term Potentiation; Male; Methyl-CpG-Binding Protein 2; Mice; Mice, Inbred C57BL; Neurons; Phenotype; Rett Syndrome; Synaptic Transmission; Tamoxifen; Transgenes
PubMed: 17289941
DOI: 10.1126/science.1138389 -
The New England Journal of Medicine Feb 2022NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America.
METHODS
We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed.
RESULTS
Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose.
CONCLUSIONS
NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).
Topics: Adolescent; Adult; Aged; COVID-19; COVID-19 Nucleic Acid Testing; COVID-19 Vaccines; Humans; Incidence; Male; Mexico; Middle Aged; SARS-CoV-2; Single-Blind Method; United States; Vaccine Efficacy
PubMed: 34910859
DOI: 10.1056/NEJMoa2116185