Search

Introduction: Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs., Methods: We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, n = 14) or chronic infection (SR/CI, n = 8)., Results: Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4 + CXCR5 + PD-1 + ICOS + FoxP3 - ) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19 + CD27 + IgM - E2-Tet + ) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3 + CCR6 - ) subset correlated with the neutralization breadth and potency of NAbs., Conclusion: These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eisa, Gomez-Escobar, Bédard, Abdeltawab, Flores, Mazouz, Fieffé-Bédard, Sakayan, Gridley, Abdel-Hakeem, Bruneau, Grakoui and Shoukry.)

Deep dermatophytosis is a dermal infection caused by Dermatophytes. It can cause deeper dermal dermatophytosis, Majocchi's granuloma, dermatophytic pseudomycetoma or a widespread infection. CARD9 deficiency is a known risk factor in the Mediterranean region, first reported in 1964 in Morocco. We report a case of 23-year-old man with a scarring alopecia who presented with subcutaneous abscesses topped off with a large ringworm infection. Mycotic analysis revealed a Trichophyton Rubrum deep dermatophytosis. The molecular study revealed a CARD9 mutation confirming dermatophytosis with parotid and lymph nodes involvement. The patient underwent successful drainage surgery of the abscesses alongside medical treatment including antifungal agents and he was discharged after an uneventful postoperative course., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2023.)

Successive episodes of hepatitis C virus (HCV) infection represent a unique natural rechallenge experiment to define correlates of long-term protective immunity and inform vaccine development. We applied a systems immunology approach to characterize longitudinal changes in the peripheral blood transcriptomic signatures in eight subjects who spontaneously resolved two successive HCV infections. Furthermore, we compared these signatures with those induced by an HCV T cell-based vaccine regimen. We identified a plasma cell transcriptomic signature during early acute HCV reinfection. This signature was absent in primary infection and following HCV vaccine boost. Spontaneous resolution of HCV reinfection was associated with rapid expansion of glycoprotein E2-specifc memory B cells in three subjects and transient increase in E2-specific neutralizing antibodies in six subjects. Concurrently, there was an increase in the breadth and magnitude of HCV-specific T cells in 7 out of 8 subjects. These results suggest a cooperative role for both antibodies and T cells in clearance of HCV reinfection and support the development of next generation HCV vaccines targeting these two arms of the immune system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Mazouz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl 4 -induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F + Kupffer cells (KCs) and infiltrating IBA1 + CLEC4F - monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Flores Molina, Abdelnabi, Mazouz, Villafranca-Baughman, Trinh, Muhammad, Bédard, Osorio Laverde, Hassan, Di Polo and Shoukry.)

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a major health problem with complex pathogenesis. Although sex differences in NAFLD pathogenesis have been reported, the mechanisms underlying such differences remain understudied. Interleukin (IL)22 is a pleiotropic cytokine with both protective and/or pathogenic effects during liver injury. IL22 was shown to be hepatoprotective in NAFLD-related liver injury. However, these studies relied primarily on exogenous administration of IL22 and did not examine the sex-dependent effect of IL22. Here, we sought to characterize the role of endogenous IL22-receptor signaling during NAFLD-induced liver injury in males and females., Methods: We used immunofluorescence, flow cytometry, histopathologic assessment, and gene expression analysis to examine IL22 production and characterize the intrahepatic immune landscape in human subjects with NAFLD (n = 20; 11 men and 9 women) and in an in vivo Western high-fat diet-induced NAFLD model in IL22RA knock out mice and their wild-type littermates., Results: Examination of publicly available data sets from 2 cohorts with NAFLD showed increased hepatic IL22 gene expression in females compared with males. Furthermore, our immunofluorescence analysis of liver sections from NAFLD subjects (n = 20) showed increased infiltration of IL22-producing cells in females. Similarly, IL22-producing cells were increased in wild-type female mice with NAFLD and the hepatic IL22/IL22 binding protein messenger RNA ratio correlated with expression of anti-apoptosis genes. The lack of endogenous IL22-receptor signaling (IL22RA knockout) led to exacerbated liver damage, inflammation, apoptosis, and liver fibrosis in female, but not male, mice with NAFLD., Conclusions: Our data suggest a sex-dependent hepatoprotective antiapoptotic effect of IL22-receptor signaling during NAFLD-related liver injury in females., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years, walkability is increasingly integrated into sustainability strategies, considering its many health and environmental benefits. Besides, thermal comfort also has been progressively promoted as a critical measure for pedestrian comfort and wellbeing. Despite the relevance of the two concepts, few studies combined them in a comprehensive model. This study considers thermal comfort in assessing walkability by developing a new measurement tool, the Street Walkability and Thermal Comfort Index (SWTCI), which focuses on comfort facilities and Physiological Equivalent Temperature (PET), at the street scale. The applied point system method requires combining a questionnaire survey, observations, and in situ measurements (air temperature, wind velocity, and relative humidity). The questionnaire survey (330 responders) measured 21 street design indicators' importance, using a five-point Likert scale ranging from 1 (least important) to 5 (very important). The observation technique seeks to evaluate every pedestrian comfort indicator score (Si s ). The in situ measurements permit Envi-met's calibrated data validation and getting the mean radian temperature (T mrt ). Those were considered in the PET's calculation using Rayman software. Three distinct streets have been chosen in Annaba city, Algeria, within the Mediterranean climate (Csa). The results show that the SWTCI achieves its highest score on the three streets when the thermal perception is neutral (20 < PET <26), and its lowest score, with a warm thermal sensation (28 < PET < 31). Despite the divergence in PET values, the highest score of SWTCI was 33%, reflecting a low comfort quality and minimal pedestrian facilities. Applying the SWTCI method can transform uncomfortable streets into an ideal walkable and pleasant path by finding the problems and proposing improvements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hepatitis C virus (HCV) infection resolves spontaneously in ∼25% of acutely infected humans where viral clearance is mediated primarily by virus-specific CD8 + T cells. Previous cross-sectional analysis of the CD8 + TCR repertoire targeting two immunodominant HCV epitopes reported widespread use of public TCRs shared by different subjects, irrespective of infection outcome. However, little is known about the evolution of the public TCR repertoire during acute HCV and whether cross-reactivity to other Ags can influence infectious outcome. In this article, we analyzed the CD8 + TCR repertoire specific to the immunodominant and cross-reactive HLA-A2-restricted nonstructural 3-1073 epitope during acute HCV in humans progressing to either spontaneous resolution or chronic infection and at ∼1 y after viral clearance. TCR repertoire diversity was comparable among all groups with preferential usage of the TCR-β V04 and V06 gene families. We identified a set of 13 public clonotypes in HCV-infected humans independent of infection outcome. Six public clonotypes used the V04 gene family. Several public clonotypes were long-lived in resolvers and expanded on reinfection. By mining publicly available data, we identified several low-frequency CDR3 sequences in the HCV-specific repertoire matching human TCRs specific for other HLA-A2-restricted epitopes from melanoma, CMV, influenza A, EBV, and yellow fever viruses, but they were of low frequency and limited cross-reactivity. In conclusion, we identified 13 new public human CD8 + TCR clonotypes unique to HCV that expanded during acute infection and reinfection. The low frequency of cross-reactive TCRs suggests that they are not major determinants of infectious outcome., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Competing Interests: The authors have no conflict of interest to disclose.

The novel coronavirus, named SARS-CoV-2, responsible of the COVID-19 is now causing a pandemic. Detecting all possible cases and eliminating differential diagnoses in front of any acute respiratory distress has become a daily challenge for doctors around the world. We believe that non-COVID patients are the hidden victims of the actual health problematic. We report from this manuscript the case of a patient with fat embolism syndrome that has been suspected as COVID-19., Competing Interests: The authors declare no competing interests., (© Salim Mazouz et al.)

The discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase family that signals in response to collagen and that has been implicated in cancer progression. In the present study, we investigated the expression and role of DDR1 in human melanoma progression. Immunohistochemical staining of human melanoma specimens (n = 52) shows high DDR1 expression in melanoma lesions that correlates with poor prognosis. DDR1 expression was associated with the clinical characteristics of Clark level and ulceration and with BRAF mutations. Downregulation of DDR1 by small interfering RNA (siRNA) in vitro inhibited melanoma cells malignant properties, migration, invasion, and survival in several human melanoma cell lines. A DDR tyrosine kinase inhibitor (DDR1-IN-1) significantly inhibited melanoma cell proliferation in vitro, and ex vivo and in tumor xenografts, underlining the promising potential of DDR1 inhibition in melanoma., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq and blood transcriptome module (BTM) analysis to characterize immune function in peripheral blood mononuclear cells (PBMC) before, during, and after acute HCV infection resulting in spontaneous resolution. Our results provide a detailed description of innate immune programs active in peripheral blood during acute HCV infection, which include prominent type I interferon and inflammatory signatures. Innate immune gene expression rapidly returns to pre-infection levels upon viral clearance. Comparative analyses using peripheral blood gene expression profiles from other viral and vaccine studies demonstrate similarities in the immune responses to acute HCV and flaviviruses. Of note, both acute dengue virus (DENV) infection and acute HCV infection elicit similar innate antiviral signatures. However, while transient in DENV infection, this signature was sustained for many weeks in the response to HCV. These results represent the first longitudinal transcriptomic characterization of human immune function in PBMC during acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure., Competing Interests: The authors have declared that no competing interests exist.

The introduction of small molecules targeting viral functions has caused a paradigm shift in hepatitis C virus (HCV) treatment. Administration of these direct-acting antivirals (DAAs) achieves a complete cure in almost all treated patients with short-duration therapy and minimal side effects. Although this is a major improvement over the previous pegylated interferon plus ribavirin (PEG-IFNα/RBV) standard-of-care treatment for HCV, remaining questions address several aspects of the long-term benefits of DAA therapy. Interferon (IFN)-based treatment with successful outcome was associated with substantial reduction in liver disease-related mortality. However, emerging data suggest a complex picture and several confounding factors that influence the effect of both IFN-based and DAA therapies on immune restoration and limiting liver disease progression. We review current knowledge of restoration of innate and HCV-specific immune responses in DAA-mediated viral elimination in chronic HCV infection, and we identify future research directions to achieve long-term benefits in all cured patients and reduce HCV-related liver disease morbidity and mortality., Competing Interests: The authors have nothing to disclose., (Copyright © 2018 Canadian Association for the Study of the Liver.)

Background: Surgical approaches in neck dissection: comparing functional, oncologic and aesthetic aspects of transverse cervicotomy to Paul André's approach., Methods: This single-center retrospective study compares a new transverse incision for cervicotomy to the classical approach described by Paul André in neck dissections. The evaluation criteria were: number of lymph nodes analyzed, operative time, complications, patient satisfaction and aesthetic aspects of the scar., Results: A total of 34 patients were included in this study, from September 2009 until January 2015. The number of lymph nodes analyzed is not affected by this new approach compared to the classical one (P=0.9). The scar has a significantly more discreet appearance in the transverse cervicotomy group (P=0.023) likewise; patient satisfaction is higher in this group (P=0.006)., Conclusions: Aesthetic and functional impairment can be reduced using this new transverse cervical approach hidden in the natural creases of the neck described by Langer., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: The three-stage folded forehead flap (FFF) proved to be a simple and readily available method of lining replacement. To date, no clinical trial has evaluated the outcomes of the FFF on the nose shape and function., Methods: Patients undergoing a full-thickness unilateral alar reconstruction with a forehead flap between January of 2010 and December of 2015 were included for analysis. Patients were divided into two groups: The FFF group included patients that had a unilateral alar reconstruction using a three-stage FFF; the standard forehead flap (SFF) group included patients that had a reconstruction using a two-stage forehead flap in combination with another method for lining reconstruction. The following objective measurements were performed: the alar thickness, nostril and hemi-nose areas, and nostril height. Subjective evaluation of the results was performed using the NAFEQ score. Independent raters also evaluated the appearance of the nose., Results: Thirty-one patients were included: 15 in the FFF group and 16 in the SFF group. In both groups, the reconstructed ala was thicker than that on the normal side, the reconstructed nostril was smaller than the normal nostril, and the reconstructed hemi-nose was bigger than the normal side. Moreover, 84% of the patients were satisfied with their total nasal functioning. All the patients were satisfied with their total nasal appearance., Conclusion: The FFF showed objective, subjective, aesthetic, and functional results comparable to other lining reconstruction techniques., (Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Chronic viral infections remain a global health concern. The early events that facilitate viral persistence have been linked to the activity of the immunoregulatory cytokine IL-10. However, the mechanisms by which IL-10 facilitates the establishment of chronic infection are not fully understood. Herein, we demonstrated that the antigen sensitivity of CD8 + T cells was decreased during chronic infection and that this was directly mediated by IL-10. Mechanistically, we showed that IL-10 induced the expression of Mgat5, a glycosyltransferase that enhances N-glycan branching on surface glycoproteins. Increased N-glycan branching on CD8 + T cells promoted the formation of a galectin 3-mediated membrane lattice, which restricted the interaction of key glycoproteins, ultimately increasing the antigenic threshold required for T cell activation. Our study identified a regulatory loop in which IL-10 directly restricts CD8 + T cell activation and function through modification of cell surface glycosylation allowing the establishment of chronic infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

PKR is a cellular kinase involved in the regulation of the integrative stress response (ISR) and pro-inflammatory pathways. Two N-terminal dsRNA Binding Domains (DRBD) are required for activation of PKR, by interaction with either dsRNA or PACT, another cellular DRBD-containing protein. A role for PKR and PACT in inflammatory processes linked to neurodegenerative diseases has been proposed and raised interest for pharmacological PKR inhibitors. However, the role of PKR in inflammation is subject to controversy. We identified the flavonoid luteolin as an inhibitor of the PKR/PACT interaction at the level of their DRBDs using high-throughput screening of chemical libraries by homogeneous time-resolved fluorescence. This was further validated using NanoLuc-Based Protein Complementation Assay. Luteolin inhibits PKR phosphorylation, the ISR and the induction of pro-inflammatory cytokines in human THP1 macrophages submitted to oxidative stress and toll-like receptor (TLR) agonist. Similarly, luteolin inhibits induction of pro-inflammatory cytokines in murine microglial macrophages. In contrast, luteolin increased activation of the inflammasome, in a PKR-independent manner. Collectively, these data delineate the importance of PKR in the inflammation process to the ISR and induction of pro-inflammatory cytokines. Pharmacological inhibitors of PKR should be used in combination with drugs targeting directly the inflammasome.

Aims: So far, a total of five patients with eclipsed mitral regurgitation (MR) have been reported in the literature by three different teams. The aim of this article was to detail clinical and echocardiographic characteristics, and outcome of patients presenting eclipsed MR., Methods and Results: We defined eclipsed MR as spontaneous appearance, at rest, from 1 min to the next of an acute restriction in the motion of mitral leaflets preventing coaptation and leading to massive MR in patients with normal left ventricular end-diastolic diameter, left ventricular ejection fraction >45%, and baseline MR ≤2. Spontaneous regression occurred within 30 min, and no obvious trigger such as acute hypertension, new-onset arrhythmia, or myocardial ischaemia is present. Clinical data, ECG, echocardiographic data, surgery report, and follow-up status of six patients with eclipsed MR are reported: all were post-menopausal women with median age of 74 [57-80] years presenting hypertension (4/6), chronic kidney disease (5/6), or chronic anaemia (4/6). Five out of six patients experienced acute pulmonary oedema requiring hospitalization and underwent mitral valve replacement because of heart failure recurrence. Two patients died in the first days after surgery while the three others are free of symptoms at, respectively, 56, 18, and 10 months follow-up., Conclusion: Eclipsed MR is a clinical and echocardiographic syndrome responsible for heart failure with preserved EF. It is presently underdiagnosed and should be evoked in cases of recurrent acute pulmonary oedema without obvious trigger, in particular in patients presenting discordant evaluation of MR severity over time., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Defects involving several aesthetic subunits (ASUs) or lying at the junction of an ASU are challenging and require a complex reconstruction. This study aimed to describe the hemi-tip as a new ASU., Material and Methods: We conducted a retrospective study including patients who underwent a nasal reconstruction for lower nasal pyramid defects according to our modified ASU principle. Patients who suffered from a subtotal alar defect, which also involved <50% of the tip, were reconstructed after excising the remaining tissue of the hemi-tip subunit. An aesthetic evaluation was performed using a patient satisfaction scale and by independent raters., Results: From 2010 to 2014, 21 patients underwent a lower hemi-nose reconstruction. All patients had a full-thickness defect and underwent a reconstruction of the three layers of the nose. Sixty-four percent of our patients were very satisfied, 26% were satisfied, and only 10% were unsatisfied with their nasal tip appearance, with a mean score of 4.4/5. The nasal tip was also rated by independent raters with a mean score of 4.1/5., Discussion: Our results and experience showed that a midline scar between the two hemi-tips is inconspicuous. The majority of the defects involving only one side of the tip would benefit from the hemi-tip ASU reconstruction., Conclusion: We have modified the number of ASUs by considering the hemi-tip as a proper subunit., (Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10(-8) ). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Due to the increasing number of fat grafting procedures, several laboratories have developed their own fat processing system (Puregraft(®), LipiVage(®), Viafill(®), etc.), such as closed harvesting systems, centrifugation or washing and filtration devices, or even simple decantation techniques. However, all these tissue-engineering systems are expensive. Our team has developed a simple and fast autologous fat grafting system, useable even for a large volume of lipofilling, and based on low-pressure suction and a sterile closed-system for processing the harvested fat tissue. It is a cost-effective system, as it only costs 9.28Eur (10.52USD) for a 500milliliters autologous fat graft procedure., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: After implant-based breast reconstruction, the nipple reconstruction technique must be carefully chosen, especially in patients with a history of radiotherapy. When the contralateral nipple is not available, using a classical dermal-fat local flap may lead to the implant exposure, and consequently, removal. We describe here a simple nipple reconstruction technique, using a strictly dermal local flap and evaluate its complication rate., Patients and Methods: All patients who underwent our technique for nipple reconstruction between January 2012 and April 2015 were included in this retrospective study. We described our surgical technique and noted the occurrence of postoperative complications., Results: Forty-nine nipples, in 47 patients with a history of radiotherapy, were reconstructed with our technique. The mean age was 53 years old (range 27-78 years old). The average time between radiotherapy and nipple reconstruction was 42.5 months (range from 4.6 to 274.8 months). The mean follow-up was 30.9 months (range from 6 to 47 months). No implant exposure occurred. Regarding the nipple flap, two partial flap loss and one infection occurred, the whole complication rate was 6.1%. Regarding nipple projection, it was quite low (between 2 and 5 mm) after 6 months, but remained stable., Conclusion: Our strictly dermal local flap technique for nipple reconstruction is a safe procedure and represents a good alternative to composite contralateral nipple graft in irradiated patients with an implant-based reconstructed breast., (Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Bilateral reduction mammaplasty (BRM) is a common procedure in plastic surgery. Our study aims to determine whether single-shot infiltration with ropivacaine during surgery reduces postoperative pain and decreases analgesic consumption., Methods: In a prospective and monocentric study, all women operated by a single senior plastic surgeon, for whom BRM had been performed were included. The same surgical technique was performed for all patients (a superior pedicle, wise-pattern BRM with a closed-suction drainage). During the first half first part of the study period, none of the patients received ropivacaine infiltration (control group) and during the second half, all the patients received this infiltration (ropivacaine group). Infiltration was performed with a 20 mL solution of ropivacaine per side. Analgesic consumption and pain intensity were recorded during hospitalization and following discharge., Results: Forty-nine patients were divided into two groups (29 in the ropivacaine group and 20 in the control group). The ropivacaine group had a significantly lower consumption than the control group on all analgesics (paracetamol, tramadol, nefopam and morphin) (P < 0.001). Pain measurement reflected significantly lower scores in the ropivacaine group, both at four hours and three days postoperatively (P < 0.001). This difference was no longer significant at day 7 postoperatively (P=0.147)., Conclusion: Single-shot ropivacaine infiltration during surgery reduces postoperative pain and decreases the analgesic consumption. With this peroperative infiltration, BRM can be performed with good pain control and moderate analgesic consumption, limiting side effects., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Melanomas are characterized by high metastatic potential, with regional lymph node representing the most frequent site of early dissemination in this disease. These regional lymph nodes also represent the primary site for differentiation of natural killer (NK) cells. Although blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic lymph node (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in patients with melanoma. Here, we report that M-LN contains 0.5% to 11% of CD56(bright) NK cells among CD45(+) hematopoietic cells present and that this cell population surrounds tumor cell clusters in M-LN. This NK cell population was characterized by expression of CD62L, chemokine receptors, and high levels of natural cytotoxicity receptors (NCR), NK group 2 D (NKG2D), and DNAX accessory molecule 1 (DNAM-1). Expression of NCR-NKp30 and NKG2D correlated negatively with percentages of tumor cells in M-LN. Interestingly, M-LN contained a unique subset of mature CD56(bright)CD16(+) NK cells displaying coregulated expression of NCR and NKG2D activating receptors. Ex vivo analyses suggested that M-LN-derived NK cells were inactive but could be activated by appropriate cytokine signals [interleukin (IL)-2 or IL-15], and could lyse metastatic melanoma cells in a highly efficient manner compared with blood-derived NK cells. Taken together, the results offer evidence that adjuvant immunotherapy that targets NK cells in M-LN for activation may improve treatment of patients with sentinel lymph node-positive melanoma.

The reconstruction of severe defects of the ankle and foot is a challenge. The ideal solution should combine a thin skin flap on the dorsum to allow shoe fitting and a muscle flap with a split-thickness skin graft on the weight-bearing area. Perforator-based thoracodorsal chimaeric flaps allow us to achieve these two goals with minimal donor-site morbidity. We present a reconstruction of an extended circumferential defect of the ankle with an exposed heel using a chimaeric thoracodorsal perforator flap with a serratus muscle flap. The skin flap was transferred on the dorsal foot, whereas the serratus anterior muscle was transferred on the exposed heel. Postoperative recovery was uneventful and the patient began full weight bearing after 3 months. Twelve months after reconstruction, natural shape and walking function were successfully achieved., (Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK) cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III-IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV) was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR) and Natural Killer Group 2D (NKG2D) receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46) by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.

Objective: To evaluate the performance of a one-step test detecting intact hCG and free β-hCG isoforms in the urine of pregnant women to diagnose an abnormal pregnancy., Design: Prospective study., Setting: Emergency gynecology departments in teaching hospitals., Patient(s): Five hundred twenty-six patients were enrolled, 272 who were not pregnant and 254 who were pregnant., Intervention(s) and Main Outcome Measure(s): Semiquantitative determination of intact urinary hCG of supposedly not pregnant and pregnant women with vaginal bleeding and/or vaginal pain between 5 and 8 weeks of amenorrhea., Result(s): The sensitivity and specificity of the urine test for diagnosing nonpregnancy were, respectively, 100% (252/252) and 100% (272/272). The sensitivity and specificity of the urine test for diagnosing ectopic pregnancy (EP) were, respectively, 97% (32/33) and 83% (142/171). The negative predictive value is 99.3% (142/143). The sensitivity and specificity or the urine test for diagnosing miscarriage were, respectively, 89.6% (43/48) and 83% (142/171). The negative predictive value is 96.6% (142/147)., Conclusion(s): Abnormal pregnancy, such as an EP or a miscarriage, can be rapidly detected with the one-step test for intact hCG and free β-hCG isoforms. If ultrasound cannot confirm the localization and/or evolution of a pregnancy, using this test reduces medical supervision and repeated quantification of hCG., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

We conducted surveys in 1997 and 2002 to determine the rate, underlying sources and outcome of nosocomial bacteraemia. Blood culture results were reviewed daily. All patients with positive cultures drawn >or=48 h after hospitalization were included in the study and their charts were reviewed. The underlying source of infection was determined by pre-defined clinical and/or microbiological criteria. Patients were followed until discharge or death. In 1997 and 2002, 851 and 857 patient-unique cases of bacteraemia were diagnosed, respectively, excluding contaminants; of these, 228 (27%) and 277 (32%) cases, respectively, were hospital acquired (P<0.05). The overall rate decreased from 7.5 to 7.0 per 1,000 admissions (P<0.001). The sources of bacteraemia in 1997 and 2002, respectively, were: intravascular catheters (36% and 27%, P<0.05), urinary tract (8% and 15%, P<0.05), respiratory tract (5% and 13%, P<0.01) and surgical sites (14% and 4%, P<0.001). In one-third of patients, the source of bacteraemia could not be determined. Only 52% and 54%, respectively, of these patients were discharged alive (difference was not significant). In 1997, Staphylococcus aureus was the most frequent isolate (26%), followed by coagulase-negative Staphylococcus (13%) and Klebsiella pneumoniae (11%). By 2002, the incidence of S. aureus had fallen to 11% (P<0.001), acinetobacter was the single most frequently isolated organism (increased from 6% to 17%) (P<0.001). In-hospital mortality associated with acinetobacter bacteraemia (57%) was significantly higher than that for other organisms (31-43%) (P<0.05). In conclusion, prospective surveys of nosocomial bacteraemias provide valuable information, facilitating the pursuit of successful interventions.

Objective: To evaluate digoxin pharmacokinetic parameters using Bayesian estimation in 60 patients, and to identify factors that appeared to affect the risk of digoxin toxicity., Patients and Methods: 60 patients with serum digoxin concentrations were evaluated retrospectively. We collected demographic, clinical and laboratory data, and information on concurrent medications and clinical and electrocardiographic features of digoxin toxicity. The incidence of digoxin toxicity was evaluated in 50 patients. Serum digoxin concentrations were measured with fluorescence polarisation immunoassay Individual pharmacokinetic parameters were estimated by Bayesian method using Abbottbase Pharmacokinetic Systems., Results: Signs of digoxin toxicity were present in 23 patients (46%). Patients without signs of digoxin toxicity had a significantly lower mean serum digoxin concentration than patients with signs, 1.99 ± 0.9 μg/L vs 2.7 ± 1.5 μ.g/L, respectively (p = 0.047). Patients with serum digoxin concentrations >2.2 μg/L differed significantly from those with values ≤2.2 μg/L, respectively, for the following parameters: age (82.0 ± 8.0 vs 72.0 ± 16.0 years; p = 0.005), serum creatinine levels (133.0 ± 55.0 vs 106.0 ± 26.0 μmo1/L; p = 0.012), bodyweight (57.4 ± 12.8 vs 69.2 ± 17.8kg; p = 0.01), volume of distribution (208.5 ± 89.5 vs 315.7 ± 91.2L; p = 0.0001), total clearance (1.60 ± 0.65 vs 3.4 ± 1.5 L/h; p = 0.0001), and elimination half-life (94.2 ± 28.6 vs 72.4 ± 16.7h; p = 0.001). Estimation of optimal dose showed that the doses recommended in intoxicated patients should be 3.5 times lower to reach the therapeutic range., Conclusion: Digoxin concentrations were higher in patients with toxicity. Older age enhanced the risk of digoxin toxicity. Monitoring digoxin concentrations may help to confirm suspected digitalis toxicity.