Efficacy of perioperative gabapentin use in patients with idiopathic scoliosis undergoing fusion surgery: a systematic review and meta-analysis.

PURPOSE: This study aimed to assess whether the perioperative use of gabapentin was associated with decreased opioid use. METHODS: A meta-analysis was performed using PubMed, Embase, Scopus, and Cochrane Library. The randomized clinical trials included were focused on patients with adolescent idiopathic scoliosis who underwent posterior fusion surgery and were treated with gabapentin versus placebo medicine. The primary outcomes were opioid consumption at 24, 48, 72, and 96 h; time to introduction of oral medication, length of hospital stay, and period of urinary catheterization were also recorded. Data were combined using the Review Manager 5.4 software. RESULTS: Four randomized clinical trials with a pool of 196 adolescent patients (mean age: 14.8 ± 2.0 years) were included. At 24 and 48 h after surgery, opioid consumption was significantly lower in the gabapentin group: (standardized mean difference [SMD]: -0.50; 95% confidence interval [CI] - 0.79 to - 0.22) and (SMD: - 0.59; 95% CI - 0.88 to - 0.30), respectively. At 72 and 96 h, there were no significant differences between studies: (SMD: - 0.19; 95% CI - 0.52 to 0.13) and (SMD: 0.12; 95% CI - 0.25 to 0.50), respectively. Regarding the administration type, there were significant differences in favor of the 15 mg/kg subgroup with 600 mg at 48 h (SMD: - 0.69; 95% CI - 1.08 to - 0.30). There were no significant differences concerning the time to introduction of oral medication (MD: - 0.08; 95% CI - 0.39 to 0.23), hospitalization time (MD: - 0.12; 95% CI - 0.40 to 0.16), or period of urinary catheterization (SMD: - 0.27; 95% CI - 0.58 to 0.05). CONCLUSIONS: Gabapentin decreased opioid consumption during the first 48 h. Doses of 15 mg/kg showed superiority in reducing opioid consumption in the first 48 h. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Meta-analysis on the efficacy and safety of anterior vertebral body tethering in adolescent idiopathic scoliosis.

PURPOSE: In this meta-analysis, we analyzed the efficacy and safety of anterior vertebral body tethering in patients with adolescent idiopathic scoliosis. METHODS: We performed a literature search and analyzed the following data: baseline characteristics, efficacy measures (corrections of the main thoracic curve, proximal thoracic curve, and thoracolumbar curve, thoracic kyphosis, lumbosacral lordosis, rib hump, lumbar prominence and SRS-22 scores, and complications. Analyses were performed with Cochrane's Review Manager version 5.4. RESULTS: Twelve studies met the inclusion criteria. Significant corrections of the main thoracic (MD 22.51, 95% CI 12.93 to 32.09) proximal thoracic (MD 10.14°, 95% CI 7.25° to 13.02°), and thoracolumbar curve (MD 12.16, 95% CI 9.14 to 15.18) were found. No statistically significant corrections were observed on the sagittal plane assessed by thoracic kyphosis (MD - 0.60°, 95% CI - 2.45 to 1.26; participants = 622; studies = 4; I2 = 36%) and lumbosacral lordosis (MD 0.19°, 95% CI - 2.16° to 2.54°). Significant corrections were identified for rib hump (MD 5.26°, 95% CI 4.19° to 6.32°) and lumbar prominence (MD 1.20°, 95% CI 0.27° to 2.13°) at final follow-up. Significant improvements of total SRS-22 score (MD - 0.96, 95% CI - 1.10 to - 0.83) were achieved at final follow-up. The most common complication was overcorrection (8.0%) and tether breakage (5.9%), with a reoperation rate of 10.1%. CONCLUSIONS: Anterior vertebral body tethering is effective to reduce the curve in the coronal plane and clinical deformity. Maximum correction is achieved at one year. The method should, however, be optimized to reduce the rate of complications.

Identification of circulating miRNAs differentially expressed in patients with Limb-girdle, Duchenne or facioscapulohumeral muscular dystrophies.

BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a rare neuromuscular disease including a growing and heterogeneous number of subtypes with variable phenotype. Their clinical and histopathological characteristics frequently overlap with other neuromuscular dystrophies. Our goal was to identify, by a non-invasive method, a molecular signature including biochemical and epigenetic parameters with potential value for patient prognosis and stratification. RESULTS: Circulating miRNome was obtained by smallRNA-seq in plasma from LGMD patients (n = 6) and matched-controls (n = 6). Data, validated by qPCR in LGMD samples, were also examined in other common muscular dystrophies: Duchenne (DMD) (n = 5) and facioscapulohumeral muscular dystrophy (FSHD) (n = 4). Additionally, biochemical and clinical parameters were analyzed. miRNome analysis showed that thirteen differentially expressed miRs could separate LGMD vs control group by hierarchical clustering. Most of differentially expressed miRs in LGMD patients were up-regulated (miR-122-5p, miR-122b-3p, miR-6511a-3p, miR-192-5p, miR-574-3p, mir-885-3p, miR-29a-3p, miR-4646-3p, miR-203a-3p and miR-203b-5p) whilst only three of sequenced miRs were significantly down-regulated (miR-19b-3p, miR-7706, miR-323b-3p) when compared to matched controls. Bioinformatic analysis of target genes revealed cell cycle, muscle tissue development, regeneration and senescence as the most affected pathways. Four of these circulating miRs (miR-122-5p, miR-192-5p, miR-19b-3p and miR-323b-3p), together with the myomiR miR-206, were further analysed by qPCR in LGMD, DMD and FSHD. The receiver operating characteristic curves (ROC) revealed high area under the curve (AUC) values for selected miRs in all groups, indicating that these miRs have good sensitivity and specificity to distinguish LGMD, DMD and FSHD patients from healthy controls. miR-122-5p, miR-192-5p and miR-323-3p were differentially expressed compared to matched-controls in all groups but apparently, each type of muscular dystrophy showed a specific pattern of miR expression. Finally, a strong correlation between miRs and biochemical data was only found in LGMD patients: while miR-192-5p and miR-122-5p negatively correlated with CK, miR-192-5p positively correlated with vitamin D3 and ALP. CONCLUSIONS: Although limited by the small number of patients included in this study, we propose here a specific combination of circulating miR-122-5p/miR-192-5p/miR-323-3 and biochemical parameters as a potential molecular signature whose clinical value for LGMD patient prognosis and stratification should be further confirmed in a larger cohort of patients.

Meta-analysis of the efficacy of ketamine in postoperative pain control in adolescent idiopathic scoliosis patients undergoing spinal fusion.

PURPOSE: In this meta-analysis, we aim to compare ketamine use versus a control group (saline solution) during induction of anesthesia in adolescent idiopathic scoliosis patients undergoing fusion surgery in terms of postoperative opioid consumption, pain control, and side effects. METHODS: A PubMed search of studies published over the last 20 years using the descriptor/terms "ketamine AND scoliosis" was performed. Baseline characteristics of each article were obtained and efficacy measures analyzed (morphine equivalent treatment at 24, 48, and 72 h postoperatively, complications (vomiting/nausea and pruritus), length of hospital stay (days); and pain score (VAS)) (Review Manager 5.4 software package). RESULTS: Five randomized clinical trials were included. Morphine administration showed statistically significant differences at 24 and 48 h (MD - 0.15, 95% CI - 0.18 to - 0.12) and (MD - 0.26, 95% CI - 0.31 to - 0.21) between the ketamine and control (saline solution), respectively. No intergroup differences were found regarding nausea/vomiting and pruritus (OR 0.77, 95% CI 0.35 to 1.67) and (OR 0.71, 95% CI 0.31 to 1.62), respectively, same as for the pain score (MD - 0.75, 95% CI - 1.71 to 0.20). CONCLUSIONS: The use intraoperative and postoperative continuous low doses of ketamine significantly reduces opioid use throughout the first 48 h in patients with AIS who undergo posterior spinal fusion.

From genetics to epigenetics to unravel the etiology of adolescent idiopathic scoliosis.

Scoliosis is defined as the three-dimensional (3D) structural deformity of the spine with a radiological lateral Cobb angle (a measure of spinal curvature) of ≥10° that can be caused by congenital, developmental or degenerative problems. However, those cases whose etiology is still unknown, and affect healthy children and adolescents during growth, are the commonest form of spinal deformity, known as adolescent idiopathic scoliosis (AIS). In AIS management, early diagnosis and the accurate prediction of curve progression are most important because they can decrease negative long-term effects of AIS treatment, such as unnecessary bracing, frequent exposure to radiation, as well as saving the high costs of AIS treatment. Despite efforts made to identify a method or technique capable of predicting AIS progression, this challenge still remains unresolved. Genetics and epigenetics, and the application of machine learning and artificial intelligence technologies, open up new avenues to not only clarify AIS etiology, but to also identify potential biomarkers that can substantially improve the clinical management of these patients. This review presents the most relevant biomarkers to help explain the etiopathogenesis of AIS and provide new potential biomarkers to be validated in large clinical trials so they can be finally implemented into clinical settings.

Extracellular Proteins: Novel Key Components of Metal Resistance in Cyanobacteria?

Metals are essential for all living organisms and required for fundamental biochemical processes. However, when in excess, metals can turn into highly-toxic agents able to disrupt cell membranes, alter enzymatic activities, and damage DNA. Metal concentrations are therefore tightly controlled inside cells, particularly in cyanobacteria. Cyanobacteria are ecologically relevant prokaryotes that perform oxygenic photosynthesis and can be found in many different marine and freshwater ecosystems, including environments contaminated with heavy metals. As their photosynthetic machinery imposes high demands for metals, homeostasis of these micronutrients has been widely studied in cyanobacteria. So far, most studies have focused on how cells are capable of controlling their internal metal pools, with a strong bias toward the analysis of intracellular processes. Ultrastructure, modulation of physiology, dynamic changes in transcription and protein levels have been studied, but what takes place in the extracellular environment when cells are exposed to an unbalanced metal availability remains largely unknown. The interest in studying the subset of proteins present in the extracellular space has only recently begun and the identification and functional analysis of the cyanobacterial exoproteomes are just emerging. Remarkably, metal-related proteins such as the copper-chaperone CopM or the iron-binding protein FutA2 have already been identified outside the cell. With this perspective, we aim to raise the awareness that metal-resistance mechanisms are not yet fully known and hope to motivate future studies assessing the role of extracellular proteins on bacterial metal homeostasis, with a special focus on cyanobacteria.