Sagittal Balance Parameters and Proximal Junctional Kyphosis in Adolescent Idiopathic Scoliosis.

Background: To review and evaluate multiple preoperative and postoperative sagittal parameters and their association with the risk of developing proximal junctional kyphosis (PJK) in patients with adolescent idiopathic scoliosis (AIS) who undergo correction surgery. Methods: A systematic search was performed in December 2022 in PubMed, Embase and the Cochrane Library to retrieve all the studies relevant to our research. After the study selection and data extraction following PRISMA guidelines, RevMan 5.3 was used for statistical analysis. All the analyzed factors were evaluated by using odds ratios and weighted mean differences with 95% confidence intervals. Moreover, the meta-analysis of proportions via MedCalc was used for analyzing quantitative data from the studies. Results: A total of 22 studies were included in our meta-analysis. All the available values of sagittal parameters were evaluated. Among all the potential risk factors, higher preoperative thoracic kyphosis (Test for overall effect Z = 11.79, p < 0.00001), higher preoperative sagittal vertical axis (SVA) (test for overall effect Z = 11.19, p < 0.00001), greater thoracic kyphosis change post-op. compared to pre-op. (test for overall effect Z = 6.02, p < 0.00001), increased postoperative lumbar lordosis (test for overall effect Z = 3.65, p = 0.0003), higher post-op. SVA (test for overall effect Z = 24.93, p < 0.00001) and a larger pelvic incidence/lumbar lordosis (PI/LL) mismatch (test for overall effect Z = 20.50, p < 0.00001) were found to be the risk factors for PJK after AIS surgery. Moreover, a decreased rod contour angle (RCA) (test for overall effect Z = 3.79, p < 0.0002) and higher proximal junctional angle-rod contour angle (PJA-RCA) (test for overall effect Z = 39.18, p < 0.00001) play a significant role in the risk of developing PJK after AIS correction. Conclusions: Sagittal balance is of great importance when considering the surgical correction of AIS. Many factors in our meta-analysis were found to increase the incidence for PJK such as higher preoperative thoracic kyphosis and pre-op. SVA. Furthermore, increased thoracic kyphosis change, increased post-operative lumbar lordosis, SVA and PI/LL mismatch are also factors that influence the possibility of post-op. PJK. Lastly, RCA and PJA-RCA are two important factors that need attention during AIS, as over-contouring of the rod could lead to PJK in AIS patients.

Correction: Characterisation of ATP-Dependent Mur Ligases Involved in the Biogenesis of Cell Wall Peptidoglycan in Mycobacterium tuberculosis.

[This corrects the article DOI: 10.1371/journal.pone.0060143.].

Incidence of vertebral artery injury in patients undergoing cervical spine trauma surgery in correlation with surgical approach: A review.

Spinal cord injuries at the cervical spine level represent the most consequential of the related injuries at all levels of the spine. They can trigger permanent unilateral or bilateral damage with conspicuous disability. Regarding unstable injuries, the gold standard approach is open reduction and osteosynthesis, which can select between anterior and posterior surgical access. Each of the aforementioned approaches demonstrates both advantages and disadvantages; thus, it is up to the surgeon to determine the optimal option concerning the patient's safety. Diligent intraoperative control of anatomical reduction is pivotal to obtaining the best feasible postoperative outcomes. Literature data delineate copious complications following surgical intervention in the cervical spine. Indubitably, the most crucial intraoperative complication accounts for vascular injuries, with the most preponderant being the corrosion of the vertebral artery, as it is potentially life-threatening. This paper aims to provide a succinct and compendious review of the existing literature regarding cervical spinal cord injuries and to deduce many inferences concerning the incidence of iatrogenic vertebral artery injuries in relation to the surgical approach for fracture reduction.

Rehabilitation Prognostic Factors following Hip Fractures Associated with Patient's Pre-Fracture Mobility and Functional Ability: A Prospective Observation Study.

Low physical function is associated with poor outcomes in the elderly population suffering from hip fractures. The present study aims to evaluate the prognostic tools for predicting patient recovery after hip fractures and investigate the correlation between the pre-fracture motor and functional statuses. A prospective study was performed, including 80 patients suffering from hip fractures. Patient history, previous falls, the type of fracture and overall survival were evaluated. Patient-reported outcome measures (SF-36, EQ-5D/VAS, Charlson Comorbidity Index (CCI), Short Physical Performance Battery (SPPB), Timed Up and Go (TUG) and Harris Hip Score (HHS)) were monitored before hospital discharge at 6 weeks, and 3, 6 and 12 months postoperatively. Overall, 55% of patients experienced at least one fall, and 46% of them used crutches before the fracture. The average CCI score was 6.9. The SPPB score improved from 1.4 ± 1.3 (1 week) to 4.4 ± 2.1 (48 weeks). A one-year age increase, female sex, and prior history of falls lead to 0.1-, 0.92-, 0.56-fold lower SPPB scores, respectively, at 12 months. The HHS recorded the greatest improvement between 6 and 12 weeks (52.1 ± 14.6), whereas the TUG score continued to improve significantly from 139.1 ± 52.6 s (6 weeks) to 66.4 ± 54 s (48 weeks). The SPPB and performance test can be routinely used as a prognostic tool.

The Effect of Postoperative Physical Therapy Following Hip Fracture: A Literature Review.

Hip fractures in the elderly have become a major public health concern as the population ages. Post-operative rehabilitation is associated with improved outcomes and a greater likelihood of returning to pre-operative functional capacity. Several studies have been conducted to investigate various post-operative recovery pathways. However, little is known about which post-operative rehabilitation pathways for hip fractures are most effective in improving patient outcomes. No clear evidence-based guidelines for a standard mobilization protocol for patients are currently available. This review aims to investigate post-operative recovery pathways to help patients suffering from hip fracture return to pre-fracture condition and to quantify pre-operative and post-operative scores for objective rehabilitation evaluation. Measuring pre-operative activity and comparing it to post-operative follow-up values can help predict post-operative rehabilitation functional outcomes.

A Systematic Review of the Diagnosis and Treatment of Non-Typhoid Salmonella Spondylodiscitis in Immunocompetent Children.

The aim of this systematic review is to distinguish the clinical features of immunocompetent children with non-typhoid Salmonella spondylodiscitis and summarize the diagnosis, diagnostic tools, and treatment methods to guide clinicians. The review was conducted according to the preferred PRISMA guidelines. We conducted a literature search in the PubMed, Embase, and Cochrane Library databases. Article screening, data extraction, and study evaluation were performed by two independent reviewers. A total of 20 articles, published between 1977 and 2020, were selected, which included 21 patients with average age of 12.76 years (range, 2-18) without comorbidities; in total, 19% of the patients had positive blood cultures for non-typhoid Salmonella, and 80.9% underwent either CT-guided or open biopsy, which were positive for NTS. All infections were monomicrobial, and 11 different serotypes of non-typhoid Salmonella were identified. Analyzing the reviewed cases, 52.4% of the patients presented with fever, 90.5% had localized pain, and only 19% had gastroenteritis. The most common level of discitis was the lumbar region, especially the L4/L5 level. Primarily, third-generation cephalosporin was administered, and antibiotic treatment was given for an average of 9.6 weeks. Non-typhoid Salmonella spondylodiscitis is a rare clinical entity in healthy and immunocompetent children. The identification of the responsible organism is essential to guide antibiotic therapy and define the treatment duration. A significant limiting factor in this systematic review was the lack of published research articles and case series due to the rarity of the disease.

Dysphagia as a Postoperative Complication of Anterior Cervical Discectomy and Fusion.

Anterior cervical discectomy and fusion (ACDF), despite its possible complications, remains the gold standard for the surgical treatment of patients with radiculopathy and/or myelopathy caused by cervical intervertebral disc herniation or spondylosis. Despite its high rate of incidence, postoperative dysphagia following ACDF is still poorly understood; its pathogenesis remains relatively unknown, and its risk factors are still a subject of debate. The aim of this study is to review the incidence, pathogenesis, diagnosis, and methods of prevention of dysphagia in ACDF patients. To this end, a literature review was conducted based on the PubMed internet database. Article titles were searched by using the following keywords: "dysphagia" and "anterior cervical discectomy and fusion" or "ACDF". The search was limited to prospective clinical studies evaluating dysphagia after ACDF surgery. Studies published in non-English languages, retrospective studies, cadaveric studies, reviews, case reports, study protocols, and commentary studies were excluded. Initially, 335 studies were identified after a primary search. After the application of the exclusion criteria, 73 studies remained for the final analysis. This literature review focused on identifying the rate of dysphagia and the various risk factors leading to this complication by comparing and evaluating the current literature with a wide spectrum of heterogeneity concerning patients, surgeons, and surgical techniques. A mean dysphagia rate of 19.4% (95% CI: 9.6%-29.1%) based on the findings of the included studies correlating dysphagia directly with ACDF procedures was calculated. Various established risk factors leading to dysphagia include the female sex, smoking, the surgical approach, rhBMP-2 use, and multilevel surgery, while zero-profile devices seem to reduce dysphagia risk. The diagnosis is based on clinical and radiological findings, especially prevertebral soft-tissue swelling. However, videofluoroscopic and endoscopic studies have been recently used for the evaluation of dysphagia. The role of local administration of steroids in the prevention of dysphagia has not yet been clarified. This review underscores the prevailing rudimentary understanding of the problem of dysphagia after ACDF procedures and highlights the need for more sensitive, factor-specific studies for understanding the impact of various risk factors on the incidence rate of dysphagia.

Angiogenesis in Spinal Cord Injury: Progress and Treatment.

Traumatic spinal cord injury (SCI) provokes the onset of an intricate pathological process. Initial primary injury ruptures local micro-neuro-vascularcomplex triggering the commencement of multi-factorial secondary sequences which exert significant influence on neurological deterioration progress. Stimulating by local ischemia, neovascularization pathways emerge to provide neuroprotection and improve functional recovery. Although angiogenetic processes are prompted, newly formed vascular system is frequently inadequate to distribute sufficient blood supply and improve axonal recovery. Several treatment interventions have been endeavored to achieve the optimal conditions in SCI microenvironment, enhancing angiogenesis and improve functional recovery. In this study we review the revascularization pathogenesis and importance within the secondary processes and condense the proangiogenic influence of several angiogenetic-targeted treatment interventions.

Application of Collagen-Based Scaffolds for the Treatment of Spinal Cord Injuries in Animal Models: A Literature Update.

SCI is regarded as one of the most devastating central nervous system (CNS) injuries, exhibiting an alarmingly rising incidence rate, indirectly connected with the expansion of the global economy. The consequences of SCI are multidimensional: SCI injuries may result in permanent voluntary motor dysfunction and loss of sensation while incurring heavy economic and psychological burdens as part of the treatment. Thus, it is crucial to develop effective and suitable SCI treatment strategies. Collagen-based scaffold application is one of the most promising methods of SCI treatment. This review compiles newer bibliographical data regarding the application of collagen scaffolds for the treatment of Spinal cord injury (SCI) in animal models. Recently, several relevant studies have been carried out using carefully selected animals with similar pathophysiology to humans. In mouse, rat and canine models that have undergone transection or hemisection, the stump connection, the transplanted cell differentiation, and the elimination of glial scar are promising. Also, encouraging results have been found regarding the increased neuronal growth, the decreased collagen deposition, the behavioral recovery, the improved electrophysiology, and the enhanced axonal regeneration.

Stem Cell Therapy for Spinal Cord Injury: A Review of Recent Clinical Trials.

Spinal cord injury (SCI) remains an incurable, life-changing neurological condition, causing permanent loss of motor and sensory function in millions of people worldwide and affecting them in every aspect of their personal and social life. In the last two decades, after its success in various fields of medicine, stem cell therapy has been investigated in the research field as a potential treatment for SCI. This review focuses on the pathophysiology of SCI, the characteristics of the different stem cell therapies used for its treatment, and the results of these therapies in recently published clinical trials.

Pre-Clinical Tools for Predicting Drug Efficacy in Treatment of Tuberculosis.

Combination therapy has, to some extent, been successful in limiting the emergence of drug-resistant tuberculosis. Drug combinations achieve this advantage by simultaneously acting on different targets and metabolic pathways. Additionally, drug combination therapies are shown to shorten the duration of therapy for tuberculosis. As new drugs are being developed, to overcome the challenge of finding new and effective drug combinations, systems biology commonly uses approaches that analyse mycobacterial cellular processes. These approaches identify the regulatory networks, metabolic pathways, and signaling programs associated with M. tuberculosis infection and survival. Different preclinical models that assess anti-tuberculosis drug activity are available, but the combination of models that is most predictive of clinical treatment efficacy remains unclear. In this structured literature review, we appraise the options to accelerate the TB drug development pipeline through the evaluation of preclinical testing assays of drug combinations.

The Role of Sclerostin in Bone Diseases.

Sclerostin has been identified as an important regulator of bone homeostasis through inhibition of the canonical Wnt-signaling pathway, and it is involved in the pathogenesis of many different skeletal diseases. Many studies have been published in the last few years regarding sclerostin's origin, regulation, and mechanism of action. The ongoing research emphasizes the potential therapeutic implications of sclerostin in many pathological conditions with or without skeletal involvement. Antisclerostin antibodies have recently been approved for the treatment of osteoporosis, and several animal studies and clinical trials are currently under way to evaluate the effectiveness of antisclerostin antibodies in the treatment of other than osteoporosis skeletal disorders and cancer with promising results. Understanding the exact role of sclerostin may lead to new therapeutic approaches for the treatment of skeletal disorders.

Culture-Free Enumeration of Mycobacterium tuberculosis in Mouse Tissues Using the Molecular Bacterial Load Assay for Preclinical Drug Development.

BACKGROUND: The turnaround times for phenotypic tests used to monitor the bacterial load of Mycobacterium tuberculosis, in both clinical and preclinical studies, are delayed by the organism's slow growth in culture media. The existence of differentially culturable populations of M.tuberculosis may result in an underestimate of the true number. Moreover, culture methods are susceptible to contamination resulting in loss of critical data points. OBJECTIVES: We report the adaptation of our robust, culture-free assay utilising 16S ribosomal RNA, developed for sputum, to enumerate the number of bacteria present in animal tissues as a tool to improve the read-outs in preclinical drug efficacy studies. METHODS: Initial assay adaptation was performed using naïve mouse lungs spiked with known quantities of M. tuberculosis and an internal RNA control. Tissues were homogenised, total RNA extracted, and enumeration performed using RT-qPCR. We then evaluated the utility of the assay, in comparison to bacterial counts estimated using growth assays on solid and liquid media, to accurately inform bacterial load in tissues from M. tuberculosis-infected mice before and during treatment with a panel of drug combinations. RESULTS: When tested on lung tissues derived from infected mice, the MBL assay produced comparable results to the bacterial counts in solid culture (colony forming units: CFU). Notably, under specific drug treatments, the MBL assay was able to detect a significantly higher number of M. tuberculosis compared to CFU, likely indicating the presence of bacteria that were unable to produce colonies in solid-based culture. Additionally, growth recovery in liquid media using the most probable number (MPN) assay was able to account for the discrepancy between the MBL assay and CFU number, suggesting that the MBL assay detects differentially culturable sub-populations of M. tuberculosis. CONCLUSIONS: The MBL assay can enumerate the bacterial load in animal tissues in real time without the need to wait for extended periods for cultures to grow. The readout correlates well with CFUs. Importantly, we have shown that the MBL is able to measure specific populations of bacteria not cultured on solid agar. The adaptation of this assay for preclinical studies has the potential to decrease the readout time of data acquisition from animal experiments and could represent a valuable tool for tuberculosis drug discovery and development.

A new strategy for hit generation: Novel in cellulo active inhibitors of CYP121A1 from Mycobacterium tuberculosis via a combined X-ray crystallographic and phenotypic screening approach (XP screen).

There is a pressing need for new drugs against tuberculosis (TB) to combat the growing resistance to current antituberculars. Herein a novel strategy is described for hit generation against promising TB targets involving X-ray crystallographic screening in combination with phenotypic screening. This combined approach (XP Screen) affords both a validation of target engagement as well as determination of in cellulo activity. The utility of this method is illustrated by way of an XP Screen against CYP121A1, a cytochrome P450 enzyme from Mycobacterium tuberculosis (Mtb) championed as a validated drug discovery target. A focused screening set was synthesized and tested by such means, with several members of the set showing promising activity against Mtb strain H37Rv. One compound was observed as an X-ray hit against CYP121A1 and showed improved activity against Mtb strain H37Rv under multiple assay conditions (pan-assay activity). Data obtained during X-ray crystallographic screening were utilized in a structure-based campaign to design a limited number of analogues (less than twenty), many of which also showed pan-assay activity against Mtb strain H37Rv. These included the benzo[b][1,4]oxazine derivative (MIC90 6.25 µM), a novel hit compound suitable as a starting point for a more involved hit to lead candidate medicinal chemistry campaign.

Sclerostin and Its Involvement in the Pathogenesis of Idiopathic Scoliosis.

Idiopathic scoliosis is a disorder of unknown etiology. Bone biopsies from idiopathic scoliosis patients revealed changes at cellular and molecular level. Osteocytic sclerostin is downregulated, and serum level of sclerostin is decreased. Osteocytes in idiopathic scoliosis appear to be less active with abnormal canaliculi network. Differentiation of osteoblasts to osteocytes is decelerated, while Wnt/ß-catenin signaling pathway is overactivated and affects normal bone mineralization that leads to inferior mechanical properties of the bone, which becomes susceptible to asymmetrical forces and causes deformity of the spinal column. Targeting bone metabolism during growth by stimulating sclerostin secretion from osteocytes and restoring normal function of Wnt/ß-catenin signaling pathway could, in theory, increase bone strength and prevent deterioration of the scoliotic deformity.

Methylprednisolone stimulated gene expression (GILZ, MCL-1) and basal cortisol levels in multiple sclerosis patients in relapse are associated with clinical response.

Glucocorticoids (GCs) are the main treatment of relapse in multiple sclerosis (MS). Decreased sensitivity to GCs in MS patients has been associated with lack of the suppressive effect of GCs on inflammatory molecules as well as increased resistance to apoptosis. We investigated GC-sensitivity by measuring the effect of intravenous methylprednisolone (IVMP) treatment on transactivation of anti-inflammatory and apoptotic genes (GILZ, MCL-1 and NOXA respectively), in accordance to clinical outcome. Thirty nine MS patients were studied: 15 with clinically isolated syndrome (CIS), 12 with relapsing remitting (RRMS) and 12 with secondary progressive (SPMS) under relapse. Patients underwent treatment with IVMP for 5 days. Blood was drawn before IVMP treatment on day 1 and 1 h after IVMP treatment on days 1 and 5. GIlZ, MCL-1 and NOXA were determined by qPCR. The Expanded Disability Status was evaluated and patients were divided according to their clinical response to IVMP. GILZ and MCL-1 gene expression were significantly higher following first IVMP treatment in responders, compared to non-responders. Furthermore, serum basal cortisol and 1,25-OH Vitamin D levels were significantly higher in clinical-responders as compared to non-clinical responders. Our findings suggest that the differential GILZ and MCL-1 gene expression between clinical-responders and non-clinical responders may implicate the importance of GILZ and MCL-1 as possible markers for predicting glucocorticoid sensitivity and response to GC-therapy in MS patients following first IVMP injection.

One Year Later: What Was the Impact of the COVID-19 Pandemic on Orthopedic Practice?

The coronavirus disease 2019 (COVID-19) pandemic is an enormous challenge for health care systems worldwide. Although it is widely accepted that orthopedic service has been reduced during the COVID-19 pandemic, little is known about the magnitude and qualitative characteristics of this reduction. The aim of the present study is to quantify the impact of the COVID-19 pandemic on everyday orthopedic practice and to detect the qualitative details of this impact in order to provide data for appropriate planning of health care policy. Data from the year 2020, when the COVID-19 pandemic occurred, regarding the number of patients examined in the emergency department, outpatient clinics, as well as the number of hospital admissions, were recorded for each month. The number of surgical procedures per month was also recorded and evaluated in relation to the category and the anatomical region that these procedures pertained to. Similar data from the year 2019 were used as a control group. The mean number of patients who visited the emergency department, the outpatient clinics, and those who were admitted to the hospital per month decreased by 47.2%, 30.4%, and 9%, respectively. Overall, the mean number of orthopedic operations decreased by 11.7%, with trauma operations being reduced by 8.9% and elective operations by 13% per month. Based on the findings of the present study, the impact of the COVID-19 pandemic on orthopedic patients is definitely negative. The establishment of new guidelines and re-distribution of resources is required to return to a normal function of orthopedic practice within hospitals.

Orthopedic Implant-Related Biofilm Pathophysiology: A Review of the Literature.

Orthopedic implant-related infections remain a major problem even nowadays. Bacterial resistance through biofilm formation, in addition to the limited treatment options available, has resulted in an increased effort to better understand pathophysiology mechanisms. We performed a review of the literature in order to identify major biofilm formation pathways through which possible treatment strategies could arise.

New Strategies in Neurogenic Heterotopic Ossification.

The term neurogenic heterotopic ossification (NHO) is used to describe the pathological bone formation in soft tissues, due to spinal cord or brain injury. Commonly is presented with pain and stiffness of the affected joint. NHO affects the quality of life of these patients, delays their rehabilitation and therefore increases morbidity. The aim of this article is to emphasize pathophysiology mechanism and review new molecular treatments of heterotopic ossification (HO). It was demonstrated that potent treatment strategies are based on understanding the molecular mechanisms and aiming to inhibit the pathological process of the HO in various stages. New treatments are targeting several factors such as bone morphogenetic proteins (BMPs), retinoic acid receptors (RARs), hypoxic inhibitors (Hif1-inhibitors, rapamycin), free radical scavengers and immunological agents (imatinib). The endogenous pathways that lead to HO at molecular and cellular levels have been the aim of many studies in recent years. New treatment options for HO should be recommended due to the ineffectiveness of traditional older options, such as anti-inflammatory drugs and radiation, especially in the case of NHO.