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Journal of the American Heart... Dec 2023Cerebral small vessel disease (cSVD) is a major contributing factor to ischemic stroke and dementia. However, the vascular pathologies of cSVD remain inconclusive. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cerebral small vessel disease (cSVD) is a major contributing factor to ischemic stroke and dementia. However, the vascular pathologies of cSVD remain inconclusive. The aim of this systematic review and meta-analysis was to characterize the associations between cSVD and cerebrovascular reactivity (CVR), cerebral autoregulation, and arterial stiffness (AS).
METHODS AND RESULTS
MEDLINE, Web of Science, and Embase were searched from inception to September 2023 for studies reporting CVR, cerebral autoregulation, or AS in relation to radiological markers of cSVD. Data were extracted in predefined tables, reviewed, and meta-analyses performed using inverse-variance random effects models to determine pooled odds ratios (ORs). A total of 1611 studies were identified; 142 were included in the systematic review, of which 60 had data available for meta-analyses. Systematic review revealed that CVR, cerebral autoregulation, and AS were consistently associated with cSVD (80.4%, 78.6%, and 85.4% of studies, respectively). Meta-analysis in 7 studies (536 participants, 32.9% women) revealed a borderline association between impaired CVR and cSVD (OR, 2.26 [95% CI, 0.99-5.14]; =0.05). In 37 studies (27 952 participants, 53.0% women) increased AS, per SD, was associated with cSVD (OR, 1.24 [95% CI, 1.15-1.33]; <0.01). Meta-regression adjusted for comorbidities accounted for one-third of the AS model variance (=29.4%, =0.02). Subgroup analysis of AS studies demonstrated an association with white matter hyperintensities (OR, 1.42 [95% CI, 1.18-1.70]; <0.01).
CONCLUSIONS
The collective findings of the present systematic review and meta-analyses suggest an association between cSVD and impaired CVR and elevated AS. However, longitudinal investigations into vascular stiffness and regulatory function as possible risk factors for cSVD remain warranted.
Topics: Humans; Female; Male; Vascular Stiffness; Cerebral Small Vessel Diseases; Risk Factors; Magnetic Resonance Imaging
PubMed: 37930079
DOI: 10.1161/JAHA.123.032616 -
Viruses Sep 2023The ability of each new SARS-CoV-2 variant to evade host humoral immunity is the focus of intense research. Each variant may also harbor unique replication capabilities...
The ability of each new SARS-CoV-2 variant to evade host humoral immunity is the focus of intense research. Each variant may also harbor unique replication capabilities relevant for disease and transmission. Here, we demonstrate a new approach to assessing viral replication kinetics using real-time cell analysis (RTCA). Virus-induced cell death is measured in real time as changes in electrical impedance through cell monolayers while images are acquired at defined intervals via an onboard microscope and camera. Using this system, we quantified replication kinetics of five clinically important viral variants: WA1/2020 (ancestral), Delta, and Omicron subvariants BA.1, BA.4, and BA.5. Multiple measures proved useful in variant replication comparisons, including the elapsed time to, and the slope at, the maximum rate of cell death. Important findings include significantly weaker replication kinetics of BA.1 by all measures, while BA.5 harbored replication kinetics at or near ancestral levels, suggesting evolution to regain replicative capacity, and both an altered profile of cell killing and enhanced fusogenicity of the Delta variant. Together, these data show that RTCA is a robust method to assess replicative capacity of any given SARS-CoV-2 variant rapidly and quantitatively, which may be useful in assessment of newly emerging variants.
Topics: Humans; SARS-CoV-2; COVID-19; Cell Death; Apoptosis
PubMed: 37766343
DOI: 10.3390/v15091937 -
Is sagittal spinopelvic alignment a cause of low back pain in pediatric spine pathologies? A review.Journal of Children's Orthopaedics Dec 2023Altered spinopelvic morphology is observed in many spine pathologies occurring during growth. The aim of the study is to better understand the sagittal compensatory... (Review)
Review
PURPOSE
Altered spinopelvic morphology is observed in many spine pathologies occurring during growth. The aim of the study is to better understand the sagittal compensatory mechanisms and their possible influence on the occurrence of pain in selected pediatric spine pathologies.
METHODS
A bibliographic search in the PubMed database included articles published between September 1965 and July 2023. The keywords contained in the search were "spondylolysis," "spondylolisthesis," "scoliosis," "kypho," "sagittal," "pediatric," "child," "adolescent," "grow," "development," and "pain."
RESULTS
The largest diversity in sagittal alignment patterns was reported in idiopathic scoliosis, with global flattening of the spine being the most common. Kyphotic deformations occurring during growth are characterized by structural thoracic or thoracolumbar kyphosis compensated by lumbar hyperlordosis and lower pelvic incidence. Whereas in spondylolisthesis, altered morphology of the spinopelvic junction with high values of pelvic incidence is observed. Pain does not seem to be related to sagittal alignment in idiopathic scoliosis. In Scheuermann disease, it is localized at the apex of the deformity and is associated with the curve pattern, whereas in spondylolisthesis, sagittal alignment correlates with pain scores only in high-grade slips.
CONCLUSION
Most of the patients with spine disorders that occurred during growth present a clinically balanced posture in the sagittal plane. It suggests that compensatory mechanisms before achieving skeletal maturity are really significant. A comprehension of sagittal alignment in spine deformities and its relationship to pain is essential for the proper assessment and treatment of these disorders.
PubMed: 38050600
DOI: 10.1177/18632521231215853 -
Journal of Children's Orthopaedics Dec 2023Low back pain in childhood was underappreciated for a long time, but recent studies report higher prevalences, up to 70%. Two of the common causes are... (Review)
Review
BACKGROUND
Low back pain in childhood was underappreciated for a long time, but recent studies report higher prevalences, up to 70%. Two of the common causes are spondylolyis/spondylolisthesis and Scheuermann's disease. These disorders are relevant in a way they both cause significant back pain, and may disrupt the sagittal spinal balance.
PURPOSE
To present the current evidence on the diagnosis, natural history and treatment of these disorders with a special focus on sagittal spinal alignment.
METHODS
This study is conducted as a literature review.
RESULTS AND CONCLUSIONS
Spondylolysis and low-grade spondylolisthesis have a benign course and are typically treated conservatively. When pars repair is indicated, pedicle screw-based techniques achieve more than 90% fusion with acceptable complication rates. High-grade spondylolisthesis, however, is frequently progressive. Surgical treatment involves fusion, which can be done in situ or after reduction. Reduction is useful for "unbalanced" patients to acquire sagittal spinopelvic balance, and it is important to distinguish these patients. Despite lowering the risk for pseudoarthrosis, reduction brings a risk for neurologic complications. With re-operation rates as high as 40%, these patients definitely require careful preoperative planning. Scheuermann's disease generally causes back pain in addition to cosmetic discomfort during adolescence. If the kyphosis is lower than 60°, symptoms typically resolve into adulthood with conservative measures only. However, it must be kept in mind that these patients may experience problems with physical performance and have a lower quality of life even when the problem seems to have "resolved". Severe kyphosis and intractable back pain are the most frequently referred surgical indications, and surgery typically involves fusion. Proper utilization of osteotomies and proper selection of the upper and lower fusion levels are of utmost importance to prevent complications in these patients.
PubMed: 38050599
DOI: 10.1177/18632521231215873 -
BMC Medical Genomics Jun 2024Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death....
BACKGROUND
Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored.
METHODS
Nasal swabs from children (< 8 months-old) infected with RSV in Rochester, NY between 1977-1998 clinically presenting with either mild or severe disease during their first cold-season were used. Whole-genome RSV sequences were obtained using overlapping PCR and next-generation sequencing. Both whole-genome phylogenetic and non-phylogenetic statistical approaches were performed to associate RSV genotype with disease severity.
RESULTS
The RSVB subtype was statistically associated with disease severity. A significant association between phylogenetic clustering of mild/severe traits and disease severity was also found. GA1 clade sequences were associated with severe disease while GB1 was significantly associated with mild disease. Both G and M2-2 gene variation was significantly associated with disease severity. We identified 16 residues in the G gene and 3 in the M2-2 RSV gene associated with disease severity.
CONCLUSION
These results suggest that phylogenetic lineage and the genetic variability in G or M2-2 genes of RSV may contribute to disease severity in young children undergoing their first infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Phylogeny; Genetic Variation; Severity of Illness Index; Infant; Respiratory Syncytial Virus, Human; Male; Genotype; Female; Genome, Viral
PubMed: 38898440
DOI: 10.1186/s12920-024-01930-7 -
PloS One 2024The COVID-19 pandemic prompted immense work on the investigation of the SARS-CoV-2 virus. Rapid, accurate, and consistent interpretation of generated data is thereby of...
The COVID-19 pandemic prompted immense work on the investigation of the SARS-CoV-2 virus. Rapid, accurate, and consistent interpretation of generated data is thereby of fundamental concern. Ontologies-structured, controlled, vocabularies-are designed to support consistency of interpretation, and thereby to prevent the development of data silos. This paper describes how ontologies are serving this purpose in the COVID-19 research domain, by following principles of the Open Biological and Biomedical Ontology (OBO) Foundry and by reusing existing ontologies such as the Infectious Disease Ontology (IDO) Core, which provides terminological content common to investigations of all infectious diseases. We report here on the development of an IDO extension, the Virus Infectious Disease Ontology (VIDO), a reference ontology covering viral infectious diseases. We motivate term and definition choices, showcase reuse of terms from existing OBO ontologies, illustrate how ontological decisions were motivated by relevant life science research, and connect VIDO to the Coronavirus Infectious Disease Ontology (CIDO). We next use terms from these ontologies to annotate selections from life science research on SARS-CoV-2, highlighting how ontologies employing a common upper-level vocabulary may be seamlessly interwoven. Finally, we outline future work, including bacteria and fungus infectious disease reference ontologies currently under development, then cite uses of VIDO and CIDO in host-pathogen data analytics, electronic health record annotation, and ontology conflict-resolution projects.
Topics: Humans; Pandemics; Biological Ontologies; Vocabulary, Controlled; Virus Diseases; Communicable Diseases; COVID-19
PubMed: 38236918
DOI: 10.1371/journal.pone.0285093 -
The Journal of Investigative Dermatology Feb 2024Tissue transcriptomics is used to uncover molecular dysregulations underlying diseases. However, the majority of transcriptomics studies focus on single diseases with... (Comparative Study)
Comparative Study
Tissue transcriptomics is used to uncover molecular dysregulations underlying diseases. However, the majority of transcriptomics studies focus on single diseases with limited relevance for understanding the molecular relationship between diseases or for identifying disease-specific markers. In this study, we used a normalization approach to compare gene expression across nine inflammatory skin diseases. The normalized datasets were found to retain differential expression signals that allowed unsupervised disease clustering and identification of disease-specific gene signatures. Using the NS-Forest algorithm, we identified a minimal set of biomarkers and validated their use as diagnostic disease classifier. Among them, PTEN was identified as being a specific marker for cutaneous lupus erythematosus and found to be strongly expressed by lesional keratinocytes in association with pathogenic type I IFNs. In fact, PTEN facilitated the expression of IFN-β and IFN-κ in keratinocytes by promoting activation and nuclear translocation of IRF3. Thus, cross-comparison of tissue transcriptomics is a valid strategy to establish a molecular disease classification and to identify pathogenic disease biomarkers.
Topics: Humans; Biomarkers; Dermatitis; Gene Expression Profiling; Keratinocytes; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; PTEN Phosphohydrolase; Skin
PubMed: 37598867
DOI: 10.1016/j.jid.2023.06.211 -
Orthopaedic Surgery Apr 2024Degenerative thoracolumbar hyperkyphosis (DTH) is a disease that negatively affects individual health and requires surgical intervention, yet the ideal surgical approach...
OBJECTIVE
Degenerative thoracolumbar hyperkyphosis (DTH) is a disease that negatively affects individual health and requires surgical intervention, yet the ideal surgical approach and complications, especially distal junctional failures (DJF), remain poorly understood. This study aims to investigate DJF in DTH and to identify the risk factors for DJF so that we can improve surgical decision-making, and advance our knowledge in the field of spinal surgery to enhance patient outcomes.
METHODS
This study retrospectively reviewed 78 cases (late osteoporotic vertebral compression fracture [OVCF], 51; Scheuermann's kyphosis [SK], 17; and degenerative disc diseases [DDD], 10) who underwent corrective surgery in our institute from 2008 to 2019. Clinical outcomes were assessed using health-related quality of life (HRQOL) measures, including the visual analogue scale (VAS) scores for back and leg pain, the Oswestry disability index (ODI), and the Japanese Orthopaedic Association (JOA) scoring system. Multiple radiographic parameters, such as global kyphosis (GK) and thoracolumbar kyphosis (TLK), were assessed to determine radiographic outcomes. Multivariate logistic regression analysis was employed to identify the risk factors associated with DJF.
RESULTS
HRQOL improved, and GK, TLK decreased at the final follow-up, with a correction rate of 67.7% and 68.5%, respectively. DJF was found in 13 of 78 cases (16.7%), two cases had wedging in the disc (L3-4) below the instrumentation, one case had a fracture of the lowest instrumented vertebrae (LIV), one case had osteoporotic fracture below the fixation, nine cases had pull-out or loosening of the screws at the LIV and three cases (23.1%) required revision surgery. The DJF group had older age, lower computed tomography Hounsfield unit (CT HU), longer follow-up, more blood loss, greater preoperative sagittal vertical axis (SVA), and poorer postoperative JOA and VAS scores (back). The change in TLK level was larger in the non-DJF group. Post-sagittal stable vertebrae (SSV) moved cranially compared with pre-SSV.
CONCLUSION
Age, CT HU, length of follow-up, estimated blood loss, and preoperative SVA were independent risk factors for DJF. We recommend fixation of the two vertebrae below the apex vertebrae for DTH to minimize surgical trauma.
Topics: Humans; Quality of Life; Retrospective Studies; Fractures, Compression; Treatment Outcome; Thoracic Vertebrae; Spinal Fractures; Kyphosis; Osteoporotic Fractures; Lumbar Vertebrae; Spinal Fusion
PubMed: 38384146
DOI: 10.1111/os.13973 -
Orthopaedic Surgery Oct 2023The proper selection of the lower instrumented vertebra (LIV) remains controversial in the surgical treatment of Scheuermann's disease and there is a paucity of studies...
OBJECTIVE
The proper selection of the lower instrumented vertebra (LIV) remains controversial in the surgical treatment of Scheuermann's disease and there is a paucity of studies investigating the clinical outcomes of fusion surgery when selecting the vertebra one level proximal to the sagittal stable vertebra (SSV-1) as LIV. The purpose of this study is to investigate whether SSV-1 could be a valid LIV for Scheuermann kyphosis (SK) patients with different curve patterns.
METHODS
This was a prospective study on consecutive SK patients treated with posterior surgery between January 2018 and September 2020, in which the distal fusion level ended at SSV-1. The LIV was selected at SSV-1 only in patients with Risser >2 and with LIV translation less than 40 mm. All of the patients had a minimum of 2-year follow-up. Patients were further grouped based on the sagittal curve pattern as thoracic kyphosis (TK, n = 23) and thoracolumbar kyphosis (TLK, n = 13). Radiographic parameters including global kyphosis (GK), lumbar lordosis (LL), sagittal vertical axis (SVA), LIV translation, pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured preoperatively, postoperatively, and at the latest follow-up. The intraoperative and postoperative complications were recorded. The Scoliosis Research Society (SRS)-22 scores were performed to evaluate clinical outcomes.
RESULTS
A total of 36 patients were recruited in this study, with 23 in the TK group and 13 in the TLK group. In TK group, the GK was significantly decreased from 80.8° ± 10.1° to 45.4° ± 7.7° after surgery, and was maintained at 45.3° ± 8.6° at the final follow-up. While in the TLK group, GK was significantly decreased from 70.7° ± 9.2° to 39.1° ± 5.4° after surgery (p < 0.001) and to 39.3° ± 4.5° at the final follow-up. Meanwhile, despite presenting with different sagittal alignment, significant improvement was observed in LL, SVA, and LIV translation for both TK and TLK groups (p < 0.05). Self-reported scores of pain and self-image in TK group and scores of self-image and function in TLK group showed significant improvement at the final follow-up (all p < 0.05). Distal junctional kyphosis (DJK) was observed in two patients (8.7%) in TK group, and one patient (7.7%) in TLK group. No revision surgery was performed.
CONCLUSION
Selecting SSV-1 as LIV can achieve satisfactory radiographic and clinical outcomes for SK patients with different curve patterns without increasing the risk of DJK. This selection strategy could be a favorable option for SK patients with Risser sign >2 and LIV translation less than 40 mm.
Topics: Humans; Scheuermann Disease; Prospective Studies; Follow-Up Studies; Thoracic Vertebrae; Retrospective Studies; Spinal Fusion; Kyphosis; Lordosis; Lumbar Vertebrae
PubMed: 37620983
DOI: 10.1111/os.13854