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This study aimed to identify perioperative risk factors of acute kidney injury after heart transplantation and to evaluate 1-year clinical outcomes. A retrospective single-center cohort study. At a university hospital. All patients who underwent heart transplantation from January 2015 to December 2020. None. The authors recorded acute kidney injury after heart transplantation. One-year mortality and renal function also were recorded. Risk factors of acute kidney injury were evaluated using a multivariate logistic regression model. Long-term survival was compared between patients developing acute kidney injury and those who did not, using a log-rank test. Among 209 patients included in this study, 134 patients (64% [95% CI (58; 71)]) developed posttransplantation acute kidney injury. Factors independently associated with acute kidney injury were high body mass index (odds ratio [OR]: 1.18 [1.02-1.38] per kg/m2; p = 0.030), prolonged duration of cold ischemic period (OR: 1.11 [1.01-1.24] per 10 minutes; p = 0.039), and high dose of intraoperative dobutamine support (OR: 1.24 [1.06-1.46] per µg/kg/min; p = 0.008). At 1 year, patients who developed postoperative acute kidney injury had higher mortality rates (20% v 8%, p = 0.015). Among 172 survivors at 1 year, 82 survivors (48%) had worsened their renal function compared with preheart transplantation. This study highlighted the high incidence of acute kidney injury after heart transplantation and its impact on patient outcomes. Risk factors such as body mass index, prolonged cold ischemic period duration, and level of inotropic support with dobutamine were identified, providing insights for preventive strategies. [ABSTRACT FROM AUTHOR]

Besides their development as additional adjuvant treatments, CDK4/6 inhibitors combined with endocrine therapy could represent less toxic alternatives to chemotherapy in postmenopausal women with high-risk oestrogen receptor-positive, HER2-negative breast cancer currently a candidate for chemotherapy. The multicentre, international, randomised phase 2 NEOPAL trial showed that the letrozole-palbociclib combination led to clinical and pathological responses equivalent to sequential anthracycline-taxanes chemotherapy. Secondary objectives included survival outcomes. Secondary end-points of NEOPAL included progression-free survival (PFS) and invasive-disease free survival (iDFS) in the intent-to-treat population. Exploratory end-points were overall survival (OS) and breast cancer specific survival (BCSS) in the intent-to-treat population, as well as iDFS, OS and BCSS according to the administration of chemotherapy. Hundred and six patients were randomised. Pathological complete response rates were 3.8% and 5.9%. Twenty-three of the 53 patients in the letrozole-palbociclib arm received postoperative adjuvant chemotherapy. At a median follow-up of 40.4 months [0–56.6], 11 progressions have been observed, of which three were in the letrozole-palbociclib and 8 in the control arm. PFS (HR = 1.01; [95%CI 0.36–2.90], p = 0.98) and iDFS (HR = 0.83; [95%CI 0.31–2.23], p = 0.71) did not differ between both arms. The 40 months PFS rate was 86.7% [95%CI 78.0–96.4] and 89.9% [95%CI 81.8–98.7] in letrozole-palbociclib and control arms, respectively. Outcomes of patients who did not receive chemotherapy were not statistically different from those who received it. NEOPAL suggests that a neoadjuvant letrozole-palbociclib strategy may allow sparing chemotherapy in some patients with luminal breast cancer while allowing good long-term outcomes. Larger confirmatory studies are needed. [Display omitted] • First CDK4/6 neoadjuvant randomised trial to report survival outcomes. • NEOPAL trial compared neoadjuvant Letrozole Palbociclib versus chemotherapy. • Pathological complete response rates were identically low (3.8% and 5.9%, respectively). • Progression-free survival (HR = 1.01; [95%CI 0.36–2.90], p = 0.98) did not differ between both arms. • Invasive disease-free survival (HR = 0.83; [95%CI 0.31–2.23], p = 0.71) did not differ between both arms. [ABSTRACT FROM AUTHOR]

The authors aimed to identify risk factors associated with prolonged mechanical ventilation (PMV) after scheduled cardiac surgery under cardiopulmonary bypass (CPB). A single-center, observational study. Tertiary hospital. All adult patients who underwent scheduled cardiac surgery under cardiopulmonary bypass between January 2017 and December 2017. None. Among the 568 patients included, 68 (12.0%) presented a PMV. The median ventilation time was 5.7 hours in the group without PMV and 85.2 hours in the group with PMV. A logistic regression found five variables independently associated with the occurrence of PMV: (1) prior cardiac surgery, (2) preoperative congestive heart failure, (3) preoperative creatinine clearance <30 mL/min/1.73 m², (4) intraoperative implantation of extracorporeal membrane oxygenation, and (5) serum lactate >4 mmol/L on admission. A predictive score to allow the authors to anticipate PMV was developed from the regression coefficient of perioperative factors independently associated with PMV. With a threshold of 2/13, the score had a sensitivity of 80.9%, a specificity of 80.5%, a positive predictive value of 37.2%, and a negative predictive value of 96.7%. The score then was validated in a distinct cohort. The study authors have developed a simple score to predict PMV in patients undergoing cardiac surgery with CPB. This score could allow clinicians to identify a high-risk population that might benefit from specific management upon arrival in the intensive care unit. [ABSTRACT FROM AUTHOR]

Context: The prevalence of bleeding episodes in malignant wounds (MW) is poorly documented, with no distinction between minor and potentially severe bleedings. This affects the quality of care.Objectives: Assessing the frequency and management of hemorrhagic malignant wounds at Institut Curie hospital, an anti cancer center.Methods: Retrospective study conducted from the medical records of patients followed up by the Research and Wound Care Unit from Curie Institute (Paris, France), between 2017 and 2018. Patients >18 years of age, seen at least once by the Unit, and with an MW > 10 cm2 were included.Results: Ninety patients were included, 74.4% female and 25.6% male, with a median age of 64 years (32-92). The most frequent etiologies were breast cancer (52.2%), sarcomas (12.2%), squamous cell carcinoma ear, nose and throat (11%), and pelvic cancer (8.9%). The median survival of patients after their first consultation was 5.6 months (95% CI: 4.6-8.4). Minor bleedings were observed in 38.9% of situations. Bleedings were significantly higher in malignant fungating wounds (P < 0.01). They were treated by the application of alginate or nonadherent dressings. The presence of at least one minor bleeding significantly increased the risk of more severe bleedings (P < 0.001). Hemorrhagic episodes were reported in 18.9% of patients, and 2.2% of patients died as a result of these bleeding episodes. Hemorrhages were fully controlled by hemostatic dressings in 70.6% of cases. The appearance of bleeding (minor or hemorrhagic) was significantly associated with survival (P < 0.001).Conclusion: MWs with bleedings appear to be associated with a poor prognosis and could be a reason for early palliative care even if the patient's general condition is preserved. Palliative care must incorporate wound care skills to provide the most appropriate solutions to this anxiety-provoking symptom. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

After treatment of primary ocular uveal melanoma (UM), up to 50% of patients will develop metastases, mostly in the liver. Systemic treatments do not provide any overall survival benefit for these patients and surgery remains the most effective therapy for selected patients. Radiofrequency ablation (RFA) alone or in combination with surgery is frequently used to spare hepatic parenchyma. When patients relapse after treatment of their first metastases, and when the liver recurrence is limited, new local liver treatment is questionable. A total of 14 patients with liver metastases from uveal melanoma (LMUM) were retrospectively evaluated. All patients had a complete first liver resection and a second treatment with RFA. Overall survival, recurrence-free interval after the first and the second treatment was evaluated. Treatment of hepatic recurrence was percutaneous RFA for ten patients and per-operative RFA for four patients associated with new metastasectomy. The median time to onset of LMUMs after ocular UM treatment was 50 months, and the median time to recurrence of hepatic metastasis after the first liver treatment was 20 months. The overall survival was 70% at five years and 35% at ten years. The recurrence-free interval was 50% and 56% at two years after the first and the second treatment, respectively. Prolonged survival can be achieved by exclusive and iterative local treatment combining surgery and RFA in a small proportion of patients with a first recurrence of isolated LMUM. [ABSTRACT FROM AUTHOR]

The placenta is a unique organ, given that it resides at the interface between two human beings – the mother and the fetus. Additionally, it changes throughout gestation in such a dynamic way that identifying the normal histology can be a challenge in and of itself. This article summarizes the most common pathologic changes in the placenta, devoting the greatest amount of information to the inflammatory disorders and abnormalities of fetal and maternal perfusion. These include acute chorioamnionitis and funisitis/chorionic plate vasculitis, chronic villitis, and changes secondary to maternal vasculopathy and fetal thrombosis. Less common abnormalities that are either often seen or important to identify are described, and the findings in the most common perinatal infections are summarized. Finally, the clinical associations of the placental pathologic findings are described. The intent is to provide a framework for diagnosing common placental abnormalities, and references are provided for further reading. [ABSTRACT FROM AUTHOR]

Although Ti-6Al-4V is the most commonly used titanium alloy in the aerospace industry, the mechanisms governing crack initiation in the different fatigue regimes are not well understood yet. This situation partly pertains to a competition between multiple crack initiation mechanisms. In particular, applied loading conditions were identified as a key parameter governing the transition between mechanisms. The fatigue behavior of Ti-6Al-4V with a bi-modal microstructure was investigated in the present study using different waveforms, load ratios and frequencies to clarify this feature. A detailed characterization of the main crack initiation sites was carried out to identify microstructural configurations governing crack nucleation in low-cycle dwell-fatigue, low-cycle fatigue and high-cycle fatigue regimes. While lifetimes and fracture surfaces showed a good consistency with data from prior studies, a single microstructural configuration was found involved with the formation of crack initiation facets. All investigated cracks leading to specimen failure were nucleated along (0001) twist grain boundaries exhibiting similar features. Based on this finding, a criterion is proposed to identify candidates for crack initiation. This also demonstrates no major sensitivity of the critical microstructural configurations to environment, free surface, loading conditions and, as shown in previous studies, microstructure and composition. However, conventional fatigue failure results from one, or a few, surface or subsurface crack initiation sites while dwell-fatigue failure involves the formation of multiple internal cracks. This is accompanied by a significant dwell-fatigue life debit at peak stress magnitudes close to the yield strength. Features of microstructural configurations prone to crack nucleation are finally compared with data reported in existing literature to propose a mechanism of crack formation in Ti alloys. [Display omitted] [ABSTRACT FROM AUTHOR]

Cardiac aging is characterized by cardiomyocyte loss, hypertrophy of the remaining cardiomyocytes and replacement fibrosis, leading to diastolic dysfunction. However, mechanisms involved in age-associated cellular loss such as apoptosis, necroptosis, and/or autophagy, remain controversial but are crucial in age-associated pathologies such as non-insulin dependent diabetes mellitus (NIDD) and atrial fibrillation (AF). The objectives of the present study are to identify the mechanisms involved in cardiomyocytes loss and atrial remodeling during aging. Atrial samples (residues of transection of the right atrial appendage for extracorporeal circulation placement) were collected from patients undergoing coronary artery bypass graft from 36 to 83 years old (yo), with or without history of myocardial infarction (MI), (INSERM IRB authorization n C-19-71). Only patients without NIDD and/or AF were studied (n = 41). After trabeculae dissection and protein extraction, Beclin-1, RIPK3, pro- and cleaved caspase 3 as well as JNK, ERK, AMPK, P38 MAPK and STAT3 pathways were quantified by western blotting in cytosolic fractions and expressed as normalized densitometric score. Phospho-ERK/ERK and phospho-p38 MAPK levels increased with age (factorial ANOVA; respectively P < 0.001 and P < 0.05) but not with MI. In addition, RIPK3 content increased in samples from patients without MI over 70 yo as compared to patients under 55 yo (1.88 ± 0.23 vs. 0.69 ± 0.27; P < 0.05) and was associated with an activation of JNK pathway (phospho-JNK/JNK level: 2.28 ± 0.98 vs. 0.37 ± 0.09; P < 0.05). In contrast, no significant change was observed for Beclin-1 or caspase 3 levels. In patients with MI over 70 yo, as compared to patients of the same age without MI, Beclin-1 (1.26 ± 0.17 vs. 0.83 ± 0.14, P < 0.05) and phospho-STAT3/STAT3 levels (3.09 ± 0.98 vs. 1.18 ± 0.75; P < 0.05) were increased but surprisingly RIPK3 levels were reduced (1.18 ± 0.19 vs. 1.88 ± 0.23; P < 0.05). The age-associated activation of JNK in atria may lead to the loss of Cx43 protein resulting in impaired conduction and contributing to the increasing risk of AF. In addition, the ERK activation, promoting cell survival, is counterbalanced by activation of p38 MAPK, mediating pro-inflammatory cytokine production, and increased RIPK3 suggesting increased necroptosis, without apoptosis. In patients with MI, the high level of Beclin-1 suggests an upregulation of autophagy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Since indication extension to children data regarding the effectiveness of levetiracetam in paediatric patients remains limited. Aims: Investigate the real-life effectiveness of levetiracetam in paediatric patients. Methods: Epileptic children (<16 years) who had initiated levetiracetam between the 1 October 2006 and the 31 March 2007 were included and followed for 1 year by hospital or non-hospital neurologists practising in France. Results: Among the 156 identified children, 147 were analysed: 51.7% were female, and mean (SD) age was 9.2 years (4.2). Most patients had either partial symptomatic (30.6%) or partial cryptogenic (26.5%) epilepsy, 92.5% experienced seizures during the 6 months preceding levetiracetam initiation, and 19.2% were on levetiracetam alone at initiation. One-year levetiracetam continuation rate was estimated to be 72.0% (95%CI [63.8; 78.6]). Of the 104 children continuing levetiracetam treatment at end of study, 31.7% were seizure-free during the last six months of follow-up, and 23.1% on levetiracetam alone. Discontinuation of levetiracetam (n = 41) was mainly for insufficient efficacy (58.5% of those concerned). Conclusions: In real-life clinical practice important treatment retention and non-negligible reduction of seizure frequency may be expected. [Copyright &y& Elsevier]

Abstract: The chemical synthesis of UDP-6-NHAc-6-deoxy-Galf was performed and it led to the isolation of both pure anomers. They were then evaluated together with the previously prepared UDP-furanoses for their anti-parasitic properties against Leishmania donovani promastigotes, one of the agents responsible for visceral leishmaniasis. Amongst them, the unnatural 1,2-trans UDP-6-NHAc-Galf demonstrated a high potency in inhibiting the growth of the parasite. [Copyright &y& Elsevier]

Abstract: Tearing in infancy is a very frequent symptom, particularly during the first year of life. A definite diagnosis can be made easily, only by questioning the parents about the characteristics and the evolution of the tearing since the birth and with a simple examination. The main causes are congenital nasolacrimal duct obstruction account of his high frequency in infant and congenital glaucoma account of his seriousness. [Copyright &y& Elsevier]

• Micro-aethalometers were used to monitor personal exposure to Black Carbon (BC). • Trips by public transport and private motorized transport were associated with a higher personal exposure to BC. • Trips with cycling were associated with the highest inhaled doses of BC. • Inhalation should be taken into account for a proper assessment of the exposure burden during trips. Epidemiological evidence suggests that motorized vehicle users have a higher air pollutant exposure (especially from vehicle exhaust) than active (walking or cycling) transport users. However, studies often relied on insufficiently diverse sample and ignored that minute ventilation has an effect on individuals' inhaled dose. This study examined commuters' breathing zone concentration and inhaled doses of black carbon (BC) when travelling by different transport modes in the Grand Paris region. Personal exposure to BC was continuously measured with MicroAethalometer (MicroAeth AE51) portable monitors strapped on participants' shoulder with tube inlet at the level of the neck (breathing zone), and inhaled doses were derived from several methods estimating ventilation [based on metabolic equivalents from accelerometry [METs], heart rate, and breathing rate]. Trip stages and transport modes were assessed from GPS and mobility survey data. Breathing zone concentrations and inhaled doses of BC were compared across transport modes at the trip stage level (n = 7495 for 283 participants) using linear mixed effect models with a random intercept at individual level. Trip stages involving public transport and private motorized transport were associated with a 2.20 µg/m3 (95% CI: 1.99, 2.41) and 2.29 µg/m3 (95% CI: 2.10, 2.48) higher breathing zone concentration to BC than walking, respectively. Trip stages with other active modes had a 0.41 µg (95% CI: 0.25, 0.57) higher inhaled dose, while those involving public transport and private motorized transport had a 0.25 µg (95% CI: −0.35, −0.15) and 0.19 µg (95 %CI: −0.28, −0.10) lower inhaled dose of BC per 30 min than walking. The ranking of transport modes in terms of personal exposure was markedly different when breathing zone concentrations and inhaled doses were considered. Future studies should take both into account to explore the relationship of air pollutants in transport microenvironments with physiological response. [ABSTRACT FROM AUTHOR]

Les deux premières années de la vie sont essentielles pour le développement de la fonction visuelle. Les difficultés de l’examen du nourrisson nécessitent de le faire précéder d’un interrogatoire rigoureux : antécédents personnels et familiaux, signe ayant motivé la consultation, évolution. L’inspection apporte également nombre de renseignements : malformations, comportement visuel, anomalie oculomotrice. L’évaluation de la fonction visuelle à cet âge exige des techniques particulières, ainsi que l’étude de la réfraction objective. Enfin, l’examen du segment antérieur et postérieur, s’il fait appel à un matériel usuel, nécessite une technique particulière et révèle des pathologies spécifiques au nourrisson. Tout au long de l’examen, la patience et la douceur permettent d’aboutir plus simplement à un diagnostic fiable. [Copyright 2004 Elsevier]

Copyright of EMC-Pediatrie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Persistent tearing in infancy is frequent. The evolution of the symptom and a simple examination generally leads to a definite diagnosis and therapeutic orientation. The main cause is congenital nasolacrimal duct obstruction. Nevertheless, some symptoms correspond to other causes such as congenital glaucoma with clear tearing, megalocornea and corneal oedema, or particular forms of chronic conjunctivitis or keratitis. [Copyright &y& Elsevier]

Many ocular traumas in childhood occur at home, and are at risk for unilateral visual loss. Gentle examination allows to check for signs requiring an ophthalmic examination and initiate the first-step treatment. Many lesions are superficial and completely resolve after topical treatment. Penetrating injuries and contusions can lead to profound amblyopia. Concerning the orbitopalpebral traumas, paediatric specificities need to be taken in account. Amblyopia and its treatment is a central point for the prognosis and encourages prevention. [Copyright &y& Elsevier]

Background The French HTA agency requested a real-life benefit-risk study of ticagrelor (T) compared to clopidogrel (C) and prasugrel (P) in the secondary prevention of acute coronary syndrome (ACS) (EUPAS5987). Purpose This study aimed to identify the risk factors associated with the primary effectiveness endpoint for patients with antiplatelet agents after a hospitalisation for ACS. Methods Patients hospitalised in 2013 for STEMI, NSTEMI or unstable angina, with intensive care unit (ICU) stay, and followed for 1 year in the nationwide French claims and hospitalisation database, SNIIRAM. Treatment group (T, C, or P ± aspirin) was defined by the first drug dispensed in the month after discharge. The primary effectiveness endpoint was a composite of the first event of ACS with ICU stay, stroke, or all-cause death. Hazard ratios were estimated with Cox proportional hazard risk model (multivariate analysis). Results A total of 41,954 patients were included (19,796 C, 13,916 T, 8242 P) with different characteristics: mean age of 72, 63, 58 years, respectively; 68%, 76%, 86% male; 42%, 55%, 72% STEMI. A Charlson comorbidity index > 5 was associated with a risk increased by at least 50% for the primary effectiveness endpoint; age, a poverty index, ICU stay duration > 5 days and no PCI during index hospitalisation, and congestive heart failure, peripheral arterial disease, ischemic stroke, abnormal renal function, C and P before index hospitalisation were associated with a risk increased by 20–50%; diabetes, hypertension, aspirin before index hospitalisation, and C in the month after discharge (versus T) were associated with a risk increased by 10–20%. Conclusions In this nationwide real-life study, the risk factor most associated with the primary effectiveness endpoint was a Charlson comorbidity index > 5. [ABSTRACT FROM AUTHOR]

Background Diabetic patients have an increased QT interval duration corrected for heart rate (QTcF) and an increased risk of sudden death, as compared to healthy subjects. Diabetics are characterized by increased insulin resistance and are frequently affected by autonomic neuropathy and other hormonal disorders, such as hypogonadism and decreased IGF1 levels. Data regarding influence of these latter conditions on QT interval duration in diabetics are scarce. Methods A cohort of 195 type II diabetic patients at high cardiovascular risk were prospectively included. Circulating concentrations of FSH, testosterone, insulin, glycaemia, kalemia, HbA1c were measured concomitantly to the recording of a digitized electrocardiogram. Orthostatic hypotension was evaluated at the same time, as a surrogate of autonomic neuropathy. Treatments influencing QTc were recorded and classified according to Crediblemeds ® . Results The cohort consisted of 154 men (79%) aged 64.8 ± 8.6 years with a mean QTcF of 418 ± 25 msec. Eleven patients (5.6%) were taking a medication belonging to Crediblemeds’ known Torsade de Pointe risk category. Twenty-six patients (13.3%) had an orthostatic hypotension. According to multivariable analysis, age (β = 0.14, P = 0.04), presence of orthostatic hypotension (β = 0.14, P = 0.02), intake of medication at known risk of Torsade de Pointe (β = 0.22, P = 0.001), HbA1c, kalemia and FSH levels (β = 0.232, P < 0.001; β = −0.187, P = 0.005; β=0.14, P = 0.04; respectively) were related to QTcF ( r 2 = 0.22, P < 0.01). Conclusion In diabetic patients, cardiac repolarization is influenced by complex interactions between presence of autonomic neuropathy, gonadotropins, poor glycemic control and ionic disturbances. [ABSTRACT FROM AUTHOR]

Purpose: Disseminated tumor cells (DTCs) collect in the bone marrow and indicate micrometastatic spread. We previously reported that DTCs could be a predictive factor for the efficacy of regional node irradiation (internal mammary nodes [IMNs]/supra- and infraclavicular nodes [SCNs]). In this article, we report the long-term results (>10 years) on the impact of DTC status in early stage breast cancer.Methods and Materials: Patients with localized breast cancer were eligible for inclusion in this prospective cohort. DTCs were obtained from a medullary iliac crest sample performed before any primary therapy. DTC status was prospectively assessed by pathologists. Irradiation volumes were defined per standard of care. Cumulative incidence rates and hazard ratios were obtained using both Cox and Fine-Gray models. Interaction tests were performed to confirm the predictive value of DTC status in a multivariate analysis.Results: Six hundred twenty patients with localized breast cancer were included. Overall, 94 patients (15.2%) were DTC-positive. After a median follow-up of 11.7 years, 47 patients (7.6%) experienced locoregional relapse. DTC detection was associated with a higher risk of locoregional relapse in univariate and multivariate analyses (Cox hazard ratio, 3.26; 95% confidence interval, 1.6-5.7; P = .001). In the multivariate subgroup analysis, IMN/SCN irradiation significantly reduced locoregional relapse among DTC-positive patients compared with DTC-negative patients (interaction test: hazard ratio, 0.3; 95% confidence interval, 0.1-0.9; P = .02). IMN/SCN was the only irradiation volume with an impact on locoregional relapse in patients according to DTC status, and the predictive value of DTC status for the benefit of locoregional irradiation was independent of locoregional nodal status.Conclusions: This long-term analysis confirms the predictive impact of DTC status on the efficacy of regional radiation therapy for locoregional relapse in early breast cancer. After further studies, DTC status could be used as a decision tool to better tailor adjuvant radiation therapy in patients with early stage breast cancer. [ABSTRACT FROM AUTHOR]

Background Palbociclib is a CDK4/6 inhibitor with demonstrated efficacy and safety in combination with endocrine therapy in advanced luminal breast cancer (LBC). We evaluated the respective efficacy and safety of chemotherapy and letrozole–palbociclib (LETPAL) combination as neoadjuvant treatment in patients with high-risk LBC. Patients and methods NeoPAL (UCBG10/4, NCT02400567) is a randomised, parallel, non-comparative phase II study. Patients with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II–III breast cancer, not candidate for breast-conserving surgery, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks, or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2)×3 21-day courses followed by docetaxel 100 mg/m2×3 21-day courses. Primary end point was residual cancer burden (RCB 0–I rate). Secondary end points included clinical response, proliferation-based markers, and safety. Results Overall, 106 patients were randomised [median Prosigna® ROR Score 71 (22–93)]. RCB 0–I was observed in four and eight patients in LETPAL [7.7% (95% CI 0.4–14.9)] and chemotherapy [15.7% (95% CI 5.7–25.7)] arms, respectively. Pathological complete response rates were 3.8% and 5.9%. Clinical response (75%) and breast-conserving surgery rates (69%) were similar in both arms. Preoperative Endocrine Prognostic Index 0 scores (breast cancer-specific survival) were observed in 17.6% and 8.0% of patients in LETPAL and chemotherapy arms, respectively. Safety profile was as expected, with 2 versus 17 serious adverse events (including 11 grade 4 serious AEs in the chemotherapy arm). Conclusion LETPAL combination was associated with poor pathological response but encouraging clinical and biomarker responses in Prosigna®-defined high-risk LBC. Contemporary chemotherapy regimen was associated with poor pathological and biomarker responses, with a much less favourable safety profile. LETPAL combination might represent an alternative to chemotherapy in early high-risk LBC. Clinical Trial Number NCT02400567. [ABSTRACT FROM AUTHOR]

Introduction La perfusion d’émulsion lipidique est recommandée comme antidote dans les intoxications aux anesthésiques locaux (AL) bien que son effet n’ait pas été démontré de manière contrôlée. Parmi les mécanismes d’action évoqués, le principal, Lipid Sink Theory, impliquerait la captation au sein des chylomicrons lipidiques des molécules d’AL et donc la création d’un volume de distribution additionnel. Ce modèle a été validé chez l’animal mais non chez l’homme. Nous avons conduit une étude pharmacocinétique de population pour tester cette hypothèse chez des volontaires. Matériel et méthodes Dans cette étude randomisée, double insu, en crossover , 16 volontaires (8 hommes, 8 femmes) ont reçu une perfusion continue de ropivacaine (ROP) ou de lévobupivacaine (LEVO) (8 mg/min, maximum 120 mg) et 2 min après le début de la perfusion un bolus de 120 d’Intralipide ® 20 % (IL) ou de sérum physiologique (CPP IdF 6, NCT01602250 ). La perfusion d’AL était arrêtée à la manifestation des premiers signes d’imprégnation neurologique de toxicité par les volontaires ( T 0). Des prélèvements sanguins ont été effectués à T 0, puis 2, 5, 8, 12, 20, 30 et 45 min puis 1, 2, 3, 6 et 8 h pour mesure de la concentration d’AL par chromatographie en phase gazeuse. Un modèle à deux compartiments a permis de calculer pour chacun des AL, volume initial de distribution ( V c) et clairance totale (Cl). Un compartiment additionnel ( V dIL), décroissant exponentiellement avec le temps, a été ajouté à V c, correspondant à l’IL selon la théorie du Lipid Sink. Nous avons utilisé le logiciel NONMEM V6. Le pic de concentrations observé ( C max ) est rapporté. Résultats Les doses moyennes administrées n’étaient pas différentes en présence d’Intralipide ® ou de placebo pour la ROP (75,7 ± 29,1 mg vs 81,7 ± 22,3 mg, respectivement) et pour la LEVO (69,4 ± 26,2 mg vs 80,8 ± 31,7 mg, respectivement). Les C max n’étaient pas différentes entre les 4 groupes ( Tableau 1 ), toutefois, il existait une différence de C max des AL selon la présence d’IL ou PHY ( p = 0,015). Les co-variables poids et sexe ajoutées à V c et clairance ne modifiaient pas la pharmacocinétique du modèle. Lorsqu’il était perfusé, l’IL induisait un volume de distribution additionnel augmentant le volume de distribution initial de près de 20 %. La demi-vie de disparition de ce volume additionnel était de 45 min. Discussion Cette étude est la première à mettre en évidence la réalité du mécanisme d’action par Lipid Sink chez l’homme. L’IL induit un volume de distribution de 8,43 L et de 13,3 L pour la ROP et la LEVO, respectivement, ce qui diminue la concentration au pic de 25 % pour la ROP et de 30 % pour la LEVO. Cette diminution ne paraît toutefois pas suffisante pour prévenir la toxicité aux AL pour des concentrations usuelles mais pourrait se révéler pertinente pour de fortes concentrations. Ce volume de distribution disparaît avec une demi-vie de 45 min. [ABSTRACT FROM AUTHOR]

To describe clinical features, management, and outcomes of posterior persistent fetal vasculature (PFV) and suggest a management algorithm. Retrospective, consecutive case series. All children diagnosed with posterior PFV and treated or followed at the Rothschild Foundation Hospital in France between June 2011 and September 2021. Retrospective analysis of the clinical characteristics of posterior PFV. We reported age, gender, presenting symptoms, intraocular pressure, and visual acuity (VA) at diagnosis. Patients were divided into 4 groups depending on the severity and involvement or not of anterior segment. We reported the vitreoretinal surgical techniques used. Anatomic results, ocular hypertension, best-corrected distance visual acuity (BCDVA), presence of postoperative adverse events, and additional surgical interventions were recorded at each follow-up visit. Ninety-six patients were included. The median age at diagnosis was 8 months (IQR = 12), mean 18.9 ± 30.9 months) with a mean follow-up of 27 ± 31.2 months. Although PFV is often an isolated disease, it was associated with a systemic disease in 8% of cases. There was anterior involvement in 62 (64%) of eyes. Forty-one eyes (42.7%) were microphthalmic and more frequently associated with severe PFV (53% vs. 25%; P = 0.01). Surgery was performed in 85 patients (89%). Of them, 69 (81%) had a total success, 5 (6%) had a partial success due to persistent limited peripheral retinal detachment (RD), and 11 (13%) had a failure due to persistent total RD after surgery. Postoperative adverse events occured in 38 eyes including ocular hypertension requiring eye drop medication (7.1%), secondary cell proliferation around the intraocular lens (8.2%), intravitreal hemorrhages (7.1%), and persistent tractional RD (10.6%). Second surgery was performed in 18 patients (21%). At last follow-up, VA could be measured in logarithm of the minimum angle of resolution in 43 children (45%), light perception in 21 eyes (22%), and no light perception or impossible to assess in 32 eyes (33%). In our case series, most patients presenting with posterior PFV received complex vitreoretinal surgery. Goals of the surgery vary and include retinal flattening, reduction of vitreoretinal traction, freeing of visual axis, and aesthetic concerns. We propose a surgical and medical management algorithm for PFV. Proprietary or commercial disclosure may be found after the references. [ABSTRACT FROM AUTHOR]

Data on the role of the microbiota in cancer have accumulated in recent years, with particular interest in intratumoral bacteria. Previous results have shown that the composition of intratumoral microbiome is different depending on the type of primary tumour and that bacteria from the primary tumour could migrate to metastatic sites. Seventy-nine patients with breast, lung, or colorectal cancer and available biopsy samples from lymph node, lung, or liver site, treated in the SHIVA01 trial were analysed. We performed bacterial 16S rRNA gene sequencing on these samples to characterise the intratumoral microbiome. We assessed the association between microbiome composition, clinicopathological characteristics, and outcomes. Microbial richness (Chao1 index), evenness (Shannon index) and beta-diversity (Bray Curtis distance) were associated with biopsy site (p = 0.0001, p = 0.03 and p < 0.0001, respectively) but not with primary tumour type (p = 0.52, p = 0.54 and p = 0.82, respectively). Furthermore, microbial richness was inversely associated with tumour-infiltrating lymphocytes (TILs, p = 0.02), and PD-L1 expression on immune cells (p = 0.03), or assessed by Tumor Proportion Score (TPS, p = 0.02) or Combined Positive Score (CPS, p = 0.04). Beta-diversity was also associated with these parameters (p < 0.05). Patients with lower intratumoral microbiome richness had shorter overall survival (p = 0.03) and progression-free survival (p = 0.02) in multivariate analysis. Biopsy site, rather than primary tumour type, was strongly associated with microbiome diversity. Immune histopathological parameters such as PD-L1 expression and TILs were significantly associated with alpha and beta-diversity supporting the cancer-microbiome-immune axis hypothesis. • The composition of microbiota in metastases is tissue-rather than tumor-driven. • PD-L1 and tumor-infiltrating lymphocytes are associated with microbiome diversity. • This ancillary study supports the cancer-microbiome-immune axis hypothesis. [ABSTRACT FROM AUTHOR]

Abstract: The new international regulations that limit the ambient PM2.5 levels necessitated reliable methods to monitor and report these very fine particulate matter emissions from contributing sources. Due to the inadequacies of conventional stack sampling methods, source dilution techniques were developed in particulate matter (PM) measurement from combustion sources to closely simulate realistic atmospheric conditions where hot stack gases transform to very fine secondary aerosols. Using such dilution samplers, a PM2.5 database from coal-fired utility boilers was initiated using field measurement results. Fuels include blends of Canadian subbituminous, Canadian lignite and US Powder River Basin coals. PM2.5 concentration results, along with their elemental and sulphate constituents found in emissions from utility boilers, are discussed in conjunction with coal feed properties. The nature of ultra-fine components found in stack emission is briefly reported. [Copyright &y& Elsevier]

Abstract: There is no doubt now that the synthesis of compounds of varying complexity such as saccharides and derivatives thereof continuously grows with enzymatic methods. This review focuses on recent basic knowledge on enzymes specifically involved in the biosynthesis and degradation of furanosyl-containing polysaccharides and conjugates. Moreover, and when possible, biocatalyzed approaches, alternative to standard synthesis, will be detailed in order to strengthen the high potential of these biocatalysts to go further with the preparation of rare furanosides. Interesting results will be also proposed with chemo-enzymatic processes based on nonfuranosyl-specific enzymes. [Copyright &y& Elsevier]