Lumbar Spinal Rahisynthesis with Plif: a Retrospective Study of 58 Patients Demonstrating Imaging and Clinical Outcomes with One Year Follow-up.

Background/objectives: Nowadays, posterior lumbar cages remain a popular choice among the available options for interbody fusion even when compared with anterior approaches. As the posterior lumbar anatomy permits a relatively easy exposure to the spinal anatomy of interest, expandable cages prove to be a reliable tool for 360-degree fusion. Our study aspires to investigate the postoperative effects of Flarehawk 9 after open posterior lumbar fixation.

DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance.

Purpose: Patients with stage II and III cutaneous primary melanoma vary considerably in their risk of melanoma-related death. We explore the ability of methylation profiling to distinguish primary melanoma methylation classes and their associations with clinicopathologic characteristics and survival.

Materials And Methods: InterMEL is a retrospective case-control study that assembled primary cutaneous melanomas from American Joint Committee on Cancer (AJCC) 8th edition stage II and III patients diagnosed between 1998 and 2015 in the United States and Australia.

Ciliate diversity and growth rates in experimental recirculating aquaculture and aquaponics systems using microscopy.

The function of recirculating aquaculture systems (RAS) relies on microbial communities, which convert toxic, fish-excreted ammonia into substances that can provide nutrients to plants as in the case of aquaponics systems. In the present study, heterotrophic protist communities of experimental sea water RAS and freshwater aquaponics systems were investigated using microscopy to characterize their diversity, natural abundance, and potential growth rates. Heterotrophic protist abundance was low (732 ± 21 to 5451 ± 118 ciliates L and 58 ± 8 to 147 ± 18 nanoflagellates mL in the aquaponics system and 78 ± 28 to 203 ± 48 ciliates L in the RAS), which is in line with values typically reported for rivers.

Factors associated with radiation necrosis and intracranial control in patients treated with immune checkpoint inhibitors and stereotactic radiotherapy.

Background And Purpose: Emerging data suggest immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) or radiotherapy (SRT) may work synergistically, potentially increasing both efficacy and toxicity. This manuscript characterizes factors associated with intracranial control and radiation necrosis in this group.

Materials And Methods: All patients had non-small cell lung cancer, renal cell carcinoma, or melanoma and were treated from 2013 to 2021 at two institutions with ICI and SRS/SRT.

Increased tryptophan, but not increased glucose metabolism, predict resistance of pembrolizumab in stage III/IV melanoma.

Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1.

Multi-organ landscape of therapy-resistant melanoma.

Metastasis and failure of present-day therapies represent the most common causes of mortality in patients with cutaneous melanoma. To identify the underlying genetic and transcriptomic landscapes, in this study we analyzed multi-organ metastases and tumor-adjacent tissues from 11 rapid autopsies after treatment with MAPK inhibitor (MAPKi) and/or immune checkpoint blockade (ICB) and death due to acquired resistance. Either treatment elicits shared genetic alterations that suggest immune-evasive, cross-therapy resistance mechanisms.

InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma.

Introduction: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients.

StreetScouting dataset: A Street-Level Image dataset for finetuning and applying custom object detectors for urban feature detection.

The recent advancements in the field of deep learning have fundamentally altered the manner in which certain challenges and problems are addressed. One area that stands to greatly benefit from such innovations is the realm of urban planning, where the utilization of these tools can facilitate the automatic detection of landscape objects in a given area. However, it must be noted that these data-driven methodologies necessitate significant amounts of training data to attain desired results.

Surgical Site Infection Following the Correction of Adolescent Idiopathic Scoliosis With ApiFix: A Retrospective Study Analyzing Its Incidence and Recurrence.

Background and objective ApiFix (OrthoPediatrics, Warsaw, IN) is an internal brace used for the correction of adolescent idiopathic scoliosis (AIS) classified as Lenke 1 or 5 with a Cobb angle of 35-60 degrees that decreases to ≤30 degrees on lateral side-bending radiographs. Since the indications are very specific, it is not a common procedure. Our study aimed to evaluate the incidence of surgical site infection (SSI) and its recurrence following treatment with ApiFix.

Development of [F]F-5-OMe-Tryptophans through Photoredox Radiofluorination: A New Method to Access Tryptophan-Based PET Agents.

Although various radiolabeled tryptophan analogs have been developed to monitor tryptophan metabolism using positron emission tomography (PET) for various human diseases including melanoma and other cancers, their application can be limited due to the complicated synthesis process. In this study, we demonstrated that photoredox radiofluorination represents a simple method to access novel tryptophan-based PET agents. In brief, 4-F-5-OMe-tryptophans (l/d-T) and 6-F-5-OMe-tryptophans (l/d-T) were easily synthesized.

Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma.

Unlabelled: Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients and mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), and homologous recombination repair (HRR) genes via complex genomic rearrangements (CGR) and extrachromosomal DNAs (ecDNA). Almost all sensitive and acquired-resistant genomes harbor pervasive chromothriptic regions with disproportionately high mutational burdens and significant overlaps with ecDNA and CGR spans.

The Idiopathic Pulmonary Fibrosis-Associated Single Nucleotide Polymorphism RS35705950 Is Transcribed in a MUC5B Promoter Associated Long Non-Coding RNA (AC061979.1).

LncRNAs are involved in regulatory processes in the human genome, including gene expression. The rs35705950 SNP, previously associated with IPF, overlaps with the recently annotated lncRNA AC061979.1, a 1712 nucleotide transcript located within the MUC5B promoter at chromosome 11p15.

Diabetic Lumbosacral Radiculoplexus Neuropathy as an Early Onset Postoperative Complication After Posterior Lumbar Fixation and Decompression.

Diabetic amyotrophy, also known as diabetic lumbosacral radiculoplexus neuropathy (DLRN), is a condition associated with sudden pain apparition and progressive distal extremities weakness leading to ambulatory status. A wide range of causes and pathologies may be involved, rendering the diagnosis challenging. Uncontrolled type 2 diabetes mellitus (T2DM) can be a trigger factor for such disorders.

Beyond GalNAc! Drug delivery systems comprising complex oligosaccharides for targeted use of nucleic acid therapeutics.

Nucleic Acid Therapeutics (NATs) are establishing a leading role for the management and treatment of genetic diseases following FDA approval of nusinersen, patisiran, and givosiran in the last 5 years, the breakthrough of milasen, with more approvals undoubtedly on the way. Givosiran takes advantage of the known interaction between the hepatocyte specific asialoglycoprotein receptor (ASGPR) and -acetyl galactosamine (GalNAc) ligands to deliver a therapeutic effect, underscoring the value of targeting moieties. In this review, we explore the history of GalNAc as a ligand, and the paradigm it has set for the delivery of NATs through precise targeting to the liver, overcoming common hindrances faced with this type of therapy.

Targeting wild-type TP53 using AMG 232 in combination with MAPK inhibition in Metastatic Melanoma; a phase 1 study.

Background: Targeting the MDM2-p53 interaction using AMG 232 is synergistic with MAPK inhibitors (MAPKi) in preclinical melanoma models. We postulated that AMG 232 plus MAPKi is safe and more effective than MAPKi alone in TP53-wild type, MAPKi-naïve metastatic melanoma.

Methods: Patients were treated with increasing (120 mg, 180 mg, 240 mg) oral doses of AMG 232 (seven-days-on, 15-days-off, 21-day cycle) plus dabrafenib (D) and trametinib (T) (Arm 1, BRAFV600-mutant) or T alone (Arm 2, BRAFV600-wild type).

Bacterial Adaptation to Venom in Snakes and Arachnida.

Animal venoms are considered sterile sources of antimicrobial compounds with strong membrane-disrupting activity against multidrug-resistant bacteria. However, venomous bite wound infections are common in developing nations. Investigating the envenomation organ and venom microbiota of five snake and two spider species, we observed venom community structures that depend on the host venomous animal species and evidenced recovery of viable microorganisms from black-necked spitting cobra (Naja nigricollis) and Indian ornamental tarantula (Poecilotheria regalis) venoms.

Melanoma Brain Metastases: An Update on the Use of Immune Checkpoint Inhibitors and Molecularly Targeted Agents.

Brain metastases from melanoma are no longer uniformly associated with dismal outcomes. Impressive tumor tissue-based (craniotomy) translational research has consistently shown that distinct patient subgroups may have a favorable prognosis. This review provides a historical overview of the standard-of-care treatments until the early 2010s.

Traumatic Fracture of the Thoracic Spine With Severe Posterolateral Dislocation: A Case Report.

Thoracic spine fracture-dislocation injuries are always associated with high-energy trauma and result in severe neurological symptoms. Surgical reconstruction and stabilization are essential for the early mobilization and rehabilitation of patients with this type of injury. Here, we present a unique case of a 57-year-old Greek male who sustained a posterolateral T3-T4 fracture-dislocation, with a complete spinal cord injury (SCI), after falling from a height.

Theragnostic significance of tumor-infiltrating lymphocytes and Ki67 in BRAFV600-mutant metastatic melanoma (BRIM-3 trial).

We conducted a retrospective tumor tissue analysis as part of the BRIM3 trial to evaluate the theragnostic significance of tumor-infiltrating lymphocytes (TILs) and melanoma cell proliferation. Using manual semi-quantitative analyses, we assessed the density of TILs by pathology review of tissue sections stained with hematoxylin and eosin (H&E TIL score) and by immunohistochemistry (IHC) with an anti-CD8 antibody (CD8 TIL score); also, the melanoma cell proliferation by IHC with an anti-Ki67 antibody. Three hundred and fifty-three, 280, and 172 patients' tumor tissue samples were available for H&E, CD8, and Ki67 IHC analysis, respectively.

The clinical significance of adenomatous polyposis coli (APC) and catenin Beta 1 (CTNNB1) genetic aberrations in patients with melanoma.

Background: Melanoma-intrinsic activated β-catenin pathway, the product of the catenin beta 1 (CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about the association between the adenomatous polyposis coli (APC) and CTNNB1 gene mutations in stage IV melanoma with immunotherapy response and overall survival (OS).

Methods: We examined the prognostic significance of somatic APC/CTNNB1 mutations in the Cancer Genome Atlas Project for Skin Cutaneous Melanoma (TCGA-SKCM) database.

Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study.

Background: Combination nivolumab plus ipilimumab was efficacious in patients with asymptomatic melanoma brain metastases (MBM) in CheckMate 204, but showed low efficacy in patients with symptomatic MBM. Here, we provide final 3-year follow-up data from the trial.

Methods: This open-label, multicentre, phase 2 study (CheckMate 204) included adults (aged ≥18 years) with measurable MBM (0·5-3·0 cm in diameter).

Multiregional genetic evolution of metastatic uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely metastatic UM who underwent rapid autopsy.

Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204).

Background: In patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%. Here, we present the first report for patients who were symptomatic and/or required corticosteroids and updated data for asymptomatic patients.

Methods: Patients with measurable MBM, 0.