Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma

Background Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC).Methods We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance.Results ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens.Conclusions F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.Subject terms: Tumour biomarkers, Oesophageal cancer     

Optimal cut-off value of preprocedural geriatric nutritional risk index for predicting the clinical outcomes of patients undergoing endovascular revascularization for peripheral artery disease

BackgroundMalnutrition measured by the geriatric nutritional risk index (GNRI) was reported to be associated with poor prognosis for patients with peripheral artery disease (PAD). However, the optimal cut-off value of preprocedural GNRI for critical limb ischemia (CLI) and intermittent claudication (IC) is unknown. We aimed to determine its optimal cut-off value for CLI or IC patients requiring endovascular revascularization.MethodsWe explored data of 2246 patients (CLI: n = 1061, IC: n = 1185) registered in the Tokyo-taMA peripheral vascular intervention research COmraDE (TOMA-CODE) registry, which prospectively enrolled consecutive PAD patients who underwent endovascular revascularization in 34 hospitals in Japan from August 2014 to August 2016. The optimal cut-off values of GNRI were assessed by the survival classification and regression tree (CART) analyses, and the survival curve analyses for major adverse cardiovascular and limb events (MACLEs) were performed for these cut-off values.ResultsIn addition to the first cut-off value of 96.2 in CLI and 85.6 in IC, the survival CART provided an additional cut-off value of 78.2 in CLI and 106.0 in IC for further risk stratification. The survival curve was significantly stratified by the GNRI-based malnutrition status in both CLI [high risk: 47.7% (51/107), moderate: 30.1% (118/392), and low: 10.2% (53/520), log–rank p < 0.001] and IC [high risk: 14.3% (7/49), moderate: 4.5% (29/646), and low: 0.5% (2/407), log–rank p < 0.001]. The multivariate Cox-proportional hazard analysis showed that a higher GNRI was significantly associated with a better outcome in both CLI [hazard ratio (HR) per 1-point increase: 0.97, 95% CI: 0.96–0.98, p < 0.001] and IC (HR: 0.94, 95% CI: 0.91–0.97, p < 0.001).ConclusionsPreprocedural nutritional status significantly stratified future events in patients with PAD. Given that the optimal cut-off value of GNRI in CLI was almost 10-points lower than that of IC, using a disease-specific cut-off value is important for risk stratification.     

Correction to: Features of the gut prokaryotic virome of Japanese patients with Crohn’s disease

Journal of Gastroenterology -     

Three cases of COVID-19 patients presenting with erythema

Individuals infected with the novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2]) who develop coronavirus disease 2019 (COVID-19) experience many symptoms; however, cutaneous manifestations are relatively rare. The authors encountered three patients with COVID-19 who presented with erythema and suspected viral rash. In all cases, erythema appeared after the onset of the initial symptoms of COVID-19. Erythema was considered to be caused by COVID-19 and not a drug-induced eruption because, in all cases, erythema was relieved merely by external medicine and oral antihistamines, without discontinuing the original medication. The authors’ hospital accepted 69 COVID-19 patients between 22 February 2020 and 31 May 2020 and, of these, three (4.3%) exhibited eruptions, and all cases presented erythema. Except for seven patients who exhibited positive nasopharyngeal swab tests for SARS-CoV-2 RNA but no symptoms, three (4.8%) of the remaining 62 patients exhibited erythema. Although various types of eruptions have been reported in patients with COVID-19, erythema was the only type in our patients. Erythema in the three patients exhibited many similarities to that previously reported in COVID-19 patients, particularly in the manner it appeared and disappeared. For these reasons, these three cases were considered typical examples of erythema in patients with COVID-19. Considering previous studies and the three cases reported here, there is a high probability that SARS-CoV-2 can cause erythema.     

Successful endovascular repair of aortic rupture caused by axillary intra-aortic balloon insertion for a Jehovah's Witness patient with situs inversus anomaly

We report the successful endovascular repair of a rare case of aortic rupture caused by axillary intra-aortic balloon pump (IABP) insertion failure. A 38-year-old Jehovah's Witness female with situs inversus totalis was referred to our hospital for acute decompensated heart failure. We placed an axillary IABP for circulatory support. However, an exchange was required due to balloon malfunction (kinked driveline). Unfortunately, the exchange was complicated by an iatrogenic aortic rupture along with a large hematoma compressing the trachea. Emergent endovascular repair was performed successfully without any blood transfusion. Postoperative computed tomography showed a successfully repaired aorta and resolving hematoma.