HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy.

Clear cell renal cell carcinoma (ccRCC), despite having a low mutational burden, is considered immunogenic because it occasionally undergoes spontaneous regressions and often responds to immunotherapies. The signature lesion in ccRCC is inactivation of the VHL tumor suppressor gene and consequent upregulation of the HIF transcription factor. An earlier case report described a ccRCC patient who was cured by an allogeneic stem cell transplant and later found to have donor-derived T cells that recognized a ccRCC-specific peptide encoded by a HIF-responsive endogenous retrovirus (ERV), ERVE-4.

Efficacy of Treatments After Lenvatinib in Patients with Advanced Renal Cell Carcinoma.

Background And Objective: Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) used in the upfront and refractory settings for metastatic renal cell carcinoma (mRCC). However, there are limited data on the efficacy of subsequent TKI therapies after lenvatinib. We investigated the activity of TKI therapies after lenvatinib in patients with mRCC.

Single-cell epigenetic profiling reveals an interferon response-high program associated with deficiency in kidney cancer.

Renal cell carcinoma (RCC) is characterized by recurrent somatic mutations in epigenetic regulators, which stratify patients into clinically significant subgroups with distinct prognoses and treatment responses. However, the cell type-specific epigenetic landscape of RCC-broadly and in the context of these mutations-is incompletely understood. To investigate these open questions, we integrated single nucleus ATAC sequencing data from RCC tumors across four independent cohorts.

Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers.

Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

Background: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens.

Materials And Methods: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively.

Impact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes.

Saliby et al. show that a machine learning approach can accurately classify clear cell renal cell carcinoma (RCC) into distinct molecular subtypes using transcriptomic data. When applied to tumors biospecimens from the JAVELIN Renal 101 (JR101) trial, a benefit is observed with immune checkpoint inhibitor (ICI)-based therapy across all molecular subtypes.

Efficacy and safety of the enzymatic mixture - Lipase, collagenase and hyaluronidase - In the treatment of moderate to severe submental fat: A prospective cohort study.

Purpose: To study the effect of the enzymatic mixture: Lipase, Collagenase and Hyaluronidase in the treatment of submental fat.

Methods: A monocentric prospective cohort study including 10 female patients, aged between 18 and 65 years old, who received treatment for submental fat with a mixture of Lipase, Collagenase, and Hyaluronidase. The treatment protocol consisted of one treatment session every 21 days for a total of 3 sessions.

Update on Biomarkers in Renal Cell Carcinoma.

Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers.

Kinematic adaptations from self-selected to fast speed walking in patients with adult spinal deformity.

Purpose: To investigate kinematic adaptations from self-selected to fast speed walking in ASD patients.

Methods: 115 primary ASD and 66 controls underwent biplanar radiographic X-rays and 3D gait analysis to calculate trunk, segmental spine and lower limb kinematics during self-selected and fast speed walking. Kinematic adaptation was calculated as the difference (Δ) between fast and self-selected speed walking.

Clinicodemographic characteristics of extraosseous ewing sarcoma: A comparative meta-analysis of pediatric and adult patients.

Background: Evidence suggests different presentation patterns and prognosis of extraosseous Ewing Sarcoma (EES) based on age. Thus, we carried out this study to test the difference between children and adult EES cases regarding clinicodemographic characteristics and prognosis.

Methods: A total of 4 databases were explored yielding 18 relevant studies for data synthesis.

Emerging Biomarkers of Response to Systemic Therapies in Metastatic Clear Cell Renal Cell Carcinoma.

Patients with metastatic clear cell renal cell carcinoma (mccRCC) experience highly heterogeneous outcomes when treated with standard-of-care systemic regimens. Therefore, valid biomarkers are needed to predict the clinical response to these therapies and help guide management. In this review, the authors outline relevant and promising biomarkers for patients with mccRCC receiving systemic therapies, with a focus on immunotherapy-based regimens.

Novel Immune Therapies for Renal Cell Carcinoma: Looking Beyond the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Axes.

Immunotherapy has revolutionized treatment for patients with advanced and metastatic renal cell carcinoma. Nevertheless, many patients do not benefit or eventually relapse, highlighting the need for novel immune targets to overcome primary and acquired resistance. This review discusses 2 strategies currently being investigated: disabling inhibitory stimuli that maintain immunosuppression ("brakes") and priming the immune system to target tumoral cells ("gas pedals").

Novel Targeted Therapies for Renal Cell Carcinoma: Building on the Successes of Vascular Endothelial Growth Factor and mTOR Inhibition.

Targeted therapies have revolutionized the treatment of renal cell carcinoma (RCC). The VHL/HIF pathway is responsible for the regulation of oxygen homeostasis and is frequently altered in RCC. Targeting this pathway as well as the mTOR pathway have yielded remarkable advances in the treatment of RCC.

ASD with high pelvic retroversion develop changes in their acetabular orientation during walking.

Introduction: It was hypothesized that pelvic retroversion in Adult Spinal Deformity (ASD) can be related to an increased hip loading explaining the occurrence of hip-spine syndrome.

Research Question: How pelvic retroversion can modify acetabular orientation in ASD during walking?

Methods: 89 primary ASD and 37 controls underwent 3D gait analysis and full-body biplanar X-rays. Classic spinopelvic parameters were calculated from 3D skeletal reconstructions in addition to acetabular anteversion, abduction, tilt, and coverage.

Phenotype Prevalence and Health-Related Quality of Life of Lebanese Women With Polycystic Ovary Syndrome.

Objective: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders. Our study aimed to assess, for the first time, the phenotype prevalence and the health-related quality of life of Lebanese women with PCOS.

Methods: This was a cross-sectional study conducted on 322 Lebanese women with PCOS, using a questionnaire containing sociodemographic data, comorbidities, disease-related clinical questions, and the validated PCOS questionnaire (PCOSQ).

Spinopelvic Adaptations in Standing and Sitting Positions in Patients With Adult Spinal Deformity.

Purpose To describe spinopelvic adaptations in the standing and sitting positions in patients with adult spinal deformity (ASD). Methods Ninety-five patients with ASD and 32 controls completed health-related quality of life (HRQOL) questionnaires: short form 36 (SF36), Oswestry Disability Index (ODI), and visual analog scale (VAS) for pain. They underwent biplanar radiography in both standing and sitting positions.

Alterations of gait kinematics depend on the deformity type in the setting of adult spinal deformity.

Purpose: To evaluate 3D kinematic alterations during gait in Adult Spinal Deformity (ASD) subjects with different deformity presentations.

Methods: One hundred nineteen primary ASD (51 ± 19y, 90F), age and sex-matched to 60 controls, underwent 3D gait analysis with subsequent calculation of 3D lower limb, trunk and segmental spine kinematics as well as the gait deviation index (GDI). ASD were classified into three groups: 51 with sagittal malalignment (ASD-Sag: SVA > 50 mm, PT > 25°, and/or PI-LL > 10°), 28 with only frontal deformity (ASD-Front: Cobb > 20°) and 40 with only hyperkyphosis (ASD-HyperTK: TK > 60°).

Assessment of dynamic balance during walking in patients with adult spinal deformity.

Purpose: To assess dynamic postural alignment in ASD during walking using a subject-specific 3D approach.

Methods: 69 ASD (51 ± 20 years, 77%F) and 62 controls (34 ± 13 years, 62%F) underwent gait analysis along with full-body biplanar Xrays and filled HRQoL questionnaires. Spinopelvic and postural parameters were computed from 3D skeletal reconstructions, including radiographic odontoid to hip axis angle (ODHA) that evaluates the head's position over the pelvis (rODHA), in addition to rSVA and rPT.

Alteration of the Sitting and Standing Movement in Adult Spinal Deformity.

Adults with spinal deformity (ASD) are known to have spinal malalignment affecting their quality of life and daily life activities. While walking kinematics were shown to be altered in ASD, other functional activities are yet to be evaluated such as sitting and standing, which are essential for patients' autonomy and quality of life perception. In this cross-sectional study, 93 ASD subjects (50 ± 20 years; 71 F) age and sex matched to 31 controls (45 ± 15 years; 18 F) underwent biplanar radiographic imaging with subsequent calculation of standing radiographic spinopelvic parameters.

Global malalignment in adolescent idiopathic scoliosis: the axial deformity is the main driver.

Purpose: To evaluate the global alignment of non-operated subjects with adolescent idiopathic scoliosis.

Method: A total of 254 subjects with AIS and 64 controls underwent low dose biplanar X-rays and had their spine, pelvis, and rib cage reconstructed in 3D. Global alignment was measured in the sagittal and frontal planes by calculating the OD-HA angle (between C2 dens to hip axis with the vertical).

Reliability assessment of cervical spine parameters measured on full-body radiographs in asymptomatic subjects and patients with spinal deformity.

Background: Cervical spinal alignment is usually assessed on full-body radiographs allowing for the concomitant evaluation of possible compensatory mechanisms that may occur at any level in the setting of postural malalignment.

Hypothesis: Cervical parameters measured on full-body radiographs are reliable.

Patients And Methods: A total of 70 subjects were included and divided in 3 groups: asymptomatic adults (n=21), adolescents with idiopathic scoliosis (n=20), and adults with spinal deformity (n=29), for whom full-body low-dose biplanar radiographs were obtained.

Gait kinematic alterations in subjects with adult spinal deformity and their radiological determinants.

Background: Adults with spinal deformity (ASD) are known to have postural malalignment affecting their quality of life. Classical evaluation and follow-up are usually based on full-body static radiographs and health related quality of life questionnaires. Despite being an essential daily life activity, formal gait assessment lacks in clinical practice.