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

AB0134\u2005Phosphorelated stat3 expression in peripheral blood mononuclear cells in rheumatoid arthritis

Conference: Annual European Congress of Rheumatology, EULAR 2018, Amsterdam, 13\u201316 June 201

The autoclaving and re-implantation of an infected prosthesis as a spacer during resection knee arthroplasty: a systematic review

Background: Hofmann et al., in 1995, first described an articulating spacer made by cleaning and autoclaving the original femoral component, which is then re-implanted with a new tibial polyethylene. This systematic review aims to assess the state of existing evidence on the intraoperative autoclaving and re-use of an infected prosthesis, as a spacer, during a two-stage revision following Periprosthetic Joint Infections (PJI). Methods: A systematic review was conducted with methods described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. OVID-MEDLINE®, EMBASE, Cochrane Library, SCOPUS, Web of Science, Google Scholar and PubMed were searched from 1995 to April 2020 to identify relevant studies. Results: Fourteen studies were included in this systematic review: two prospective case series; six retrospective comparative studies and six retrospective case series. The reviewed studies included 567 patients (571 knees): 394 patients treated with autoclaved components and 173 with a spacer made of new components. The cumulative re-infection rate in patients treated with re-used autoclaved components was 13.7% (54 re-infections in 394 patients), whereas in control patients the re-infection rate was 13.3% (23 re-infections in 173 patients). The final Range of Movement in patients treated using the autoclaved components as a spacer, compared with patients receiving static spacers, was significantly higher in three out of four comparative studies. Conclusion: There is a moderate level of evidence that the intraoperative autoclaving and re-use of an infected prosthesis as a spacer, during a knee resection arthroplasty, is an effective procedure in the management of knee PJI

Bridging the gap between serum biomarkers and biomechanical tests in musculoskeletal ageing.

Musculoskeletal ageing is a major public health interesting and strain due to the significant demographic modifications in the population, and it is linked to high risk of falls, loss of autonomy in elderly individuals and institutionalization with small health outcomes. Thus, this pathological status is related to high morbidity and health care rates. Bone mass and muscle mass and strength increase during late adolescence and early adulthood but start to reduce noticeably from the fifth decade of life and are closely linked. Preclinical and clinical data strongly support the muscle-bone cross-talk showing the presence of many tissue-specific factors released by the muscle that modulate bone, such as insulin-like growth factor-1 (IGF- 1), IL-6, IL-15, myostatin and irisin. Bone and muscle tissues were increasingly recognized as endocrine target organs and endocrine organs themselves, interacting through paracrine and endocrine signals. It is then plausible that laboratory parameters could be involved in sarcopenia and osteoporosis diagnosis and treatment monitoring. This narrative review raises the possibility of whether this poor correlation between different muscle/lean mass assessment methods and muscle function tests could suggest that each parameter evaluates different aspects of "muscle status" or "muscle quality". If this is true, no one test can be used to assess muscle status but rather a battery of tests is necessary for a comprehensive assessment. More research is required to provide information for researchers to optimally design studies by using the muscle assessment method that is best associated with selected specific outcomes

Box-loop technique in the management of complex elbow instability: A prospective controlled trial

Introduction: Chronic elbow instability is a disable complication. This prospective study reports our experience with the box-loop reconstruction technique, compared with traditional Lateral Collateral Ligament (LCL) and eventual Medial Collateral Ligament (MCL) reconstruction, showing its functional outcome at 12-month follow-up. Methods: From January 2013 to February 2017, 27 patients with complex elbow instability were recruited. Group-A patients were managed using box-loop technique; in Group-B patients LCL reconstruction was performed and MCL lesions were always intraoperatively tested, under fluoroscopy, and eventually treated. Clinical evaluations were performed at baseline (T0) and at 1- month (T1), 6-month (T2) and 12-month (T3) follow- up. X-rays were performed at T0 and T3. Intergroup and intragroup variability was assessed. Results: In all the patients, an improvement of both the range of movement and the joint stability was observed after surgery. The mean increase in flexion-extension arch was 52° in Group-A patients at 12-month follow-up. A significant improvement (p<0.05) of Mayo Elbow Performance Score, Oxford Elbow Scores and Visual Analogue Scale was observed at 12-month follow-up in both groups. Conclusion: Box-loop technique revealed safe and effective in the management of multidirectional elbow instability