Bmc Med
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In non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs), higher blood tumor mutational burden (bTMB) was usually associated with better progression-free survival (PFS) and objective response rate (ORR). However, the association between bTMB and overall survival (OS) benefit remains undefined. It has been reported that patients harboring a high level of circulating tumor DNA (ctDNA) had poor survival. We hypothesized that ctDNA-adjusted bTMB might predict OS benefit in NSCLC patients receiving ICIs. ⋯ Our study indicated that ctDNA-adjusted bTMB might predict OS benefit in NSCLC patients receiving ICIs. The potential of ctDNA-adjusted bTMB as a noninvasive predictor for immunotherapy should be confirmed in future studies.
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Necrotising soft tissue infections (NSTIs) are rapidly progressing bacterial infections usually caused by either several pathogens in unison (polymicrobial infections) or Streptococcus pyogenes (mono-microbial infection). These infections are rare and are associated with high mortality rates. However, the underlying pathogenic mechanisms in this heterogeneous group remain elusive. ⋯ At the population level, we found aetiology-dependent responses showing the potential modes of entry and immune evasion strategies employed by S. pyogenes, congruent with general cellular processes such as differentiation and proliferation. After stratifying the patients based on the subject-specific networks to study the patient-specific response, we observed different patient groups with different collagens, cytoskeleton and actin monomers in association with virulence factors, immunogenic proteins and housekeeping genes which we utilised to postulate differing modes of entry and immune evasion for different bacteria in relationship to the patients' phenotype.
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Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic. ⋯ One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.
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Recommended cardiovascular disease (CVD) prediction tools do not account for competing mortality risk and over-predict incident CVD in older and multimorbid people. The aim of this study was to derive and validate a competing risk model (CRISK) to predict incident CVD and compare its performance to that of QRISK3 in UK primary care. ⋯ CRISK and CRISK-CCI performed better than QRISK3. CRISK-CCI recommends fewer people for treatment and has a lower NNT to prevent a new CVD event compared to QRISK3. Competing risk models should be recommended for CVD primary prevention treatment recommendations.