Translationally Controlled Tumor-Associated Protein

EditorialInternational audienceTranslationally-controlled tumor-associated protein (TCTP) has been discovered in 1983 in mouse erythroleukemia cells. Over the years, it became evident that TCTP is an important player in a number of basic cell physiology events in cancer, embryo development, cell cycle, apoptosis, proliferation, growth, stress response, allergy, gene regulation, and heat-shock response. However, despite the nearly three decades of research, we only start to understand the role of TCTP in physiology of animal and plant embryo development as well as in numerous pathologies through its participation in cell cycle, proliferation, and growth regulation. The exact roles of TCTP in many complex cellular processes still remain a mystery. One of the key questions in cancer research is the role of TCTP in tumor reversion, the rare event leading to tumor regression and a “miraculous” cure: is TCTP involved in gene regulation or rather modification of the cytoskeleton of cancer cells during this process? It seems plausible that a novel type of posttranslational modification of TCTP, such as SUMOylation, by regulating its nuclear localization and/or its association with the centrosomes (both subjects featured in this issue) is responsible for some of the TCTP functions in normal and cancer cells. From presented in this issue very comprehensive and up-to-date reviews on TCTP functions, it clearly transpires that TCTP has a potential to be a crucial target for anticancer therapies. However, more research on the regulation of TCTP and its involvement in various molecular and cellular pathways and its association with subcellular structures is needed for the improvement of our understanding of this oncogene and the development of novel TCTP-targeted cancer therapies. We hope that our special TCTP issue will help in stimulation of scientific research in this field

COVID-19 mortality may be reduced among fully vaccinated solid organ transplant recipients.

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risk for morbidity and mortality from COVID-19 due to their immunosuppressed state and reduced immunogenicity from COVID-19 mRNA vaccines. This investigation examined the association between COVID-19 mRNA vaccination status and mortality among SOT recipients diagnosed with COVID-19. METHODS & FINDINGS: A retrospective, registry-based chart review was conducted investigating COVID-19 mortality among immunosuppressed solid organ transplant (SOT) recipients in a large metropolitan healthcare system in Houston, Texas, USA. Electronic health record data was collected from consecutive SOT recipients who received a diagnostic SARS-CoV-2 test between March 1, 2020, and October 1, 2021. The primary exposure was COVID-19 vaccination status at time of COVID-19 diagnosis. Patients were considered \u27fully vaccinated\u27 at fourteen days after completing their vaccine course. COVID-19 mortality within 60 days and intensive care unit admission within 30 days were primary and secondary endpoints, respectively. Among 646 SOT recipients who were diagnosed with COVID-19 at Houston Methodist Hospital between March 2020, and October 2021, 70 (10.8%) expired from COVID-19 within 60 days. Transplanted organs included 63 (9.8%) heart, 355 (55.0%) kidney, 108 (16.7%) liver, 70 (10.8%) lung, and 50 (7.7%) multi-organ. Increasing age was a risk factor for COVID-19 mortality, while vaccination within 180 days of COVID-19 diagnosis was protective in Cox proportional hazard models with hazard ratio 1.04 (95% CI: 1.01-1.06) and 0.31 (0.11-0.90), respectively). These findings were confirmed in the propensity score matched cohort between vaccinated and unvaccinated patients. CONCLUSIONS: This investigation found COVID-19 mortality may be significantly reduced among immunosuppressed SOT recipients within 6 months following vaccination. These findings can inform vaccination policies targeting immunosuppressed populations worldwide

Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes

Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupervised binary matrix factorization (BMF) clustering and identify six distinct genetic subtypes. These subtypes are differentially associated with established MM-related RNA signatures, oncogenic and immune transcriptional profiles, and evolving clinical biomarkers. Three genetic subtypes are associated with increased risk of progression to active MM in both the primary and validation cohorts, indicating they can be used to better predict high and low-risk patients within the currently used clinical risk stratification models

Improvement in Survival Associated With Adult-to-Adult Living Donor Liver Transplantation

More than 2000 adult-to-adult living donor liver transplants (LDLT) have been performed in the U.S., yet the potential benefit to liver transplant candidates of undergoing LDLT compared to waiting for deceased donor liver transplant (DDLT) is unknown. The aim of this study was to determine if there is a survival benefit of adult LDL

Intraoperative Vancomycin Use in Spinal Surgery: Single Institution Experience and Microbial Trends.

Study Design. Retrospective Case Series.Objective. To demonstrate the microbial trends of spinal surgical site infections(SSI) in patients who had previously received crystallized vancomycin in the operative bed.Summary of Background Data. Prior large, case control series demonstrate the significant decrease in SSI with the administration of vancomycin in the wound bed.Methods. A single institution, electronic database search was conducted for all spinal surgery patients who had received prophylactic crystalline vancomycin powder in the wound bed. Patient\u27s with a prior history of wound infection, intrathecal pumps, or spinal stimulators were excludedResults. 981 consecutive patients (494 male, 487 female, mean age 59.4 years, range 16-95 years) were identified from January 2011 to June 2013. The average dose of vancomycin powder was 1.13 grams(range: 1-6 grams). 66 patients (6.71%) were diagnosed with a SSI of which 51 patients had positive wound cultures (5.2%). Of the 51 positive cultures the most common organism was Staphylococcus aureus. The average dose of vancomycin was 1.3 grams in the 38 cases where a gram-positive organism was cultured. A number of gram-negative infections were encountered such as Serratia marcescens, Enterobacter aerogenes, Bacteroides fragilis, Enterobacter cloacae, Citrobacter koseri and Pseudomonas aeruginosa. The average dose of vancomycin was 1.2 grams in 23 cases where a gram negative infection was cultured. 15 of the 51 (29.4%) positive-cultures were polymicrobial. 8 (53%) of these 15 polymicrobial cultures contained three or more distinct organisms.Conclusion. Prophylactic intraoperative vancomycin use in the wound bed in spinal surgery may increase the incidence of gram-negative or polymicrobial spinal infections. The use of intraoperative vancomycin may correlate with postoperative seromas, due to the high incidence of non-positive cultures. Large, randomized, prospective trials are needed to demonstrate causation and dose-response relationship

Minimal residual disease in Myeloma: Application for clinical care and new drug registration

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries