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BACKGROUND: Unfortunately, the majority of patients with colorectal cancer liver metastases (CRCLM) experience disease recurrence following hepatic surgery. The key challenge is therefore optimal patient selection, which currently relies on anatomical and clinical parameters. Exploring a potential molecular signature may be predictive for seeing a clinical benefit from CRCLM resection. METHODS: Consecutive patients who underwent CRCLM resection at our medical center between 2006 and 2016 were divided into cohorts of "good prognosis" (GP) or "poor prognosis" (PP) based on the time interval between their resection and disease recurrence. Proteomic analysis was performed on the surgical specimen and correlation analysis was carried out with demographics and clinical outcomes. RESULTS: Proteomic analysis revealed 99 differentially expressed proteins of which a third were associated with extracellular matrix (ECM) pathways as the matrix metalloproteinases (MMPs). Multivariate analysis yielded a statistically differential proteomic pattern between the cohort regardless of perioperative treatment. CONCLUSION: Our results indicate a different proteomic landscape in the cohort of patients who had a clinical benefit from CRCLM resection which appears to be correlated with ECM pathways. Further prospective studies are needed to define the role of ECM pathways in prognostics and patient selection for surgical procedures for CRCLM.
RESUMO
BackgroundMassive vaccination rollouts against SARS-CoV-2 infections have facilitated the easing of control measures in countries like Israel. While several studies have characterized the effectiveness of vaccines against severe forms of COVID-19 or SARS-CoV-2 infection, estimates of their impact on transmissibility remain limited. Here, we evaluated the role of vaccination and isolation on SARS-CoV-2 transmission within Israeli households. MethodsFrom December 2020 to April 2021, confirmed cases were identified among healthcare workers of the Sheba Medical Centre and their family members. Households were recruited and followed up with repeated PCR for a minimum of ten days after case confirmation. Symptoms and vaccination information were collected at the end of follow-up. We developed a data augmentation Bayesian framework to ascertain how age, isolation and BNT162b2 vaccination with more than 7 days after the 2nd dose impacted household transmission of SARS-CoV-2. Findings210 households with 215 index cases were enrolled. 269 out of 687 (39%) household contacts developed a SARS-CoV-2 infection. Of those, 170 (63%) developed symptoms. Children below 12 years old were less susceptible than adults/teenagers (Relative Risk RR=0{middle dot}50, 95% Credible Interval CI 0{middle dot}32-0{middle dot}79). Vaccination reduced the risk of infection among adults/teenagers (RR=0{middle dot}19, 95% CI 0{middle dot}07-0{middle dot}40). Isolation reduced the risk of infection of unvaccinated adult/teenager (RR=0{middle dot}11, 95% CI 0{middle dot}05-0{middle dot}19) and child contacts (RR=0{middle dot}16, 95% CI 0{middle dot}07-0{middle dot}31) compared to unvaccinated adults/teenagers that did not isolate. Infectivity was significantly reduced in vaccinated cases (RR=0{middle dot}22, 95% CI 0{middle dot}06-0{middle dot}70). InterpretationWithin households, vaccination reduces both the risk of infection and of transmission if infected. When contacts were not vaccinated, isolation also led to important reductions in the risk of transmission. Vaccinated contacts might reduce their risk of infection if they isolate, although this requires confirmation with additional data. FundingSheba Medical Center. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe efficacy of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissions in households remains understudied. On June 28, 2021, we searched PubMed and medRxiv for articles published between December 1, 2020, and June 28, 2021, using the following combination of search terms: ("COVID-19" OR "SARS-CoV-2") AND ("household*" OR "famil*") AND "transmission" AND "vaccination". Our search yielded two articles that investigated the effect of vaccination on SARS-CoV-2 transmission in households. They showed a lower risk of infection in households with vaccinees. Vaccine efficacy on the risk of infection was estimated to 80% after the 2nd dose, and vaccine efficacy on the risk of transmission if infected was estimated to 49% 21 days after the 1st dose. However, these estimates are derived from surveillance data with no active follow-up of the households. In addition, the impact of isolation precautions has not been assessed. Added value of this studyBased on the active follow-up of households of health care workers from the Sheba Medical Center in Israel, we estimated the effect of vaccination on household transmission. To our knowledge, our study is the first to conjointly investigate the effect of vaccination, age, and isolation precautions on the risk of infection and the risk of transmission in households while accounting for tertiary infections in the household, infections within the community, the reduced infectivity of asymptomatic cases, misidentification of index cases, and household size. Our study confirmed the high efficacy of BNT-162b2 vaccination to reduce infection risk and transmission risk. It also suggests that isolation might remain beneficial to vaccinated contacts. Implications of all the available evidenceVaccination reduces susceptibility to infection and case infectivity in households. Isolation precautions also mitigate the risk of infection and should be implemented whenever a household member is infected. They might remain beneficial to vaccinated contacts.
