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Nature Immunology Oct 2023
PubMed: 37723351
DOI: 10.1038/s41590-023-01646-3 -
European Journal of Physical and... Aug 2023In the literature, there are several papers on Scheuermann's kyphosis. It is a structural deformity of the spine that is characterized by anterior wedging of 5° or more... (Observational Study)
Observational Study
BACKGROUND
In the literature, there are several papers on Scheuermann's kyphosis. It is a structural deformity of the spine that is characterized by anterior wedging of 5° or more of 3 adjacent thoracic vertebral bodies with kyphosis measuring greater than 45° between T5 and T12. Bracing treatment is able to obtain, during skeletal growth, remodeling of the deformed vertebrae.
AIM
The aim of this study was to evaluate the effectiveness of conservative treatment in Scheuermann's kyphosis at a minimum follow-up of 10 years.
DESIGN
This is an observational controlled cohort study nested in a prospective clinical on-going database in patients with Scheuermann kyphosis.
SETTING
Inpatients and outpatients in Rome.
METHODS
From a consecutive series of patients included in a prospective database, we selected 158 patients with thoracic Scheuermann's kyphosis who were treated using an anti-gravity brace: 93 males and 65 females. The mean age at the beginning of the treatment was 14 years. The time bracing prescribed was a max of 20 hours daily and a min of 16 hours daily. Weaning was started when a full recovery of vertebral geometry was seen on a lateral radiograph view or when growing was ended. Radiographical measurements were performed on radiographs from a lateral projection at baseline (t1), at the end of the treatment (t2) and at 10 years of minimum follow-up (t3). To avoid the great variance in the range of curve angles in thoracic kyphosis (TK) that rely on the radiological position, X-rays were performed observing the following position: standing with head straight, arms bent at 45° and hands lightly placed on a support. The anterior wedging angle (Alpha) of the apex vertebra and the degrees of the curve (Cobb methods) were analyzed using statistical analysis.
RESULTS
The results from our study showed that in 158 patients with TK curves, the mean Cobb angle was 57.6±6.3 SD at baseline, 43.3±7.8 SD at the end of treatment and 44.49±7.4 SD at ten years of follow-up. The alpha angle was 14.43±2.535 SD at baseline and 8.571±3.589 SD at the end of treatment, and after ten years of follow-up, it was 8.654±3.57 SD. The mean duration of treatment was 28.42±12.07 months, and the mean follow-up was 128.3±11.07 months. The difference between baseline and end of treatment, tested with the one-way ANOVA comparisons test, was significant (P<0.0001) for both Cobb angle and alpha; instead, the difference between the end of treatment and follow-up was not significant (P=0.3277).
CONCLUSIONS
The results confirm that conservative treatment in Scheuermann's kyphosis during skeletal growth is effective. Bracing treatment can remodel the deformed vertebrae.
CLINICAL REHABILITATION IMPACT
At the 10-year follow-up after bracing, kyphosis curve correction was stable over time.
Topics: Female; Male; Humans; Adolescent; Scheuermann Disease; Cohort Studies; Research Design; Conservative Treatment; Thoracic Vertebrae
PubMed: 37746785
DOI: 10.23736/S1973-9087.23.08070-X -
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 -
European Spine Journal : Official... Mar 2024To determine optimal proximal fusion levels for instrumented spinal fusion for Scheuermann kyphosis. (Review)
Review
OBJECTIVE
To determine optimal proximal fusion levels for instrumented spinal fusion for Scheuermann kyphosis.
METHODS
We reviewed 86 patients (33 women) who underwent corrective instrumented spinal fusion for Scheuermann kyphosis. All patients had long-cassette upright lateral radiographs taken preoperatively, postoperatively, and at 2 years and the last follow-up. Demographic, radiographic, and surgical parameters were compared between patients with and without PJK.
RESULTS
PJK occurred in 28 patients (32%). The mean maximum Cobb angle was 85.8° ± 11.7° preoperatively, 54.8° ± 14.2° postoperatively, and 59.7° ± 16.8° at the last follow-up. Age and sex did not differ between the PJK and non-PJK groups (P > 0.05). The preoperative curve characteristics, fusion levels, and corrective ratio were similar in both groups (P > 0.05). The maximal Cobb angle at 2 years and the last follow-up significantly differed between the 2 groups (P < 0.05). The proportion of patients with the uppermost instrumented vertebra (UIV) at or above the proximal end vertebra (PEV) was similar in both groups (P > 0.05). The proportion of patients with UIV at or above T2 was significantly greater in the non-PJK group (P < 0.05). PJK was significantly associated with a C7 plumb line (C7PL)-sacrum distance ≥ 50 mm (P < 0.05).
CONCLUSION
PJK is the main cause of postoperative correction loss. Proper fusion-level selection can reduce PJK occurrence. We recommend having the UIV at T2 or above, especially when the C7PL-sacrum distance ≥ 50 mm.
Topics: Humans; Female; Scheuermann Disease; Kyphosis; Follow-Up Studies; Retrospective Studies; Sacrum; Spinal Fusion; Postoperative Complications; Risk Factors
PubMed: 37955752
DOI: 10.1007/s00586-023-08029-0 -
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 -
International Journal of Surgery Case... Aug 2023Scheuermann's kyphosis is a structural deformity of the thoracolumbar spine that is classified in typical (thoracic) and atypical (lumbar and thoracolumbar)...
INTRODUCTION AND IMPORTANCE
Scheuermann's kyphosis is a structural deformity of the thoracolumbar spine that is classified in typical (thoracic) and atypical (lumbar and thoracolumbar) Scheuermann's disease. Surgical intervention is reserved for those with progressive kyphosis, intractable pain and neurological impairment. Although, previous literature focuses on the correction of the thoracic kyphosis (TK), recent lines of evidence recommend considering all the sagittal balance parameters when performing a surgery. We herein, report a posterior-only approach in a patient with Scheuermann's kyphosis, considering all the sagittal balance parameters.
CASE PRESENTATION
The patient was a 17-year-old boy with a kyphotic deformity in the lumbar region, with urinary retention and upper back intractable pain. The preoperative physical examination was normal except for a kyphotic gait. The patient was first treated with thoracic lumbosacral orthoses (TLSO) brace that was not effective; consequently, the patient underwent posterior only approach (pedicular screw fixation along with Smith-Peterson osteotomy) with correction of the sagittal balance and kyphosis. The patient's sign and symptoms improved significantly. The surgery was uneventful and no complication was recorded. The 1-year follow-up revealed normal neurological examination and normal sagittal balance parameters.
CLINICAL DISCUSSION
Atypical Scheuermann's kyphosis with neurological impairment and progressive kyphosis should be treated with surgical intervention.
CONCLUSION
Considering the sagittal parameters of the spine, the surgical intervention should be designed to correct the kyphosis and the other indices of the sagittal balance. Posterior-only approach is safe and effective method for correction of the TK and improving the signs and symptoms of the patients.
PubMed: 37557040
DOI: 10.1016/j.ijscr.2023.108618 -
Bioinformatics (Oxford, England) Oct 2023Precise identification of cancer cells in patient samples is essential for accurate diagnosis and clinical monitoring but has been a significant challenge in machine...
MOTIVATION
Precise identification of cancer cells in patient samples is essential for accurate diagnosis and clinical monitoring but has been a significant challenge in machine learning approaches for cancer precision medicine. In most scenarios, training data are only available with disease annotation at the subject or sample level. Traditional approaches separate the classification process into multiple steps that are optimized independently. Recent methods either focus on predicting sample-level diagnosis without identifying individual pathologic cells or are less effective for identifying heterogeneous cancer cell phenotypes.
RESULTS
We developed a generalized end-to-end differentiable model, the Cell Scoring Neural Network (CSNN), which takes sample-level training data and predicts the diagnosis of the testing samples and the identity of the diagnostic cells in the sample, simultaneously. The cell-level density differences between samples are linked to the sample diagnosis, which allows the probabilities of individual cells being diagnostic to be calculated using backpropagation. We applied CSNN to two independent clinical flow cytometry datasets for leukemia diagnosis. In both qualitative and quantitative assessments, CSNN outperformed preexisting neural network modeling approaches for both cancer diagnosis and cell-level classification. Post hoc decision trees and 2D dot plots were generated for interpretation of the identified cancer cells, showing that the identified cell phenotypes match the cancer endotypes observed clinically in patient cohorts. Independent data clustering analysis confirmed the identified cancer cell populations.
AVAILABILITY AND IMPLEMENTATION
The source code of CSNN and datasets used in the experiments are publicly available on GitHub (http://github.com/erobl/csnn). Raw FCS files can be downloaded from FlowRepository (ID: FR-FCM-Z6YK).
Topics: Humans; Neural Networks, Computer; Neoplasms; Flow Cytometry; Software; Hematologic Neoplasms
PubMed: 37756695
DOI: 10.1093/bioinformatics/btad585 -
BioRxiv : the Preprint Server For... Nov 2023Persistent and uncontrolled SARS-CoV-2 replication in immunocompromised individuals has been observed and may be a contributing source of novel viral variants that...
Persistent and uncontrolled SARS-CoV-2 replication in immunocompromised individuals has been observed and may be a contributing source of novel viral variants that continue to drive the pandemic. Importantly, the effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. Here we conducted a pilot study wherein two pigtail macaques (PTM) chronically infected with SIVmac239 were exposed to SARS-CoV-2 and monitored for six weeks for clinical disease, viral replication, and viral evolution, and compared to our previously published cohort of SIV-naïve PTM infected with SARS-CoV-2. At the time of SARS-CoV-2 infection, one PTM had minimal to no detectable CD4+ T cells in gut, blood, or bronchoalveolar lavage (BAL), while the other PTM harbored a small population of CD4+ T cells in all compartments. Clinical signs were not observed in either PTM; however, the more immunocompromised PTM exhibited a progressive increase in pulmonary infiltrating monocytes throughout SARS-CoV-2 infection. Single-cell RNA sequencing (scRNAseq) of the infiltrating monocytes revealed a less activated/inert phenotype. Neither SIV-infected PTM mounted detectable anti-SARS-CoV-2 T cell responses in blood or BAL, nor anti-SARS-CoV-2 neutralizing antibodies. Interestingly, despite the diminished cellular and humoral immune responses, SARS-CoV-2 viral kinetics and evolution were indistinguishable from SIV-naïve PTM in all sampled mucosal sites (nasal, oral, and rectal), with clearance of virus by 3-4 weeks post infection. SIV-induced immunodeficiency significantly impacted immune responses to SARS-CoV-2 but did not alter disease progression, viral kinetics or evolution in the PTM model. SIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants.
PubMed: 38014096
DOI: 10.1101/2023.11.15.567132