Identification of demyelinating lesions and application of McDonald criteria when confronted with white matter lesions on brain MRI.

INTRODUCTION: White matter lesions (WML) on magnetic resonance imaging (MRI) are common in clinical practice. When analyzing WML, radiologists sometimes propose a pathophysiological mechanism to explain the observed MRI abnormalities, which can be a source of anxiety for patients. In some cases, discordance may appear between the patient's clinical symptoms and the identification of the MRI-appearing WML, leading to extensive diagnostic work-up. To avoid misdiagnosis, the analysis of WML should be standardized, and a consensual MRI reading approach is needed. OBJECTIVE: To analyze the MRI WML identification process, associated diagnosis approach, and misinterpretations in physicians involved in WML routine practice. METHODS: Through a survey distributed online to practitioners involved in WML diagnostic work-up, we described the leading causes of MRI expertise misdiagnosis and associated factors: clinical experience, physicians' subspecialty and location of practice, and type of device used to complete the survey. The survey consisted of sixteen T2-weighted images MRI analysis, from which ten were guided (binary response to lesion location identification), four were not shown (multiple possible answers), and two were associated with dissemination in space (DIS) McDonald criteria application. Two independent, experienced practitioners determined the correct answers before the participants' completion. RESULTS: In total, 364 participants from the French Neuro Radiological (SFNR), French Neurological (SFN), and French Multiple Sclerosis (SFSEP) societies completed the survey entirely. According to lesion identification, 34.3% and 16.9% of the participants correctly identified juxtacortical and periventricular lesions, respectively, whereas 56.3% correctly identified non-guided lesions. Application of the 2017 McDonald's DIS criteria was correct for 35.3% of the participants. According to the global survey scoring, factors independently associated with correct answers in multivariate analysis were MS-expert subspecialty (P<0.001), young clinical practitioners (P=0.02), and the use of a computer instead of a smartphone to perform WML analysis (P=0.03). CONCLUSION: Our results highlight the difficulties regarding WML analysis in clinical practice and suggest that radiologists and neurologists should rely on each other to ensure the diagnosis of multiple sclerosis and related disorders and limit misdiagnoses.

Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

Aqua polo: Preliminary feasibility and efficacy study of a programme of adapted, supervised water polo to reduce fatigue and improve women's psychological and social recovery after breast cancer treatment: A mixed-methods design.

Physical activity has been shown to have many benefits, including reducing cancer-related fatigue (CRF) and improving psychological and physical recovery from breast cancer. Some authors have shown the benefits of aquatic practice, while others have detailed the benefits of group and supervised practice. We hypothesize that an innovative sports coaching proposal could allow a significant adherence of patients and contribute to their health improvement. The main objective is to study the feasibility of an adapted water polo programme (aqua polo) for women after breast cancer. Secondarily we will analyse the effect of such a practice on patients' recovery and study the relationship between coaches and participants. The use of mixed methods will allow us to question the underlying processes precisely. This is a prospective, non-randomized, monocentric study with a sample of 24 breast cancer patients after treatment. The intervention is a 20 week programme (1 session per week) of aqua polo in a swim club facility, supervised by professional water-polo coaches. The variables measured are patient participation, quality of life (QLQ BR23), CRF (R-PFS) and post-traumatic growth (PTG-I) as well as different variables to observe physical capacity (strength with dynamometer, step-test and arm amplitude). The quality of the coach-patient relationship will be evaluated (CART-Q) to explore its dynamics. Participatory observations and interviews will be carried out to report on the interactions between the coach and the participants during the sessions. Registration number and name of trial registry: No. EudraCT or ID-RCB: 2019-A03003-54 and NCT: NCT04235946.

Spontaneous immortalization of chicken fibroblasts generates stable, high-yield cell lines for serum-free production of cultured meat.

Cellular agriculture could meet growing demand for animal products, but yields are typically low and regulatory bodies restrict genetic modification for cultured meat production. Here we demonstrate the spontaneous immortalization and genetic stability of fibroblasts derived from several chicken breeds. Cell lines were adapted to grow as single-cell suspensions using serum-free culture medium, reaching densities of 108 × 106 cells per ml in continuous culture, corresponding to yields of 36% w/v. We show that lecithin activates peroxisome proliferator-activated receptor gamma (PPARγ), inducing adipogenesis in immortalized fibroblasts. Blending cultured adipocyte-like cells with extruded soy protein, formed chicken strips in which texture was supported by animal and plant proteins while aroma and flavour were driven by cultured animal fat. Visual and sensory analysis graded the product 4.5/5.0, with 85% of participants extremely likely to replace their food choice with this cultured meat product. Immortalization without genetic modification and high-yield manufacturing are critical for the market realization of cultured meat.

School-wide positive behavioral interventions and supports and students with extensive support needs: a scoping review.

School-wide Positive Behavioral Interventions and Supports (SWPBIS) is an inclusive multi-tiered system of behavioral supports that has been widely adopted by K-12 schools in the United States. SWPBIS focuses on creating safe, equitable, and inclusive school environments and has been linked to both positive behavioral and academic outcomes for students and improved perceptions of efficacy and job satisfaction for school personnel. However, there remain concerns about the involvement of students with extensive support needs (ESN) in SWPBIS despite calls to action in 2006 and 2016 for research in this area. Addressing these concerns, we conducted a scoping review to examine the current research literature on SWPBIS and students with ESN. We found that only 10 studies have been conducted since the 2006 call to action. Studies primarily focused on stakeholder perspectives regarding the importance or availability of SWPBIS for students with ESN. Although few studies examined SWPBIS effectiveness, findings from these studies lend support to the effectiveness of Tier 1 SWPBIS for students with ESN. We describe several key implications for supporting the inclusion of students with ESN in SWPBIS and future research initiatives.

De novo adamantinomatous craniopharyngioma with long-term pre-diagnostic imaging.

Adamantinomatous craniopharyngioma has a bimodal age distribution occurring in children aged 5-15 years and less frequently in adults aged 45-60 years. The current embryogenetic hypothesis suggests that adamantinomatous craniopharyngioma (ACP) arises from epithelial remnants of the craniopharyngeal duct or Rathke's pouch. It is thought that this tumor exists early on during childhood but remains indolent, growing very slowly until it is diagnosed incidentally or due to symptoms. Recent reports of de novo development of ACP, however, have challenged this theory. Herein, we present a case of an incidentally discovered de novo adamantinomatous craniopharyngioma that was documented to arise de novo on serial MRIs performed for a different indication. To our knowledge, this is the first report of a middle-aged patient who is diagnosed with a de novo ACP documented with contrast-enhanced MRIs of the sella over a 16-year period. This case challenges our current understanding of the pathophysiology of adamantinomatous craniopharyngioma.

Optic nerve sheath fenestration: Current status in France and comparison of 6 different surgical approaches.

PURPOSE: Optic nerve sheath fenestration (ONSF) is a surgical procedure commonly performed in the Anglo-Saxon countries for the treatment of medically refractory idiopathic intracranial hypertension (IIH). We chose to compare 6 different trans-orbital surgical approaches to ONSF. We also desired to determine the number of optic nerve decompression procedures performed in France in 2019 and 2020. METHODS: Four fresh frozen orbits were dissected at the University of Nice anatomy laboratory. We performed the following surgical approaches: (i) eyelid crease, (ii) lid-split, (iii) medial transconjunctival with medial rectus disinsertion, (iv) medial transconjunctival without rectus disinsertion, (v) lateral transconjunctival and (vi) lateral orbitotomy. For each surgical approach, we measured the distance between the incision and the optic nerve dura mater. We also extracted data from the French National PMSI (Programme de Médicalisation des Systèmes d' Information) database from January 2019 through December 2020 to determine the annual number of optic nerve decompression procedures. RESULTS: The lid crease and medial transconjunctival approaches provided the shortest distance to the optic nerve (average 21mm and 24mm, respectively) and the lowest levels of difficulty compared to the other surgical routes. A total of 23 and 45 optic nerve decompressions were performed in France in 2019 and 2020, respectively. Among them, only 2 and 7 procedures, respectively, were performed through a trans-orbital approach. CONCLUSION: Upper lid crease incision and medial transconjunctival approaches are the most direct and easiest surgical routes when performing an ONSF. We found that ONSF was rarely performed in France. We strongly recommend close cooperation between ophthalmologists, neurologists, neurosurgeons and interventional radiologists.

A 2-4 keV multilayer mirrored channel for the NIF Dante system.

During inertial confinement fusion experiments at the National Ignition Facility (NIF), a capsule filled with deuterium and tritium (DT) gas, surrounded by a DT ice layer and a high-density carbon ablator, is driven to the temperature and densities required to initiate fusion. In the indirect method, 2 MJ of NIF laser light heats the inside of a gold hohlraum to a radiation temperature of 300 eV; thermal x rays from the hohlraum interior couple to the capsule and create a central hotspot at tens of millions degrees Kelvin and a density of 100-200 g/cm3. During the laser interaction with the gold wall, m-band x rays are produced at ∼2.5 keV; these can penetrate into the capsule and preheat the ablator and DT fuel. Preheat can impact instability growth rates in the ablation front and at the fuel-ablator interface. Monitoring the hohlraum x-ray spectrum throughout the implosion is, therefore, critical; for this purpose, a Multilayer Mirror (MLM) with flat response in the 2-4 keV range has been installed in the NIF 37° Dante calorimeter. Precision engineering and x-ray calibration of components mean the channel will report 2-4 keV spectral power with an uncertainty of ±8.7%.

Improving access to affordable quality-assured inhaled medicines in low- and middle-income countries.

BACKGROUND: Access to affordable inhaled medicines for chronic respiratory diseases (CRDs) is severely limited in low- and middle-income countries (LMICs), causing avoidable morbidity and mortality. The International Union Against Tuberculosis and Lung Disease convened a stakeholder meeting on this topic in February 2022.METHODS: Focused group discussions were informed by literature and presentations summarising experiences of obtaining inhaled medicines in LMICs. The virtual meeting was moderated using a topic guide around barriers and solutions to improve access. The thematic framework approach was used for analysis.RESULTS: A total of 58 key stakeholders, including patients, healthcare practitioners, members of national and international organisations, industry and WHO representatives attended the meeting. There were 20 pre-meeting material submissions. The main barriers identified were 1) low awareness of CRDs; 2) limited data on CRD burden and treatments in LMICs; 3) ineffective procurement and distribution networks; and 4) poor communication of the needs of people with CRDs. Solutions discussed were 1) generation of data to inform policy and practice; 2) capacity building; 3) improved procurement mechanisms; 4) strengthened advocacy practices; and 5) a World Health Assembly Resolution.CONCLUSION: There are opportunities to achieve improved access to affordable, quality-assured inhaled medicines in LMICs through coordinated, multi-stakeholder, collaborative efforts.

Active Precipitation of Radiation Belt Electrons Using Rocket Exhaust Driven Amplification (REDA) of Man-Made Whistlers.

Ground-based very low frequency (VLF) transmitters located around the world generate signals that leak through the bottom side of the ionosphere in the form of whistler mode waves. Wave and particle measurements on satellites have observed that these man-made VLF waves can be strong enough to scatter trapped energetic electrons into low pitch angle orbits, causing loss by absorption in the lower atmosphere. This precipitation loss process is greatly enhanced by intentional amplification of the whistler waves using a newly discovered process called rocket exhaust driven amplification (REDA). Satellite measurements of REDA have shown between 30 and 50 dB intensification of VLF waves in space using a 60 s burn of the 150 g/s thruster on the Cygnus satellite that services the International Space Station. This controlled amplification process is adequate to deplete the energetic particle population on the affected field lines in a few minutes rather than the multi-day period it would take naturally. Numerical simulations of the pitch angle diffusion for radiation belt particles use the UCLA quasi-linear Fokker Planck model to assess the impact of REDA on radiation belt remediation of newly injected energetic electrons. The simulated precipitation fluxes of energetic electrons are applied to models of D-region electron density and bremsstrahlung X-rays for predictions of the modified environment that can be observed with satellite and ground-based sensors.

Changes in Surgical Pathology Case Volume and Amendment Rates During the COVID-19 Pandemic.

OBJECTIVES: Surgical pathology volume decreased during the peak of the coronavirus disease 2019 (COVID-19) pandemic. We looked at the 4 months with the greatest reduction in surgical pathology volume during the COVID-19 pandemic and compared them with those same months in 2019 to determine changes in specimen volume. We compared the amendment rates during those periods and types of amendments issued (identification [ID], report defect [RD], diagnostic information [DI]). METHODS: All pathology reports between March to June 2019 and March to June 2020 were extracted from the pathology information system. All amendments issued were extracted over the same period and then subclassified by two pathologists. RESULTS: There was a 52.1% reduction in surgical pathology volume between the 4-month periods in 2019 and 2020 (P = .04). The amendment rate was 0.9% in 2019 compared with 1.4% in 2020, representing a 65.5% increase in amendments overall. There was a 53.3% reduction in amendments issued for ID, a 3.8% reduction in RD, and a 23.2% increase in amendments issued for DI. The change in amendments was not statistically significant. CONCLUSIONS: These findings suggest that a reduction in workload would not improve error rates. The circumstances of the pandemic highlight the many factors contributing to error rates in surgical pathology.

Small intestine motility disorders: Chronic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction (CIPO) is a syndrome associating chronic or recurrent obstructive symptoms with intestinal dilation on imaging but without organic obstruction in the digestive tract. It is a rare disease with varying severity whose diagnosis is very complex. The diagnosis is based on clinical and paraclinical arguments in the context of repetitive occlusive syndromes when no mechanical obstruction of the digestive lumen is observed. Abdomino-pelvic computerized tomography (CT) must be performed to rule out a mechanical obstruction. An additional reference examination is trans-duodenal manometry of the small intestine, which is almost never normal in CIPO, but the test is rarely systematically performed. CIPO can be primary (acquired or congenital) or secondary to a systemic pathology (neurological, metabolic, etc.) resulting in neuromuscular damage to the intestinal tract. There are familial forms associated with genetic mutations. The majority of CIPO cases are idiopathic. Symptoms of the CIPO syndrome should be investigated with a complete assessment, guided by questioning and clinical examination that should also focus on urinary, neurological and cardiac involvement. Pathological tissue analysis is interesting for the etiological classification but is difficult to obtain. CIPO must be distinguished from non-CIPO intestinal dysmotility. Management must be carried out in an expert center with multidisciplinary care involving gastroenterologists, nutritionists, psychologists, radiologists, pathologists and digestive surgeons. It is essentially based on symptomatic management (especially with pro-kinetic agents and analgesics), nutritional support, as well as psychological support in view of its impact on quality of life. Surgical management is sometimes necessary.

[Surgery or not on an atypical breast lesion? Taking anxiety into account in shared decision support from a prospective cohort of 300 patients]. / Opérer ou non une lésion atypique du sein ? Prise en compte de l'anxiété dans l'aide à la décision partagée à partir d'une cohorte prospective de 300 patientes.

INTRODUCTION: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions (ABL)". Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. METHODS: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. RESULTS: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, P<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). CONCLUSION: Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.

The impact of routine pulse oximetry use on outcomes in COVID-19-infected patients at increased risk of severe disease: A retrospective cohort analysis.

BACKGROUND: The phenomenon of silent hypoxaemia has been described in patients with COVID-19 pneumonia, which is characterised by low oxygen saturation levels of <90% in those who appear clinically well and do not show signs of significant respiratory distress. OBJECTIVES: To assess the impact on clinical outcomes for high-risk COVID-19 patients using a pulse oximeter to monitor oxygen saturation levels in a home setting. METHODS: We performed a retrospective cohort analysis using data from a large South African insurance administrator. Patients were categorised as high risk, based on age and specific underlying clinical conditions, or from predictive models derived from medical scheme administrative claims data. The impact of pulse oximetry home monitoring on COVID-19 clinical outcomes was investigated by the use of Cox proportional hazard models. RESULTS: Between 2 March 2020 and 31 October 2020, of 38 660 patients analysed, 8 115 were in the intervention group. The 60-day mortality rate for the evaluated high-risk population was 1.35%. After adjusting for age and comorbidity differences, the intervention group was found to have an adjusted hazard ratio of 0.52 (p<0.0001). No statistical significance was found between the intervened and control groups for admission to hospital, admission to intensive care unit (ICU) and use of mechanical ventilation. The intervention group had a lower median C-reactive protein (CRP) level on admission (p=0.03). After adjustment for admission CRP levels, elevated CRP was associated with an increased mortality (p<0.0001), while the statistical significance in mortality between the intervention and the control group was lost. CONCLUSIONS: High-risk COVID-19 patients who used a pulse oximeter to monitor oxygen saturation levels had significantly lower mortality rates compared with other high-risk patients. The mortality benefit may be explained by earlier presentation to hospital, as suggested by lower initial CRP levels.

Lymphovascular invasion has a significant prognostic impact in patients with early breast cancer, results from a large, national, multicenter, retrospective cohort study.

BACKGROUND: We determined the prognostic impact of lymphovascular invasion (LVI) in a large, national, multicenter, retrospective cohort of patients with early breast cancer (BC) according to numerous factors. PATIENTS AND METHODS: We collected data on 17 322 early BC patients treated in 13 French cancer centers from 1991 to 2013. Survival functions were calculated using the Kaplan-Meier method and multivariate survival analyses were carried out using the Cox proportional hazards regression model adjusted for significant variables associated with LVI or not. Two propensity score-based matching approaches were used to balance differences in known prognostic variables associated with LVI status and to assess the impact of adjuvant chemotherapy (AC) in LVI-positive luminal A-like patients. RESULTS: LVI was present in 24.3% (4205) of patients. LVI was significantly and independently associated with all clinical and pathological characteristics analyzed in the entire population and according to endocrine receptor (ER) status except for the time period in binary logistic regression. According to multivariate analyses including ER status, AC, grade, and tumor subtypes, the presence of LVI was significantly associated with a negative prognostic impact on overall (OS), disease-free (DFS), and metastasis-free survival (MFS) in all patients [hazard ratio (HR) = 1.345, HR = 1.312, and HR = 1.415, respectively; P < 0.0001], which was also observed in the propensity score-based analysis in addition to the association of AC with a significant increase in both OS and DFS in LVI-positive luminal A-like patients. LVI did not have a significant impact in either patients with ER-positive grade 3 tumors or those with AC-treated luminal A-like tumors. CONCLUSION: The presence of LVI has an independent negative prognostic impact on OS, DFS, and MFS in early BC patients, except in ER-positive grade 3 tumors and in those with luminal A-like tumors treated with AC. Therefore, LVI may indicate the existence of a subset of luminal A-like patients who may still benefit from adjuvant therapy.

Atypical facial presentation of subcutaneous fat necrosis of the newborn.

Subcutaneous fat necrosis of the newborn (SCFN) is a rare self-limiting panniculitis. It is thought to be associated with perinatal hypoxia and therapeutic hypothermia. It is characterised by firm subcutaneous nodules on the back, shoulder and arms. We present a rare facial presentation of SCFN in a 4-week-old infant with no history of therapeutic cooling. She presented with a discrete right cheek mass with no overlying skin changes. We present the diagnostic challenge and undertake a review of the literature. SCFN is an important differential diagnosis in a neonate with subcutaneous facial lesions. SCFN can be complicated by metabolic derangements including hypercalcaemia.

Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort☆.

BACKGROUND: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm. PATIENTS AND METHODS: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i-), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status. RESULTS: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS. CONCLUSION: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0.