Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a “signature pathway” associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice

Distinct Cis Regulatory Elements Govern the Expression of TAG1 in Embryonic Sensory Ganglia and Spinal Cord

Cell fate commitment of spinal progenitor neurons is initiated by long-range, midline-derived, morphogens that regulate an array of transcription factors that, in turn, act sequentially or in parallel to control neuronal differentiation. Included among these are transcription factors that regulate the expression of receptors for guidance cues, thereby determining axonal trajectories. The Ig/FNIII superfamily molecules TAG1/Axonin1/CNTN2 (TAG1) and Neurofascin (Nfasc) are co-expressed in numerous neuronal cell types in the CNS and PNS – for example motor, DRG and interneurons - both promote neurite outgrowth and both are required for the architecture and function of nodes of Ranvier. The genes encoding TAG1 and Nfasc are adjacent in the genome, an arrangement which is evolutionarily conserved. To study the transcriptional network that governs TAG1 and Nfasc expression in spinal motor and commissural neurons, we set out to identify cis elements that regulate their expression. Two evolutionarily conserved DNA modules, one located between the Nfasc and TAG1 genes and the second directly 59 to the first exon and encompassing the first intron of TAG1, were identified that direct complementary expression to the CNS and PNS, respectively, of the embryonic hindbrain and spinal cord. Sequential deletions and point mutations of the CNS enhancer element revealed a 130bp element containing three conserved E-boxes required for motor neuron expression. In combination, these two elements appear to recapitulate a major part of the pattern of TAG1 expression in the embryonic nervous system

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Plasma Technology Reduces Blood Loss in Adolescent Idiopathic Scoliosis Surgery: A Prospective Randomized Clinical Trial

Study Design: Prospective randomized clinical trial. Objectives: To assess the effectiveness of PEAK Plasmablade (PPB), compared with bipolar sealer and standard electrocautery, in the posterior spinal instrumentation and fusion (PSF) surgery performed for adolescent idiopathic scoliosis (AIS). Methods: Ninety-three patients undergoing PSF surgery for AIS were randomized in 2 groups: group-A patients (n = 45) underwent PSF surgery using PPB; group-B patients (n = 48) were treated with bipolar sealer and standard electrocautery. Demographic and surgical data was recorded. All the patients underwent serial blood tests on the day before surgery (T0) and at 24 (T1), 48 (T2), 72 (T3), and 96 (T4) hours postoperatively. Visual analogue scale for pain (VAS) score, the percentage of paracetamol assumption, and the blood transfusion rate were recorded in the time-lapse T1 to T4. Intergroup variability was assessed. Pearson correlation test was performed. A P value <.05 was considered significant. Results: In group A, a significantly shorter total operative time (P =.0087), a significantly lower total intraoperative blood loss (TBL) (P =.001), and a higher postoperative hemoglobin (Hb) (P =.01) were recorded. A significant higher mean Hb concentration and mean albumin value was recorded in group A at 24 and 48 hours postoperatively. A significant correlation between TBL and hospital stay was recorded in both groups (group A, P =.00 001; group B, P =.00 006); moreover, in both groups, a significant correlation was observed between TBL and mean VAS at 72 hours postoperatively (group A, P =.0009; group B, P =.0001) and at 96 hours postoperatively (group A, P =.000 044; group B, P =.00 001). Conclusions: PPB reduces the intraoperative blood loss in PSF performed for AIS, thus allowing a patient’s faster recovery

Characterization and role of Helix contactin-related proteins in cultured Helix pomatia neurons

We report on the structural and functional properties of the Helix contactin-related proteins (HCRPs), a family of closely related glycoproteins previously identified in the nervous system of the land snail Helix pomatia through antibodies against the mouse F3/contactin glycoprotein. We focus on HCRP1 and HCRP2, soluble FNIII domains-containing proteins of 90 and 45 kD bearing consensus motifs for both N- and O-glycosylation. Using the anti-HCRPs serum, we find secreted HCRPs in Helix nervous tissue isotonic extracts and in culture medium conditioned by Helix ganglia. In addition, we demonstrate expression of HCRPs on neuronal soma and on neurite extensions. Functionally, in Helix neurons, the antisense HCRP2 mRNA counteracts neurite elongation, and the recombinant HCRP2 protein exerts a strong positive effect on neurite growth when used as substrate. These data point to HCRPs as novel neurite growth-promoting molecules expressed in invertebrate nervous tissue

Spinopelvic parameter changes and low back pain improvement due to femoral neck anteversion in patients with severe unilateral primary hip osteoarthritis undergoing total hip replacement

PURPOSE: The study of the interrelation between hip and spine disorders is gaining increasing importance in the last years, but the link between Hip Osteoarthritis (HOA) and Low Back Pain (LBP) remains still unclear. Aim of the study is to assess the relationship between Femoral Neck Anteversion (FNA), LBP, and spinopelvic parameters in patients undergoing Total Hip Replacement (THR) for unilateral severe primary HOA. MATERIALS AND METHODS: 91 patients were recruited. Inclusion criteria were: grade 5 or 6 unilateral HOA, according to Turmezei, and Harris Hip score (HHS) <60. Exclusion criteria were: secondary hip osteoarthritis (dysplasia of the hip, rheumatoid arthritis, and ankylosing spondylitis); previous surgery of the spine, hip or knee; scoliosis with a Cobb angle greater than 10°; spondylolisthesis; history of spine fractures; previous bone tuberculosis or any spine infections; any contraindications to CT; BMI >30. Patients were divided into two homogeneous Groups according to the presence (Group-A) or not of concomitant LBP (Group-B). All patients underwent preoperatively a hip CT scan to evaluate FNA, Acetabular Anteversion (AA), and Combined Anteversion (CA = FNA + AA). ΔFNA, ΔAA and ΔCA were calculated as the differences between the arthritic hip and the normal hip angles in each Group. Full spinal X-rays in upstanding position were performed before (baseline) and 6 months after THR (follow-up) to calculate spinopelvic parameters. The health-related quality of life (HRQoL) was evaluated at baseline and at follow-up using Visual Analogue Scale (VAS), HHS, Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RM), and Short-Form Health Survey (SF-36). The intra-group and inter-group variability were assessed using, respectively, paired and unpaired t tests. At baseline, the association between HRQoL scores and ΔFNA, ΔAA, and ΔCA was analysed by the Pearson correlation test. RESULTS: At baseline, in Group-A, there was a significant difference between arthritic FNA and normal hip FNA, while no differences were found in AA between the two hips. A close correlation was observed between ΔFNA and Spine-VAS (r = 0.788), ODI (r = 0.824), and RM (r = 0.775). In Group-B, there was not a significant difference in FNA and AA between the two hips. At recruitment, in Group-A patients, we recorded a higher LL, SS, PI, SVA(C7), and a lower PT and T1-SPI compared with Group-B subjects. Six months after THR, in Group-A, an improvement of all clinical scores was recorded, as well as, a significant reduction of SS, LL, T1PA, and SVA(C7) and an increment of PT. In Group-B, at follow-up, an improvement of HHS, Hip-VAS, and SF-36 was recorded, while the changes in spinopelvic parameters were not significant. CONCLUSIONS: Patients with concomitant unilateral HOA and LBP showed a marked anteverted FNA in the arthritic hip and a spinopelvic misalignment. After THR, a relief of both hip and low back pain and a change in spinopelvic parameters is observed

F3/Contactin-related proteins in Helix pomatia nervous tissue (HCRPs): Distribution and function in neurite growth and neurotransmitter release

By using antibodies against mouse F3/contactin, we found immunologically related glycoproteins expressed in the nervous tissue of the snail Helix pomatia. Helix contactin-related proteins (HCRPs) include different molecules ranging in size from 90 to 240 kD. Clones isolated from a cDNA expression library allowed us to demonstrate that these proteins are translated from a unique 6.3-kb mRNA, suggesting that their heterogeneity depends on posttranslational processing. This is supported by the results of endoglycosidase F treatment, which indicate that the high-molecular-weight components are glycosylation variants of the 90-kD chain. In vivo and in cultures, HCRPs antibodies label neuronal soma and neurite extensions, giving the appearance of both cytoplasmic and cell surface immunostaining. On the other hand, no expression is found on nonneural tissues. Functionally, HCRPs are involved in neurite growth control and appear to modulate neurotransmitter release, as indicated by the inhibiting effects of specific antibodies on both functions. These data allow the definition of HCRPs glycoproteins as growth-promoting molecules, suggesting that they play a role in neurite development and presynaptic terminal maturation in the invertebrate nervous system

Everolimus therapy and side-effects: A systematic review and meta-analysis

Recent studies have focused on identifying novel targeted agents in order to reduce the undesired side-effects of conventional chemotherapeutic agents on normal cells. However, even targeted therapies may exert certain negative effects on healthy tissues. The present systematic review was performed in order to evaluate the type and the incidence of side-effects in patients treated with everolimus. The PubMed and Scopus databases were searched using the following free words and MESH terms: 'everolimus' AND 'side-effects' OR 'toxicities' OR 'adverse events'. A total of 912 potentially relevant studies that were screened based on the title and abstracts were identified. A total of 731 were excluded as they did not fulfil the inclusion criteria. Of the 181 remaining studies included, the adverse events reported were obtained. The primary adverse events reported were stomatitis, leuko- penia, anorexia, anaemia and fatigue. The majority of the patients reported adverse events limited to grade 1 or 2. On the whole, the data presented herein confirm the findings of previous studies on the relative safety of everolimus, a targeted therapeutic agent, which differs from that of conventional chemotherapy, and highlight the potential adverse events asso- ciated with the therapeutic use of everolimus. © 2021 Spandidos Publications. All rights reserved