Plasma levels of the proangiogenic protein CXCL16 remains elevated for 1 month after minimally invasive colorectal cancer resection

Abstract Background Inflammation-induced endothelial precursor cell recruitment and angiogenesis are thought to be associated with CXCL16-CXCR6 pair activity. This study’s main purpose was to determine plasma CXCL16 levels after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC); an adjunct study assessed wound fluid (WF) and plasma CXCL16 levels in a separate group of CRC patients. Methods CRC patients who had MICR and for whom plasma was available in a tissue bank were eligible. Plasma samples were collected preoperatively from all patients. Samples were also collected on postoperative days (POD) 1 and 3 and at various late postoperative time points (POD 7–34). In a separate study, blood and intra-abdominal wound fluid (WF) samples were collected from CRC MICR patients (pts). Samples were stored at − 80 °C. CXCL16 levels were determined via ELISA. The Wilcoxon signed-rank and Mann and Whitney tests were used for analysis. Results Main study: 86 CRC pts. were included. The mean preoperative plasma CXCL16 level was 2.36 ± 0.57 ng/ml. Elevated mean plasma levels (p <  0.0001 × first 4 time points) were noted on POD 1 (2.82 ± 0.81, n = 86), POD 3 (3.12 ± 0.77, n = 82), POD 7–13 (3.28 ± 0.88, n = 64), POD 14–20 (3.03 ± 0.62, n = 24), POD 21–27 (3.06 ± 0.67, n = 20, p = 0.0003), and POD 28–34 (3.17 ± 0.43, n = 11, p = 0.001) vs. preop levels. WF study: In the adjunct study, plasma and WF CXCL16 levels were determined for 23 CRC MICR pts. WF levels at all time points were significantly elevated over plasma levels. Conclusion Plasma CXCL16 levels were elevated for 4 weeks after minimally invasive colorectal resection for cancer. Also, WF CXCL16 levels were 3–10 times greater than the corresponding plasma concentrations. The source of the late plasma elevations may be the healing wound. Increased plasma CXCL16 levels may promote tumor angiogenesis in the first month after MICR

Minimally invasive liver resection to obtain tumor-infiltrating lymphocytes for adoptive cell therapy in patients with metastatic melanoma

<p>Abstract</p> <p>Background</p> <p>Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma has been reported to have a 56% overall response rate with 20% complete responders. To increase the availability of this promising therapy in patients with advanced melanoma, a minimally invasive approach to procure tumor for TIL generation is warranted.</p> <p>Methods</p> <p>A feasibility study was performed to determine the safety and efficacy of laparoscopic liver resection to generate TIL for ACT. Retrospective review of a prospectively maintained database identified 22 patients with advanced melanoma and visceral metastasis (AJCC Stage M1c) who underwent laparoscopic liver resection between 1 October 2005 and 31 July 2011. The indication for resection in all patients was to receive postoperative ACT with TIL.</p> <p>Results</p> <p>Twenty patients (91%) underwent resection utilizing a closed laparoscopic technique, one required hand-assistance and another required conversion to open resection. Median intraoperative blood loss was 100 mL with most cases performed without a Pringle maneuver. Median hospital stay was 3 days. Three (14%) patients experienced a complication from resection with no mortality. TIL were generated from 18 of 22 (82%) patients. Twelve of 15 (80%) TIL tested were found to have <it>in vitro</it> tumor reactivity. Eleven patients (50%) received the intended ACT. Two patients were rendered no evidence of disease after surgical resection, with one undergoing delayed ACT with generated TIL after relapse. Objective tumor response was seen in 5 of 11 patients (45%) who received TIL, with one patient experiencing an ongoing complete response (32+ months).</p> <p>Conclusions</p> <p>Laparoscopic liver resection can be performed with minimal morbidity and serve as an effective means to procure tumor to generate therapeutic TIL for ACT to patients with metastatic melanoma.</p

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health