Autoimmune diseases are characterized by a breakdown of immune tolerance partly due to environmental factors. The short-chain fatty acid acetate, derived mostly from gut microbial fermentation of dietary fiber, promotes antiinflammatory Tregs and protects mice from type 1 diabetes, colitis, and allergies. Here, we show that the effects of acetate extend to another important immune subset involved in tolerance, the IL-10–producing regulatory B cells (B10 cells). Acetate directly promoted B10 cell differentiation from mouse B1a cells both in vivo and in vitro. These effects were linked to metabolic changes through the increased production of acetyl-coenzyme A, which fueled the TCA cycle and promoted posttranslational lysine acetylation. Acetate also promoted B10 cells from human blood cells through similar mechanisms. Finally, we identified that dietary fiber supplementation in healthy individuals was associated with increased blood-derived B10 cells. Direct delivery of acetate or indirect delivery via diets or bacteria that produce acetate might be a promising approach to restore B10 cells in noncommunicable diseases.

No abstract

Introduction Preoperative localization procedures of occult breast cancer (radioisotopic and wire localization) are invasive and uncomfortable. We have evaluated a novel technique which allows a virtual localization. Material and Methods Our retrospective study focused on patients treated for occult and unifocal breast cancer from September 2016 to June 2017. All patients had radioisotopic preoperative localization. We included patients who had a preoperative prone Magnetic Resonance Imaging (MRI) and an intraoperative 3D optical scan. During surgery, the surgeon localized the tumor thanks to a gamma detection probe and marked the localization on the skin with a black marker. The breast was then optically scanned. MRI was adjusted to the optical surface to match the exact breast position in the Operating Room. The virtual localization provided by the 3D breast modeling tool was retrospectively compared with the radioisotopic localization, defined as the pen mark visible in the optical scan. Results Nine patients were included in this feasibility study. Tumors were successfully localized in the respective breast quadrant. The mean cutaneous distance between virtual and radioisotopic localization was 1.4 cm in patients with low breast volume (5/9) and 2.8 cm in those with large breast volume (4/9). Conclusion We developed a research prototype which enables virtual preoperative localization of nonpalpable breast lesions using MRI images and intraoperative optical scanning. Parameter optimization is required and will lead to a precise and noninvasive tool. By adding augmented reality, it will be possible to initiate a prospective study to compare this tool with the traditional localizations.

No abstract

Funding informationMontpellier-Reine Breast Cancer Association.One third of operated breast cancers are clinically occult. 1 Nonpalpable breast cancers (NPBC) require accurate intraoperative guidance to achieve complete tumor removal. 1 Incomplete removal of lesions increases the rate of reexcision, worsening patient's discomfort, and cosmetic outcomes. 1 Localization techniques suffer from various limitations. Indocyanine green (ICG) fluorescence is commonly used for intraoperative identification of sentinel lymph nodes (SLN). 2 Its pertinence for NPBC is still underestimated.Darkness required in surgery room with available cameras has been a limitation for its use. We evaluated ICG method for NPBC localization, guided by a probe in ambient light, inspired by radioguided occult lesion localization (ROLL).We included ten patients scheduled for routine conserving surgery for NPBC, from October 2017 to July 2018 in our Breast Surgery Department. Nodular mass was assessed by mammography and ultra sound (US). Exclusion criteria were palpable tumor, advanced stage of disease requiring neo-adjuvant therapy, and hypersensitivity to iodine. Patients with bilateral tumor were randomized to evaluate this technique in one breast. Study was approved by Ethics Committee (NCT03313908). National Agency for Safety of Medicines (ANSM) authorized this clinical trial on medicinal product for human use (Reference: 170405A-13). Identifier on Clinical Trials. gov is NCT03313908. Written consent was signed after detailed written information. The day preceding surgery, injection of 0.2 mL (10 MBq) of 99mTc-labeled rhenium sulfide (Nanocis1, IBA molecular France) was performed by a radiologist as described in ROLL. 3 This injection is done the day before surgery to avoid delays in the operating room in case of difficulties in radiology or nuclear medicine departments. On the day of surgery, under general anesthesia, 0.2-0.8 mL (0.5-2 mg) of ICG was injected close to NPBC, by a radiologist under US guidance. Tumor was spotted by two methods: isotope and fluorescence. For isotope localization, common gamma probe (Gamma sud II/Clerad: GS 5002) with collimator was used, like classical ROLL. For fluorescence localization, we used new handheld dual-fluorescence probe (Europrobe 3, Eurorad SA) operating in ambient light, commercially available but mainly used for lymph node detection. Probes defined "hot spot'' in area of maximum radioactivity or fluorescence corresponding to the site of lesion. Localization of lesion was drawn on skin with marker pen for both methods (Figure 1). Distance between markers was measured. Surgeons performed conserving breast surgery following standard procedure, using ROLL. Primary end point was to determine reliability of ICG fluorescence in locating NPBC, estimated by distance between fluorescence hot spot and tumor localization on histologic specimen, compared to isotope hot spot, identified by wires (Figure 2). Secondary end points were distance between hot spot marks on skin, evaluation of technical feasibilit...