Off-Target Inhibition of Human Dihydroorotate Dehydrogenase (DHODH) Highlights Challenges in the Development of Fat Mass and Obesity-Associated Protein (FTO) Inhibitors.

FTO, an -methyladenosine (mA) and ,2'--dimethyladenosine (mA) RNA demethylase, is a promising target for treating acute myeloid leukemia (AML) due to the significant anticancer activity of its inhibitors in preclinical models. Here, we demonstrate that the FTO inhibitor FB23-2 suppresses proliferation across both AML and CML cell lines, irrespective of FTO dependency, indicating an alternative mechanism of action. Metabolomic analysis revealed that FB23-2 induces the accumulation of dihydroorotate (DHO), a key intermediate in pyrimidine nucleotide synthesis catalyzed by human dihydroorotate dehydrogenase (DHODH).

Clinical and Radiographic Results in Thoracic Hyperkyphosis Surgical Treatment Considering the Optimal Distal Fusion Area.

The aim of this retrospective study was to evaluate the clinical and radiographic outcomes of patients who underwent posterior correction and fusion for thoracic hyperkyphosis, with a focus on determining the optimal distal fusion level. From 2006 to 2012, 26 patients with a median age of 16.8 years (range 14-25), diagnosed with either idiopathic hyperkyphosis or Scheuermann's kyphosis, underwent posterior fusion and Ponte osteotomies at two medical centers.

Radiological evaluation of fusion patterns after Lateral Lumbar Interbody fusion with 3D-printed porous titanium cages vs. conventional titanium cages.

Introduction: The assessment of segmental fusion after Lateral Lumbar Interbody fusion (LLIF) using 3D-printed porous titanium cage is still not well studied. Various criteria, such as the presence of bone bridges (BB) between adjacent vertebrae, serve as indicators for anterior fusion. However, limited radiological studies have investigated zygapophyseal joints (ZJ) status following LLIF with porous titanium cages vs.

Sex Differences in Patient-rated Outcomes After Lumbar Spinal Fusion for Degenerative Disease: A Multicenter Cohort Study.

Study Design: Heterogeneous data collection via a mix of prospective, retrospective, and ambispective methods.

Objective: To evaluate the effect of biological sex on patient-reported outcomes after spinal fusion surgery for lumbar degenerative disease.

Summary Of Background Data: Current literature suggests sex differences regarding clinical outcome after spine surgery may exist.

Posterior Cruciate Buckling Angle Variations Are Associated with Different Patterns of Medial Meniscus Tears in Anterior-Cruciate-Deficient Knees: Results of a Prospective Comparative Magnetic Imaging Resonance Study.

Background: The diagnosis of anterior cruciate ligament (ACL) tear relies on clinical evaluation and magnetic resonance imaging (MRI). Direct and indirect signs of ACL tear have been described with MRI evaluation. Posterior cruciate ligament (PCL) buckling has been described as an indirect radiographic sign of an ACL tear.

Multicenter external validation of prediction models for clinical outcomes after spinal fusion for lumbar degenerative disease.

Background: Clinical prediction models (CPM), such as the SCOAP-CERTAIN tool, can be utilized to enhance decision-making for lumbar spinal fusion surgery by providing quantitative estimates of outcomes, aiding surgeons in assessing potential benefits and risks for each individual patient. External validation is crucial in CPM to assess generalizability beyond the initial dataset. This ensures performance in diverse populations, reliability and real-world applicability of the results.

Differential regulation of mitochondrial uncoupling protein 2 in cancer cells.

The persistent growth of cancer cells is underscored by complex metabolic reprogramming, with mitochondria playing a key role in the transition to aerobic glycolysis and representing new therapeutic targets. Mitochondrial uncoupling protein 2 (UCP2) has attracted interest because of its abundance in rapidly proliferating cells, including cancer cells, and its involvement in cellular metabolism. However, the specific contributions of UCP2 to cancer biology remain poorly defined.

Rethinking Strategies for Multi-Metastatic Patients: A Comprehensive Retrospective Analysis on Open Posterior Fusion Versus Percutaneous Osteosynthesis in the Treatment of Vertebral Metastases.

Managing vertebral metastases (VM) is still challenging in oncology, necessitating the use of effective surgical strategies to preserve patient quality of life (QoL). Traditional open posterior fusion (OPF) and percutaneous osteosynthesis (PO) are well-documented approaches, but their comparative efficacy remains debated. This retrospective study compared short-term outcomes (6-12 months) between OPF and PO in 78 cancer patients with spinal metastases.

Critical Shoulder Angle in Patients With Cuff Tears.

Objective: The pathogenesis of rotator cuff tears (RCTs) is multifactorial. Critical shoulder angle (CSA), which represents the lateral extension of the acromion over the cuff, has been proposed as an extrinsic risk factor. The aim of the present systematic review and meta-analysis was to analyze the available literature regarding the correlation between RCT and CSA.

The Incidence of Screw Failure in Fenestrated Polyaxial Pedicle Screws vs. Conventional Pedicle Screws in the Treatment of Adolescent Idiopathic Scoliosis (AIS).

: Adolescent idiopathic scoliosis (AIS) is a spinal pathology affecting 0.47-5.2% of the population, often requiring surgical intervention to control deformity progression.

Trisomy 22 Mosaicism from Prenatal to Postnatal Findings: A Case Series and Systematic Review of the Literature.

Background: Among aneuploidies compatible with life, trisomy 22 mosaicism is extremely rare, and only about 25 postnatal and 18 prenatal cases have been described in the literature so far. The condition is mainly characterized by facial and body asymmetry, cardiac heart defects, facial dysmorphisms, growth failure, delayed puberty, and variable degrees of neurodevelopmental delay.

Problem: The scattered information regarding the condition and the dearth of data on its natural history and developmental outcomes restrict genetic counseling, particularly in prenatal settings.

Short-segment percutaneous fusion versus open posterior fusion with screw in the fractured vertebra for thoracolumbar junction burst vertebral fracture treatment.

Objectives: The treatment options for thoracolumbar junction burst fractures remain a topic of controversy. Short-segment percutaneous fixation (SSPF) and short-segment open fixation including the fractured level (SSOFIFL) are both viable procedures for managing these fractures. At present, there is a lack of evidence in the literature demonstrating the absolute superiority of one treatment over the other.

Extreme Lateral Interbody Fusion (XLIF) with Lateral Modular Plate Fixation: Preliminary Report on Clinical and Radiological Outcomes.

The lateral transpsoas approach (extreme lateral interbody fusion, or XLIF) allows surgeons to use various lordotic cage sizes to help restore intervertebral disk height, correct sagittal alignment, and improve fusion rates. The use of standalone devices has consistently raised doubts due to the high risk of complications and inadequate functional recovery that a circumferential arthrodesis can support. The recent introduction of a novel XLIF cage with adapted lateral plate fixation (XLPF) may further enhance the structural rigidity, consolidating the cage and plate into a singular modular entity.

Long-Term Clinical and Radiographic Outcomes After Bryan Cervical Disk Arthroplasty: A Systematic Literature Review.

Introductionː Cervical disk arthroplasty is a potential alternative procedure to anterior cervical decompression and fusion for the treatment of cervical disk disease. The aim of the study was to perform a systematic literature review on long-term clinical and radiological outcomes after Bryan cervical disk arthroplasty.Material and Methodsː A systematic literature review was performed according to PRISMA guidelines via PubMed and Embase, Scopus, and the Cochrane Library database by using the following keywords: "Bryan prosthesis"; "cervical disk arthroplasty"; "outcomes"; and "long-term follow-up.

Vertebral Candidiasis, the State of the Art: A Systematic Literature Review.

Objective: In recent years, Candida spondylodiscitis has represented an increasingly emerging disease in clinical practice. This condition requires long-term antibiotic therapy and sometimes surgical treatments. The main purpose of this study is to investigate the epidemiology, clinical and radiological aspects, treatment protocols, and outcomes of Candida-mediated vertebral osteomyelitis.

Are anxious and mixed depression two sides of the same coin? Similarities and differences in patients with bipolar I, II and unipolar disorders.

Background: Diagnostic criteria are not always useful to discriminate major depression with anxious distress (ADS-D; Diagnostic and Statistical Manual for Mental Disorders, version-5 [DSM-5] criteria) from mixed depression (Koukopoulos' criteria; KMX-D). So, clinicians need alternative tools to improve their diagnostic ability and to choose the most appropriate treatment. The aim of the present study is to identify socio-demographic and clinical features that discriminate patients with ADS-D from those with KMX-D.

Positioning accuracy and facet joints violation after percutaneous pedicle screws placement with robot-assisted versus fluoroscopy-guided technique: Systematic review and meta-analysis.

Introduction: Minimally invasive spine surgery became the gold standard for the treatment of many spinal diseases. Only a few comparative studies were performed regarding the superiority of robotic-assisted (RA) surgery over fluoroscopic guidance (FG) surgery during percutaneous pedicle screws placement. Therefore, the aim of the present study was to conduct a systematic literature review and meta-analysis to evaluate the accuracy and potential advantages of RA compared with FG.

Editorial on: Musculoskeletal Rehabilitation: Current Challenges and New Perspectives.

Musculoskeletal disorders are among the leading causes of disability and chronic pain worldwide, and their impact is expected to increase in the coming years [...

Arrayed CRISPR/Cas9 Screening for the Functional Validation of Cancer Genetic Dependencies.

CRISPR/Cas9 screening has revolutionized functional genomics in biomedical research and is a widely used approach for the identification of genetic dependencies in cancer cells. Here, we present an efficient and versatile protocol for the cloning of guide RNAs (gRNA) into lentiviral vectors, the production of lentiviral supernatants, and the transduction of target cells in a 96-well format. To assess the effect of gene knockouts on cellular fitness, we describe a competition-based cell proliferation assay using flow cytometry, enabling the screening of many genes at the same time in a fast and reproducible manner.

Increased Frequency of Hand Hygiene and Other Infection Prevention Practices Correlates with Reduced Surgical Wound Infection Rates in Spinal Surgery during the COVID-19 Pandemic.

Background: Due to the COVID-19 pandemic outbreak, many changes were done in the hospital practice, and new guidelines were issued in order to contain the infection spread. One of the most common measures is represented by a correct and frequent hand washing. Recently, an association between increased adherence to hand hygiene (HH) protocols and reduction in hospital infections was documented however no studies about the surgical wound infection rate were reported in the Literature.

Complex Regional Pain Syndrome after Spine Surgery: A Rare Complication in Mini-Invasive Lumbar Spine Surgery: An Updated Comprehensive Review.

Background: Complex regional pain syndrome (CRPS) is a postoperative, misdiagnosed condition highlighted only by pain therapists after numerous failed attempts at pain control by the treating surgeon in the case of prolonged pain after surgery. It only occurs rarely after spine surgery, causing the neurosurgeon's inappropriate decision to resort to a second surgical treatment.

Methods: We performed a systematic review of the literature reporting and analyzing all recognized and reported cases of CRPS in patients undergoing spinal surgery to identify the best diagnostic and therapeutic strategies for this unusual condition.

Liner dissociation in total hip arthroplasty: a systematic review.

Objective: Liner dissociation (LD) is a rare catastrophic mechanical failure of total hip arthroplasty (THA). The study aims at reviewing the available literature regarding liner dissociations to point out their prevalence, describing any possible association and highlighting the surgical management at the time of revision.

Materials And Methods: A systematic review of the literature was conducted from January 2002, until February 2022, according to the PRISMA guidelines.