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While the delay in adjuvant chemotherapy (AC) is known to impact colon cancer outcomes, its effect on rectal cancer is less clear. This study aims to evaluate the influence of AC timing on survival in stage II and III rectal cancer. This retrospective multicenter study enrolled 1,144 patients receiving chemotherapy following resection of stage II–III rectal cancers. The effect of delayed AC on survival was assessed using multivariable Cox models with restricted cubic splines and logistic regression. Compared to patients initiating AC within four weeks postsurgery, those initiating within 5–8 weeks had a similar survival (HR=0.85, 95 % CI=0.66–1.11), whereas those initiating within 8–12 weeks (HR=1.62, 95 % CI=1.05–2.51) or beyond 12 weeks (HR=2.07, 95 % CI=1.21–3.56) had a significantly inferior survival. A delayed time to chemotherapy (>8 weeks) was associated with worse survival in patients aged ≥60 years but not in younger patients (<60 years: HR=1.36; 95 % CI=0.75–2.46, p=0.312; ≥60 years: HR=2.37; 95 % CI=1.56–3.60, p<0.001). Additionally, our exploratory analysis suggested that FOLFOX and FOLFIRI were more effective when starting within 5–8 weeks post-surgery, while CAPEOX and a single agent showed a slight advantage when starting within four weeks. Our findings advocate for initiating AC within eight weeks post-surgery in stage II–III rectal cancer, especially in older patients. Delayed treatment is linked to significantly worse survival outcomes. [ABSTRACT FROM AUTHOR]

We evaluate the prognostic value of chemotherapy and other prognostic factors on overall survival among colon patients with deficient mismatch repair (dMMR), and determine the optimum time to start chemotherapy after surgery. Data of 306 colon cancer patients with dMMR who received radical surgery were collected from three Chinese centers between August 2012 and January 2018. Overall survival (OS) was assessed with the Kaplan–Meier method and log-rank. Cox regression analysis were used to assess influencing prognosis factors. The median follow-up time for all patients was 45.0 months (range, 1.0–100). There was a nonsignificant OS benefit from chemotherapy for patients with stage I and stage II disease, including high-risk stage II disease (log-rank p: 0.386, 0.779, 0.921), and a significant OS benefit for patients with stage III and stage IV disease for receiving post-operation chemotherapy (log-rank p = 0.002, 0.019). Stage III patients benefitted from chemotherapy regimens that contained oxaliplatin (log-rank p = 0.004), and Starting chemotherapy with oxaliplatin treatment earlier resulted in better outcomes (95% CI 0.013–0.857; p = 0.035). Chemotherapy regimens containing oxaliplatin can prolong the survival time of stage III and IV dMMR colon cancer patients. This beneficial manifestation was more pronounced after starting chemotherapy treatment early post operation. High risk stage II dMMR colon patients including T4N0M0 cannot benefit from chemotherapy. [ABSTRACT FROM AUTHOR]

Monocarboxylate transporters (MCTs) play vital roles in carbon source assimilation, drug resistance and virulence. However, the underlying function of MCTs in fungal pathogenesis and development has not been investigated in detail. In this study, we identified and characterized the monocarboxylate transporter gene MCT1 of Colletotrichum gloeosporioides, which is the causal agent of Glomerella leaf spot of apple. Mct1 is localized to the mitochondria and may mediate the uptake of lactate to the cell. However, MCT1 was constitutively expressed but showed an enhanced expression level in response to the presence of the extracellular lactate. Our results indicate that Mct1 plays a role in the metabolism of lactate. More importantly, the Δmct1 mutant showed significantly poor conidiation and a defect in host infection. Taken together, our studies provide evidence for Mct1 as a mitochondrial transmembrane protein mediating conidiation, the metabolism of lactate, and the pathogenicity of C. gloeosporioides. [ABSTRACT FROM AUTHOR]

Purpose/aim of the study:Cerebrovascular reactivity (CVR) reflects the vasodilatory reserve of cerebral resistance vessels, which is an important marker for assessing cerebrovascular disease. The present study is to investigate whether CVR impairment increases adverse long-term outcome risk of patients with ≥ 50% symptomatic unilateral middle cerebral artery (MCA) stenosis (ischemic stroke (IS) or transient ischemic attack (TIA)). Material and methods:Digital subtraction angiography (DSA) was used to assess the degree of stenosis, and perfusion CT and 5% CO2inhalation were adopted to evaluate CVR. Patients with ≥ 50% symptomatic unilateral MCA stenosis were assigned to non-CVR impairment group and CVR impairment group according to CVR status. The long-term follow-up endpoint was composite of any IS ( in the territory of the studied MCA) or death within 12 months. Results:Seventy-three patients with ≥ 50% symptomatic unilateral MCA stenosis, involving 31 non-CVR impairment cases and 42 CVR impairment cases, were included in the present study. Finally, IS occurred in six CVR impairment patients, and no endpoint happened in the non-CVR impairment group. Therefore, the annual rate of IS was 14.29% in the CVR impairment group and 0% in the non-CVR impairment group (P= 0.035). Besides, further Kaplan-Meier analysis found CVR impairment was closely associated with the IS risk (Kaplan-Meier Log-rank 4.719,P= 0.030). Conclusions:Our results showed that for patients with ≥ 50% symptomatic unilateral MCA stenosis, there was significant difference between non-CVR impairment cases and CVR impairment cases in the annual rate of IS. It suggests that CVR impairment increases the risk of adverse long-term outcomes. [ABSTRACT FROM PUBLISHER]