[Can we avoid axillary lymph node dissection in patients with node positive invasive breast carcinoma?] / Peut-on surseoir au curage axillaire en cas de carcinome mammaire invasif avec envahissement ganglionnaire ?

OBJECTIVES: The indications and modalities of breast and axillary surgery are undergoing profound change, with the aim of personalizing surgical management while avoiding over-treatment. To update best practices for axillary surgery, four questions were selected by the Senology Commission of the Collège National des Gynécologues et Obstétriciens Français (CNGOF), focusing on, firstly, the definition and evaluation of targeted axillary dissection (TAD) techniques; secondly, the possibility of surgical de-escalation in case of initial lymph node involvement while performing initial surgery; thirdly, in case of surgery following neo-adjuvant systemic therapy (NAST), and fourthly, contra-indications to de-escalation of axillary surgery to allow access to particular adjuvant systemic therapies. METHODS: The Senology Commission based its responses primarily on an analysis of the international literature, clinical practice recommendations and national and international guidelines. RESULTS: Firstly, TAD is a technique that combines excision of clipped metastatic axillary node(s) and the axillary sentinel lymph nodes (ASLNs). The detection rate and sensitivity are increased but it still needs to be standardized and practices better evaluated. Secondly, TAD represents an alternative to axillary clearance in cases of metastatic involvement of a single node that can be resected. Thirdly, neither TAD nor ASLN alone is recommended in France after NAST outside of clinical trials, although it is used in several countries in cases of complete pathological response in the lymph nodes, and when at least three lymph nodes have been removed. Fourthly, as some adjuvant targeted therapies are indicated in cases of lymph node invasion of more than three lymph nodes, the place of TAD in this context remains to be defined. CONCLUSION: Axillary surgical de-escalation can limit the morbidity of axillary clearance. Having proved that TAD does not reduce patient survival, it will most probably replace axillary clearance in well-defined indications. This will require prior standardization of the method and its indications and contra-indications, particularly to enable the use of new targeted therapies.

[Updated surgical indications and quality and safety indicators in the management of infiltrative breast carcinoma]. / Actualisation des indications chirurgicales et des indicateurs de qualité et sécurité des soins dans la prise en charge des carcinomes mammaires invasifs.

OBJECTIVES: Breast surgery is the cornerstone of breast cancer treatment. Its indications and procedures are constantly evolving. To update best practices, four questions were submitted to the Senology Commission (SC) of the Collège national des gynécologues et obstétriciens français (CNGOF), covering the indications and modalities of tumor surgery: (1) initially, (2) following neoadjuvant systemic treatment, (3) in case of local recurrence, and (4) the quality and safety of care indicators applicable to this surgery. METHODS: The CNGOF SC essentially based its responses on the clinical practice recommendations and guidelines of the French Cancer Institute concerning invasive carcinomas of the breast. Exclusion criteria were carcinoma in situ, sarcoma and axillary surgery. RESULTS: To define the type of breast surgery, knowledge of four parameters is essential: the patient's level of risk, the presence of metastases, the size of the breast tumor and its focality (assessed by the clinical/mammography/ultrasound tripod). (1) In the case of initial management, the 6 indications for mastectomy are patient choice (particularly in case of high risk), contraindication to radiotherapy, inflammatory cancer (T4d), surgery with positive margins (after several surgical intervention), surgery that cannot be performed as a monobloc in the case of tumors with multiple foci, and poor expected aesthetic results. All other situations should be treated conservatively. (2) The same criteria apply after neoadjuvant systemic treatment, with conservative treatment still possible whatever the size (excluding carcinomatous mastitis) and focality of the initial tumor. (3) In case of local recurrence, total mastectomy is the reference treatment, with a second conservative treatment reserved for patients with no risk factors for a second recurrence, and no poor prognostic factors, after validation in a multidisciplinary meeting. (4) Four quality and safety indicators apply to breast surgery: it must be performed after obtaining a histological diagnosis, within less than 6 weeks of mammography, in a single surgery in over 80% of cases, and followed by local radiotherapy in the case of conservative treatment. CONCLUSION: The indications and modalities of breast surgery are evolving rapidly. To improve aesthetic results, oncoplastic techniques, immediate breast reconstruction, and preservation of the skin or nipple-areolar complex need to be further developed and evaluated in the long-term. These developments must necessarily be accompanied in France by a training policy for breast surgeons.

Evaluation of Cardiac Substructures Exposure of DIBH-3DCRT, FB-HT, and FB-3DCRT in Hypofractionated Radiotherapy for Left-Sided Breast Cancer after Breast-Conserving Surgery: An In Silico Planning Study.

Left-sided breast cancer radiotherapy can lead to late cardiovascular complications, including ischemic events. To mitigate these risks, cardiac-sparing techniques such as deep-inspiration breath-hold (DIBH) and intensity-modulated radiotherapy (IMRT) have been developed. However, recent studies have shown that mean heart dose is not a sufficient dosimetric parameter for assessing cardiac exposure. In this study, we aimed to compare the radiation exposure to cardiac substructures for ten patients who underwent hypofractionated radiotherapy using DIBH three-dimensional conformal radiation therapy (3DCRT), free-breathing (FB)-3DCRT, and FB helical tomotherapy (HT). Dosimetric parameters of cardiac substructures were analyzed, and the results were statistically compared using the Wilcoxon signed-rank test. This study found a significant reduction in the dose to the heart, left anterior descending coronary artery, and ventricles with DIBH-3DCRT and FB-HT compared to FB-3DCRT. While DIBH-3DCRT was very effective in sparing the heart, in some cases, it provided little or no cardiac sparing. FB-HT can be an interesting treatment modality to reduce the dose to major coronary vessels and ventricles and may be of interest for patients with cardiovascular risks who do not benefit from or cannot perform DIBH. These findings highlight the importance of cardiac-sparing techniques for precise delivery of radiation therapy.

Efficacity of Deep Inspiration Breath Hold and Intensity-Modulated Radiotherapy in Preventing Perfusion Defect for Left Sided Breast Cancer (EDIPE): A Prospective Cohort Study Protocol.

Breast radiotherapy can lead to radiation-induced cardiac disease, particularly in left breast cancers. Recent studies have shown that subclinical cardiac lesions, such as myocardial perfusion deficits, may occur early after radiotherapy. The primary method for irradiating breast cancer, known as opposite tangential field radiotherapy, can cause the anterior interventricular coronary artery to receive a high dose of radiation during left breast irradiation. To explore alternative approaches that could reduce the risk of myocardial perfusion defects in patients with left breast cancer, we plan to conduct a prospective single-center study using a combination of deep inspiration breath hold radiotherapy and intensity modulated radiation therapy. The study will use stress and, if necessary, resting myocardial scintigraphy to assess myocardial perfusion. The trial aims to show that reducing the cardiac dose with these techniques can prevent the appearance of early (3-month) and medium-term (6- and 12-month) perfusion disorders.

Distended Seminal Vesicles Are Involved in Specific Cerebral Sexual Arousal: A Pilot Study Using Functional Brain Imaging in Young Healthy Men.

Background: Whether seminal vesicles play a role in sexual activity in men is unknown. No study so far has compared the neural processing of visual sexual stimuli in men depending on the filling state of the seminal vesicles. Objective: To evaluate potential specific cortical activation by visual sexual stimuli with distended and empty seminal vesicles. Design setting and participants: A prospective case-control trial was conducted. Six male individuals underwent two visits on 2 consecutive days for hormone analyses; Derogatis Interview for Sexual Functioning (DISF) questionnaire; functional magnetic resonance imaging (fMRI) with passively viewing sexual, neutral, positive, and negative emotional pictures; and structural pelvic MRI. After the first visit, the participants had to empty seminal vesicles by masturbation. During fMRI, every participant viewed alternating blocks of sexual, neutral, positive, and negative emotional pictures. Outcome measurements and statistical analysis: Comparisons between days 1 and 2 were evaluated using paired t tests. Results and limitations: No significant differences were observed regarding hormone analyses, DISF questionnaire score, and arousal scoring between days 1 and 2. Seminal vesicle volume was significantly lower on day 2 (p = 0.003). Significantly higher activation was observed in the right precentral gyrus, middle frontal gyrus, and right superior temporal sulcus when contrasted for sexual over neutral (p < 0.05). Conclusions: In response to pictures with sexual emotional content, significantly higher activation was detected in brain areas involved in motor preparation (arousal) and coding of desirability of visual sexual stimuli in men with distended seminal vesicles than in the same men with emptied seminal vesicles. This suggests that the filling state of the seminal vesicles may influence sexual desire in men. Patient summary: We compared brain activity of men with filled and emptied seminal vesicles by functional magnetic resonance imaging. We found that men with filled seminal vesicles had higher activation of brain areas involved in arousal and sexual desire.

Adjuvant hypofractionated radiotherapy with simultaneous integrated boost after breast-conserving surgery: A systematic literature review.

PURPOSES: Several studies have shown that simultaneous integrated boost provides better dose homogeneity, improves the biologically effective dose-volume histogram and reduces treatment time compared to sequential boost in breast cancer. PATIENTS AND METHODS: We conducted a systematic review of published trials evaluating simultaneous integrated boost in hypofractionated radiotherapy to analyze the results in terms of overall survival, local control, early and late side effects, and radiotherapy techniques used. RESULTS: Upon 9 articles, the prescribed dose to the whole breast varied from 40 to 46.8 Gy. The number of fractions varies from 15 to 20 fractions. The prescribed dose per fraction to the boost varied from 2.4 Gy per fraction to 3.4 Gy per fraction for a total boost dose from 48 to 52.8 Gy. CONCLUSIONS: Simultaneous integrated boost seems effective and safe when given hypofractionated whole-breast irradiation but needs to be validated in prospective trials.

Evaluation of Microscopic Tumour Extension in Localized Stage Non-Small-Cell Lung Cancer for Stereotactic Radiotherapy Planning.

Background: Stereotactic radiotherapy for localised stage non-small-cell lung carcinoma (NSCLC) is an alternative indication for patients who are inoperable or refuse surgery. A study showed that the microscopic tumour extension (ME) of NSCLC varied according to the histological type, which allowed us to deduce adapted margins for the clinical target volume (CTV). However, to date, no study has been able to define the most relevant margins for patients with stage 1 tumours. Methods: We performed a retrospective analysis including patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) of localised stage T1N0 or T2aN0 who underwent surgery. The ME was measured from this boundary. The profile of the type of tumour spread was also evaluated. Results: The margin required to cover the ME of a localised NSCLC with a 95% probability is 4.4 mm and 2.9 mm for SCC and ADC, respectively. A significant difference in the maximum distance of the ME between the tumour-infiltrating lymphocytes (TILs), 0−10% and 50−90% (p < 0.05), was noted for SCC. There was a significant difference in the maximum ME distance based on whether the patient had chronic obstructive pulmonary disease (COPD) (p = 0.011) for ADC. Multivariate analysis showed a statistically significant relationship between the maximum microextension distance and size with the shrinkage coefficient. Conclusion: This study definitively demonstrated that the ME depends on the pathology subtype of NSCLC. According to International Commission on Radiation Units and Measurements (ICRU) reports, 50, 62 and 83 CTV margins, proposed by these results, should be added to the GTV (Gross tumour volume). When stereotactic body radiation therapy is used, this approach should be considered in conjunction with the dataset and other margins to be applied.

The Impact of an Incidental Dose on Axillary Tumor Control and Toxicity in Localized Breast Cancer: A Retrospective Analysis.

PURPOSE: The dosimetric analysis of the incidental axillary dose delivered to axillary lymph node levels I-III by different techniques of whole breast irradiation and the analysis of prognostic factors of axillary recurrence of breast cancer. METHODS: We perform a retrospective analysis that includes 171 patients with localized breast carcinoma irradiated at Centre Paul Strauss. To be included in the study, patients had to have a histological confirmation of breast cancer diagnosis, surgical treatment without axillary lymph node dissection (ALND), whole breast irradiation without axillary irradiation by a specific field, and a treatment plan available. RESULTS: Three patients had lymph node recurrence. There was no significant correlation between the maximal or mean dose delivered at the three axillary levels and the risk of axillary lymph node recurrence. There was no significant correlation between the irradiation technique and the risk of axillary lymph node recurrence. Two patients, both in the HT group, had lymphoedema. There was significantly more lymphoedema in the HT group than in the ST and IMRT groups (p < 0.048). The mean dose in level II was significantly higher in the group of patients with lymphoedema (3.45 Gy (1.08; 9.62) vs. 23.4 Gy (23.1; 23.6)) (p < 0.02). CONCLUSION: The irradiation technique has an influence on the incidental dose delivered to the axillary area, but has no influence on the risk of axillary recurrence. The risk of lymphoedema could be related to the use of HT and the mean dose delivered at level II.

Should the management of radiation therapy for breast cancer be standardized? Results of a survey on current French practices in breast radiotherapy.

BACKGROUND: Breast cancer is the most frequent cancer in women in France. Its management has evolved considerably in recent years with a focus on reducing iatrogenic toxicity. The radiotherapy indications are validated in multidisciplinary consultation meetings; however, questions remain outstanding, particularly regarding hypofractionated radiotherapy, partial breast irradiation, and irradiation of the internal mammary chain and axillary lymph node area. MATERIALS AND METHODS: An online survey was sent to 47 heads of radiotherapy departments in France. The survey consisted of 22 questions concerning indications for irradiation of the supraclavicular, internal mammary and axillary lymph node areas; irradiation techniques and modalities; prescribed doses; and fractionation. RESULTS: Twenty-four out of 47 centers responded (response rate of 51%). This survey demonstrated a wide variation in the prescribed dose regimen, monoisocentric radiotherapy, and indications of irradiation of the lymph node areas. CONCLUSION: This survey provides insight into the current radiotherapy practice for breast cancer in France. It shows the need to standardize practices.

Incidental axillary dose delivery to axillary lymph node levels I-III by different techniques of whole-breast irradiation: a systematic literature review.

BACKGROUND AND OBJECTIVE: In breast cancer treatment, radiotherapy is an essential component for locoregional management. Axillary recurrence in patients with invasive breast carcinoma remains an issue. The question of whether breast irradiation may unintentionally include levels I, II, and III, and may decrease the risk of axillary recurrence, remains a topic of discussion. PATIENTS AND METHODS: A literature search was performed in PubMed and the Cochrane Library to identify articles that have published data regarding dose-volume analysis of axillary levels in breast irradiation. The following MESH terms were used: "breast cancer/lymph nodes" AND "radiotherapy dosage." RESULTS: Thirteen articles were identified. The irradiation technique, initial dose prescribed to the breast, delineated volumes, and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using standard fields (ST) ranged between 22 and 43.5 Gy, 3 and 35.6 Gy, and 1.0 and 20.5 Gy, respectively. The average doses delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using "high tangential" fields (HT) ranged between 38 and 49.7 Gy, 11 and 47.1 Gy, and 5 and 44.7 Gy, respectively. Finally, the average doses delivered to axilla levels I, II, and III using intensity-modulated radiation therapy (IMRT) were between 14.5 and 42.6 Gy, 3.4 and 35 Gy, and 1.2 and 25.5 Gy, respectively. CONCLUSION: Our literature review suggests that the incidental dose delivered to the axilla during whole-breast irradiation is heterogenous and dependent on the irradiation technique used. However, whether this observation can be translated into a therapeutic effect is still a matter of debate.

Indirect chiral magnetic exchange through Dzyaloshinskii-Moriya-enhanced RKKY interactions in manganese oxide chains on Ir(100).

Localized electron spins can couple magnetically via the Ruderman-Kittel-Kasuya-Yosida interaction even if their wave functions lack direct overlap. Theory predicts that spin-orbit scattering leads to a Dzyaloshinskii-Moriya type enhancement of this indirect exchange interaction, giving rise to chiral exchange terms. Here we present a combined spin-polarized scanning tunneling microscopy, angle-resolved photoemission, and density functional theory study of MnO2 chains on Ir(100). Whereas we find antiferromagnetic Mn-Mn coupling along the chain, the inter-chain coupling across the non-magnetic Ir substrate turns out to be chiral with a 120° rotation between adjacent MnO2 chains. Calculations reveal that the Dzyaloshinskii-Moriya interaction results in spin spirals with a periodicity in agreement with experiment. Our findings confirm the existence of indirect chiral magnetic exchange, potentially giving rise to exotic phenomena, such as chiral spin-liquid states in spin ice systems or the emergence of new quasiparticles.

Correction: LSD1 inhibition by tranylcypromine derivatives interferes with GFI1-mediated repression of PU.1 target genes and induces differentiation in AML.

The original version of this Article contained an error in the Acknowledgements section.

LSD1 inhibition by tranylcypromine derivatives interferes with GFI1-mediated repression of PU.1 target genes and induces differentiation in AML.

LSD1 has emerged as a promising epigenetic target in the treatment of acute myeloid leukemia (AML). We used two murine AML models based on retroviral overexpression of Hoxa9/Meis1 (H9M) or MN1 to study LSD1 loss of function in AML. The conditional knockout of Lsd1 resulted in differentiation with both granulocytic and monocytic features and increased ATRA sensitivity and extended the survival of mice with H9M-driven AML. The conditional knockout led to an increased expression of multiple genes regulated by the important myeloid transcription factors GFI1 and PU.1. These include the transcription factors GFI1B and IRF8. We also compared the effect of different irreversible and reversible inhibitors of LSD1 in AML and could show that only tranylcypromine derivatives were capable of inducing a differentiation response. We employed a conditional knock-in model of inactive, mutant LSD1 to study the effect of only interfering with LSD1 enzymatic activity. While this was sufficient to initiate differentiation, it did not result in a survival benefit in mice. Hence, we believe that targeting both enzymatic and scaffolding functions of LSD1 is required to efficiently treat AML. This finding as well as the identified biomarkers may be relevant for the treatment of AML patients with LSD1 inhibitors.

Magnetic Ground State Stabilized by Three-Site Interactions: Fe/Rh(111).

We report the direct observation of a theoretically predicted magnetic ground state in a monolayer Fe on Rh(111), which is referred to as an up-up-down-down (↑↑↓↓) double-row-wise antiferromagnetic spin structure, using spin-polarized scanning tunneling microscopy. This exotic phase, which exists in three orientational domains, is revealed by experiments with magnetic probe tips performed in external magnetic fields. It is shown that a hitherto unconsidered four-spin-three-site beyond-Heisenberg interaction distinctly contributes to the spin coupling of atoms with S≥1 spins. The observation of the ↑↑↓↓ order substantiates the presence of higher-order, in particular, three-site interactions, in thin magnetic films of itinerant magnets.

High-Pressure Synthesis and Characterization of the Ammonium Yttrium Borate (NH4)YB8O14.

The first high-pressure yttrium borate (NH4)YB8O14 was synthesized at 12.8 GPa/1300 °C using a Walker-type multianvil module. The compound crystallizes in the orthorhombic space group Pnma (no. 62) with the lattice parameters a = 17.6375(9), b = 10.7160(5), and c = 4.2191(2) Å. (NH4)YB8O14 constitutes a novel structure type but exhibits similarities to the crystal structure of ß-BaB4O7. X-ray single-crystal and powder diffraction, EDX, vibrational spectroscopy as well as quantum chemical calculations were used to characterize (NH4)YB8O14.

CD27 co-stimulation increases the abundance of regulatory T cells and reduces atherosclerosis in hyperlipidaemic mice.

Aims: The co-stimulatory receptor CD27 modulates responses of T cells, B cells, and NK cells. Various T cell subsets participate in atherogenesis. However, the role of CD27 in atherosclerosis remains unexplored. Methods and results: Here we investigated the effect of bone marrow-derived and systemic CD27 deficiency in Apolipoprotein E-deficient (Apoe-/-) mice in early and advanced stages of atherosclerosis. Lethally-irradiated Apoe-/- mice reconstituted with Cd27-/-Apoe-/- bone marrow and consuming an atherogenic diet displayed a markedly increased plaque size and lesional inflammation compared to mice receiving Cd27+/+Apoe-/- bone marrow. Accordingly, chow diet-fed Cd27-/-Apoe-/- mice showed exacerbated lesion development and increased inflammation at the age of 18 weeks. At a more advanced stage of atherosclerosis (28 weeks), lesion size and phenotype did not differ between the two groups. Systemic and bone marrow-derived CD27 deficiency reduced the abundance of regulatory T cells (Treg) in blood, lymphoid organs, and the aorta. Numbers of other immune cells were not affected while expression of inflammatory cytokine genes (e.g. IL-1ß and IL-6) was increased in the aorta when haematopoietic CD27 was lacking. In vitro, Tregs of CD27-deficient mice showed similar suppressive capacity compared with their wild-type controls and migrated equally towards CCL19 and CCL21. However, thymic Cd27-/- Tregs underwent increased apoptosis and expressed fewer markers of proliferation in vivo. Reconstitution of Cd27-/-Apoe-/- mice with Cd27+/+Apoe-/- Tregs reversed the increase in atherosclerosis. Conclusion: We demonstrate that CD27 co-stimulation increases the number of Tregs and limits lesion development and inflammation in experimental atherosclerosis, particularly during early stages of disease. Thus, our study suggests that promotion of CD27 function may mitigate atherosclerosis.

Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation.

Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting.

Mo2 B4 O9 -Connecting Borate and Metal-Cluster Chemistry.

We report on the first thoroughly characterized molybdenum borate, which was synthesized in a high-pressure/high-temperature experiment at 12.3 GPa/1300 °C using a Walker-type multianvil apparatus. Mo2 B4 O9 incorporates tetrahedral molybdenum clusters into an anionic borate crystal structure-a structural motif that has never been observed before in the wide field of borate crystal chemistry. The six bonding molecular orbitals of the [Mo4 ] tetrahedron are completely filled with 12 electrons, which are fully delocalized over the four molybdenum atoms. This finding is in agreement with the results of the magnetic measurements, which confirmed the diamagnetic character of Mo2 B4 O9 . The two four-coordinated boron sites can be differentiated in the 11 B MAS-NMR spectrum because of the strongly different degrees of local distortions. Experimentally obtained IR and Raman bands were assigned to vibrational modes based on DFT calculations.

Synthesis and Characterization of the High-Pressure Nickel Borate γ-NiB4O7.

γ-NiB4O7 was synthesized in a high-pressure/high-temperature experiment at 5 GPa and 900 °C. The single-crystal structure analysis yielded the following results: space group P6522 (No. 179), a = 425.6(2), c = 3490.5(2) pm, V = 0.5475(2) nm3, Z = 6, and Flack parameter x = -0.010(5). Second harmonic generation measurements confirmed the acentric crystal structure. Furthermore, γ-NiB4O7 was characterized via vibrational as well as single-crystal electronic absorption spectroscopy, magnetic measurements, high-temperature X-ray diffraction, differential scanning calorimetry, and thermogravimetry. Density functional theory-based calculations were performed to facilitate band assignments to vibrational modes and to evaluate the elastic properties and phase stability of γ-NiB4O7.

Deletion of junctional adhesion molecule A from platelets increases early-stage neointima formation after wire injury in hyperlipidemic mice.

Platelets play an important role in the pathogenesis of vascular remodelling after injury. Junctional adhesion molecule A (JAM-A) was recently described to regulate platelet activation. Specific deletion of JAM-A from platelets resulted in increased reactivity and in accelerated progression of atherosclerosis. The aim of this study was to investigate the specific contribution of platelet-derived JAM-A to neointima formation after vascular injury. Mice with or without platelet-specific (tr)JAM-A-deficiency in an apolipoprotein e (apoe-/- ) background underwent wire-induced injury of the common carotid artery. Ex vivo imaging by two-photon microscopy revealed increased platelet coverage at the site of injury in trJAM-A-deficient mice. Cell recruitment assays showed increased adhesion of monocytic cells to activated JAM-A-deficient platelets than to control platelets. Inhibition of αM ß2 or GPIbα, but not of CD62P, suppressed those differences. Up to 4 weeks after wire injury, intimal neoplasia and neointimal cellular content were analysed. Neointimal lesion area was increased in trJAM-A-/- apoe-/- mice and the lesions showed an increased macrophage accumulation and proliferating smooth muscle cells compared with trJAM-A+/+ apoe-/- littermates 2 weeks, but not 4 weeks after injury. Re-endothelialization was decreased in trJAM-A-/- apoe-/- mice compared with controls 2 weeks after injury, yet it was complete in both groups after 4 weeks. A platelet gain of function by deletion of JAM-A accelerates neointima formation only during earlier phases after vascular injury, through an increased recruitment of mononuclear cells. Thus, the contribution of platelets might become less important when neointima formation progresses to later stages.