[Case report of a cystic lung disease: From a rarity to the discovery of an unknown genetic variant]. / À propos d'un cas clinique de maladie kystique pulmonaire : d'une rareté à la découverte d'un variant génétique inconnu.

INTRODUCTION: Cystic lung diseases are rare, with numerous differential diagnoses. Iconographic discovery consequently necessitates medical examinations in view of proposing an etiological orientation. CASE REPORT: A 57-year-old woman consulted in pulmonology following fortuitous detection of a cystic lung disease on an abdominal CT scan. Complementary medical examinations did not allow orientation towards a particular diagnosis. During a follow-up consultation, the patient informed her pulmonologist of the recent detection of a monoallelic variant of a FAT4 gene in one of her daughters, who was suffering from edema of the lower limbs secondary to a disease of the lymphatic system. As our patient had a similar history, she likewise received a genetic analysis. A monoallelic variant not described in the genetic databases was observed, and considered as a probable pathogenic variant (class 4/5 on the pathogenicity scale of genetic variants). CONCLUSION: After analyzing the available literature data, we raise questions about a possible link between this variant of the FAT4 gene, chronic lymphedema and our patient's cystic lung disease.

Supraorbital transciliary approach as primary route to fronto-basal high grade glioma resection with 5-Aminolevulinic Acid use: Technical note.

BACKGROUND: Gliomas are diffuse intra-axial lesions, which can be accessed by multiple surgical corridors for a same location depending on the surgeon's preference. 5-Aminolevulinic Acid use facilitates the extend of resection in case of high-grade gliomas, especially when differentiating normal brain from tumor periphery is challenging. METHODS: Complete resection of glioblastoma via a supraorbital transciliary approach with 5-Aminolevulinic Acid use was performed without any complications, as demonstrated on postoperative MRI. RESULTS: Patient was discharged on the third postoperative day. Wound follow-up shows good cosmetic result. Patient underwent concomitant chemo-radiation (Temozolomide- 60Gy) and adjuvant chemotherapy (Temozolomide). No tumor recurrence was noted at six months follow-up. CONCLUSION: In selected cases, supraorbital transciliary approach could be proposed as primary approach as it provides the advantage of full control over all the vasculo-nervous structures at skull base without the necessity of protective brain retractor use while the 5-Aminolevulinic Acid use allows a gross total resection.

Formation of intracellular vesicles within the Gram+ Lactococcus lactis induced by the overexpression of Caveolin-1ß.

BACKGROUND: Caveolae are invaginated plasma membrane domains of 50-100 nm in diameter involved in many important physiological functions in eukaryotic cells. They are composed of different proteins, including the membrane-embedded caveolins and the peripheric cavins. Caveolin-1 has already been expressed in various expression systems (E. coli, insect cells, Toxoplasma gondii, cell-free system), generating intracellular caveolin-enriched vesicles in E. coli, insect cells and T. gondii. These systems helped to understand the protein insertion within the membrane and its oligomerization. There is still need for fundamental insights into the formation of specific domains on membrane, the deformation of a biological membrane driven by caveolin-1, the organization of a caveolar coat, and the requirement of specific lipids and proteins during the process. The aim of this study was to test whether the heterologously expressed caveolin-1ß was able to induce the formation of intracellular vesicles within a Gram+ bacterium, Lactococcus lactis, since it displays a specific lipid composition different from E. coli and appears to emerge as a good alternative to E. coli for efficient overexpression of various membrane proteins. RESULTS: Recombinant bacteria transformed with the plasmid pNZ-HTC coding for the canine isoform of caveolin-1ß were shown to produce caveolin-1ß, in its functional oligomeric form, at a high expression level unexpected for an eukaryotic membrane protein. Electron microscopy revealed several intracellular vesicles from 30 to 60 nm, a size comparable to E. coli h-caveolae, beneath the plasma membrane of the overexpressing bacteria, showing that caveolin-1ß is sufficient to induce membrane vesiculation. Immunolabelling studies showed antibodies on such neo-formed intracellular vesicles, but none on plasma membrane. Density gradient fractionation allowed the correlation between detection of oligomers on Western blot and appearance of vesicles measurable by DLS, showing the requirement of caveolin-1ß oligomerization for vesicle formation. CONCLUSIONS: Lactococcus lactis cells can heterologously overexpress caveolin-1ß, generating caveolin-1ß enriched intracellular neo-formed vesicles. These vesicles might be useful for potential co-expression of membrane proteins of pharmaceutical interest for their simplified functional characterization.

Cerebral arterio-venous malformations hemodynamics changes in hereditary hemorrhagic telangiectasia - case report.

BACKGROUND: Spontaneous obliteration of cerebral arteriovenous malformations (AVMs) is a rare phenomenon. Hereditary Hemorrhagic Telangiectasia (HHT) is a predisposal genetic condition for AVMs development in all organs. CASE ILLUSTRATION: We report the case of a 34 years old woman with HHT family history. After radiosurgical treatment of a symptomatic evolving cerebellar AVM, late control subtracted digital angiography (DSA) demonstrated the complete obliteration of this AVM but also spontaneous obliteration of 3 fronto-parietal AVMs without any hemorrhagic sign on MRI. CONCLUSION: To our knowledge, this is the first report of spontaneous obliteration of multiple and unruptured AVMs in a HTT case.

Is malignant edema and hemorrhage after occlusion of high-flow arteriovenous malformation related to the size of feeding arteries and draining veins?

OBJECTIVE: Our study aimed to identify predictive factors for malignant post-treatment edema and hemorrhage in patients who underwent microsurgical treatment of arteriovenous malformation (AVM) in our institution. METHODS: The study included 72 patients treated by microsurgery for cerebral symptomatic and/or ruptured AVM between 2010 and 2020. Six patients developed postprocedural malignant edema and hemorrhage (group M); the other 66 patients had no malignant edema and hemorrhage (group NM). In each patient, flow was assessed indirectly by summing the diameters of all feeding arteries to obtain an overall diameter (ODA), and similarly for draining veins (ODV). High-flow was defined as a delay between feeding artery injection and draining vein injection (DAV)<1 second on dynamic digital subtraction angiography. Univariate analysis was performed. RESULTS: Mean ODA and ODV were respectively 11mm (±8.2) and 11mm (±5.3) in group M and 2.9mm (±1.4) and 3.7mm (±1.3) in group NM (P=0.001). High-flow AVM was demonstrated in 4 out of 5 patients (85%) in group M and in 14 out of 55 (25%) in group NM (P=0.02). Associated aneurysm was seen in 5 patients in group M (83%) and in 11 in group NM (17%) (P=0.001). CONCLUSION: High-flow AVM may be associated with higher risk of postoperative edema and hemorrhage. Multidisciplinary discussion is mandatory in these cases, to define a pre-therapeutic plan for progressive staged vascular malformation occlusion.

Spontaneous disappearance of brain arteriovenous malformation: A case series.

OBJECTIVE: Brain arteriovenous malformation (BAVM) is defined as abnormal communication between cerebral of arteries and veins, without capillaries. Clinically, it may involve intracranial hemorrhage or seizures. Complete spontaneous resolution, known as BAVM disappearance, has been reported in rare cases. METHODS: We retrospectively collated all cases of BAVM in Lille University Hospital, from 2005 to 2018, and identified all cases of spontaneous BAVM disappearance on angiography (nidus and early venous drainage). RESULTS: There were 4 cases of spontaneous BAVM disappearance, in 3573 patients: i.e., prevalence of 0.1%. Sex ratio was 2:2; ages ranged from 14 to 46 years; nidus size was generally small (<20mm); 3 of the 4 patients had superficial venous drainage. Revelation of BAVM was by hemorrhage in 3 cases and by seizure in 1. There were no cases of recanalization at 1 year's follow-up. CONCLUSION: Spontaneous BAVM disappearance is rare. Associated factors may include small nidus, superficial venous drainage and hemorrhage.

Manual Lymphatic Drainage Increases the Number of Opened Lymphatic Pathways in Patients with Lower Limb Lymphedemas: A Sequential Research on 80 Patients.

The purpose of this study was to lymphoscintigraphically assess the effect of skin mobilization, nonspecific massage, and manual lymphatic drainage (MLD) on the root of the lower limb in patients with lower limb lymphedema. Lower limb root lymphoscintigraphical exams of 80 patients with lower limb lymphedema were analyzed. All patients underwent our stand 3 phase protocol and then were subjected to the 4th phase which included 3 subphases. Images were taken directly after the injection (subphase 1), after pinching and stretching the injection site (subphase 2), after nonspecific massage was applied to the injected site (subphase 3) and after manual lymphatic drainage of the injected site (subphase 4). The number of opened lymphatic pathways was analyzed and compared after and between each subphase (SP). SP 1 displayed open lymphatic pathways in 22 of the 80 cases (27.5%). SP 2 displayed newly opened lymphatic pathways in 48 of the 80 cases (60.0%). SP 3 displayed newly opened lymphatic pathways in 57 of the 80 cases (71.3%). Only 9 of these 57 cases did not show improvement following the next SP. SP 4 displayed newly opened lymphatic pathways in 60 of the 80 cases (75.1%). MLD improved the visualization of the lymphatic pathways in 48 cases (60%) compared to phase 3. MLD was the only technique to allow visualization of the lymphatic drainage at the level of the root of the edematous limb in 6 cases (7.5%). Physical therapy leads to a greater number of lymphatic collaterals opening in a region where no other complex decongestive therapy technique can be applied.

Mutations in NBAS and SCYL1, genetic causes of recurrent liver failure in children: Three case reports and a literature review.

Acute liver failure (ALF) in childhood is a life-threatening emergency. ALF is often caused by drug toxicity, autoimmune hepatitis, inherited metabolic diseases, and infections. However, despite thorough investigations, a cause cannot be determined in approximately 50% of cases. Here, we report three cases with recurrent ALF caused by NBAS and SCYL1 pathogenic variants. These patients did not present with any other phenotypic sign usually associated with NBAS and SCYL1 pathogenic variants. Two of them underwent liver transplantation and are healthy without recurrence of ALF. We propose NBAS and SCYL1 genetic analysis in children with unexplained fever-triggered recurrent ALF even without a typical phenotype.

Sensitive skin can be small fibre neuropathy: results from a case-control quantitative sensory testing study.

BACKGROUND: Sensitive skin syndrome (SSS) is defined as the occurrence of unpleasant sensations (itch, pain, burning, prickling) in response to stimuli that should not normally cause such sensations. Previous studies show that SSS could be a small fibre neuropathy, but quantitative sensory testing (QST) is lacking. OBJECTIVES: Using QST, to determine the presence or absence of tactile sensitivity disorder, mainly heat pain threshold (HPT), in patients with SSS. METHODS: This monocentric case-control study included 21 patients with SSS and 21 controls. The patients underwent QST. Neuropathic pain was assessed by two questionnaires: the Douleur Neuropathique 4 (DN4) and the Neuropathic Pain Symptom Inventory (NPSI). RESULTS: Forty-two patients were included in the study. The HPT was significantly lower in the cases (14·5 ± 2·8) than in the controls (17·8 ± 2·5) (P < 0·001). Intermediate pain (HPT 5·0) was also significantly decreased in patients with SSS. The DN4 and NPSI scores were significantly higher in the cases than in the controls. CONCLUSIONS: The decrease in HPT in patients with SSS compared with controls suggests the presence of hyperalgesia, probably due to the damage of C-fibres. These findings, as well as the increased DN4 and NPSI scores, strengthen the neuronal hypothesis of SSS and are new arguments for consideration of SSS as small fibre neuropathy.

Aggregate exposure to common fragrance compounds: Comparison of the contribution of essential oils and cosmetics using probabilistic methods and the example of limonene.

The knowledge of aggregate exposure to different types of products is paramount in the risk assessment. The aim of this study was to compare the relative contribution of essential oils compared to cosmetics on the daily dermal exposure to limonene, an ubiquitous fragrance compound that can be an allergen depending on its degree of oxidation. Aggregate daily exposure to limonene was calculated among a panel of French volunteers using both essential oils and cosmetics, for 4 different specific zones, i.e. face and neck, chest, upper limbs and lower limbs. Calculations were made using a probabilistic Monte Carlo method and sensitivity analysis. The main strength of this work was the inclusion of essential oils in addition to cosmetics in the model. For the first time, the generated data could be used to compare the contribution of these two products in dermal exposure. Essential oils appear to be significant contributors to exposure to limonene particularly for the face. This work is a first step that will permit to determine the exposure to other fragrance compounds with sensitizing potential. These data will be useful for risk managers to consider the inclusion of essential oils in the overall burden of this pathology.

Noise characterization of analog to digital converters for amplitude and phase noise measurements.

Improvements on electronic technology in recent years have allowed the application of digital techniques in phase noise metrology, where low noise and high accuracy are required, yielding flexibility in system implementation and setup. This results in measurement systems with extended capabilities, additional functionalities, and ease of use. In most digital schemes, the Analog to Digital Converters (ADCs) set the ultimate performance of the system; therefore the proper selection of this component is a critical issue. Currently, the information available in the literature describes in depth the ADC features only at frequency offsets far from the carrier. However, the performance close to the carrier is a more important concern. As a consequence, the ADC noise is, in general, analyzed on the implemented phase measurement setup. We propose a noise model for ADCs and a method to estimate its parameters. The method retrieves the phase modulation and amplitude modulation noise by sampling around zero and maximum amplitude, a test sine-wave synchronous with the ADC clock. The model allows discriminating the ADC noise sources and obtaining the phase noise and amplitude noise power spectral densities from 10 Hz to one half of the sampling frequency. This approach reduces the data processing, allowing an efficient ADC evaluation in terms of hardware complexity and computational cost.

Indocyanine green fluorescence-guided surgery after IV injection in metastatic colorectal cancer: A systematic review.

OBJECTIVE: Indocyanine green fluorescence-guided surgery (ICG-FGS) has emerged as a potential new imaging modality for improving the detection of hepatic, lymph node (LN), and peritoneal metastases in colorectal cancer (CRC) patients. The aim of this paper is to review the available literature in the clinical setting of ICG-FGS for tumoral detection in various fields of metastatic colorectal disease. METHODS: PubMed and Medline literature databases were searched for original articles on the use of ICG in the setting of clinical studies on colorectal cancer. The search terms used were "near-infrared fluorescence", "intraoperative imaging", "indocyanine green", "human" and "colorectal cancer". RESULTS: ICG fluorescence imaging (ICG-FI) is clearly supported as an intraoperative technique that allows the detection of additional superficial hepatic metastases of CRC. Data on the role of ICG-FI in the intraoperative detection of peritoneal metastases and LN metastases are scarce but encouraging and ICG-FI could potentially improve the staging and treatment of these patients. CONCLUSION: ICG-FI is a promising imaging technique in the detection of small infraclinic LN, hepatic, and peritoneal metastatic deposits that may allow better staging and more complete surgical resection with a potential prognostic benefit for patients.

Grade 1 Spetzler and Martin cerebral ruptured arteriovenous malformations treated by microsurgery: Poor functional outcome is related to injury from haemorrhage.

INTRODUCTION: Ruptured arteriovenous malformations (rAVM) are life-threatening diseases. OBJECTIVE: To evaluate the outcome of patients with grade 1 SPM rAVM after microsurgical treatment. MATERIALS AND METHOD: We retrospectively included 64 consecutive operated patients with a grade 1 SPM rAVM in our institution between 2002 and 2012. Complications related to the surgical procedure were recorded. All patients were re-evaluated 3months after treatment using the modified Rankin Scale score (mRS). Persistent neurological disorders were evaluated 1year after bleeding. Conventional cerebral angiography was performed for each patient immediately after surgical treatment and 1year later. RESULTS: The mean age at diagnosis was 30.8 years. Initial WFNS score was grade 1 in 25 patients, grade 2 in 11 patients, grade 3 in 10 patients, grade 4 in 9 patients and grade 5 in 9 patients. No remnant was left and a new surgery was performed only in a single patient who was initially operated-on under emergency conditions with limited preoperative investigations due to a poor clinical grade. Early postoperative complications related to the surgical procedure were recorded in 7 patients. The mRS score 3months after treatment was ≤2 in 53 patients (83%). Persistent neurological disorders were recorded in 40 patients (62.5%). High initial WFNS score (>2) and the hydrocephalus were significantly associated (P<0.05) to a bad functional outcome (mRS>2). CONCLUSION: Grade 1 rAVM is a life-threatening disease concerning in most cases young patients. Long-term morbidity is often related to the hemorrhagic brain damage and rarely to the AVM resection.

[Next-generation DNA sequencing in clinical diagnostics]. / Le séquençage d'ADN à haut débit en pratique clinique.

The advent of next generation sequencing (NGS) technologies is so scale-changing that it modifies molecular diagnostics indications and induces laboratories to rethink their diagnostic strategies, until now based on the Sanger sequencing routine. Several high-throughput approaches are available from the sequencing of a gene panel, to an exome, or even a genome. In all cases, a tremendous amount of data is generated, which has to be filtered, interpreted and analyzed using powerful bioinformatics tools. In parallel, ethical considerations are raised to avoid the potential drifts of these powerful approaches. In all medical fields, and particularly in pediatrics, this new strategy offers better efficacy and faster mutation identification, allowing better support and care for patients and their families and even improving genetic counseling. In the present paper, we discuss the different NGS-based approaches and strategies as well as the issues involved in these new technologies applied to molecular diagnosis of rare diseases. Altogether, rare diseases affect more than 3 million people in France and are responsible for about one-third of childhood deaths.

Vertebral artery-posterior inferior cerebellar artery convergence aneurysms treated by endovascular or surgical treatment: Mid- and long-term outcome.

INTRODUCTION: Management of vertebral artery-posterior inferior cerebellar artery convergence (VA-PICA) saccular aneurysms requires a specialized neurovascular team. The objective is to preserve the functional outcome while performing a complete and reliable long-term exclusion of the aneurysm. OBJECTIVE: The aim of our study was to evaluate the outcome of patients with VA-PICA saccular aneurysms after treatment. MATERIALS AND METHODS: This was a retrospective series of 21 consecutive patients with a VA-PICA saccular aneurysm treated between 2000 and 2012 at our institution. Treatment option (endovascular or microsurgical) was decided for each patient following a multidisciplinary discussion. RESULTS: Twenty-one patients were treated for a VA-PICA saccular aneurysm including 16 for a ruptured aneurysm and 5 for an asymptomatic aneurysm. Among all patients, 11 underwent endovascular treatment and 10 had microsurgical treatment. Our results showed a major aneurysm recurrence after endovascular treatment in 3 patients that required a further endovascular treatment in 2 cases. These 3 major recurrences occurred after treatment of a ruptured aneurysm when the initial angiography demonstrated the origin of the PICA at the neck of the aneurysm. After microsurgery, angiography showed a remnant neck in 2 patients including 1 treated by further endovascular procedure. CONCLUSION: VA-PICA aneurysms are rare and require multidisciplinary management. Microsurgical treatment should be discussed when the PICA originates from the aneurysmal neck, particularly in patients with a ruptured small aneurysm, in order to obtain a reliable and long-term exclusion of the aneurysm.

Consumption of hair dye products by the French women population: Usage pattern and exposure assessment.

Only few published data are available in the literature about consumption and exposure, for hair dye products. The aim of this study was to assess the use of 10 different hair dye products in French Women with a focus on consumption of hair dye in different places of use (at home and at the hairdressers) in order to assess the corresponding dermal exposures. The assessment was performed on a total of 4237 women older than 15 years old, thanks to three national web surveys. The percentage of hair dye users among the French women population was about 64%.The mean frequency of use ranged between 2.23 and 14.22 times per year depending on the studied product and age category of women. This study provided the first data available for exposure to hair dye products with mean exposures ranging between 1.48 and 6.49 mg/kg bw/day depending on the product studied and age category of women. Moreover, consumption data obtained in this study might be useful to perform safety assessment of hair dye products thanks to the knowledge of the age categories of the population having the highest percentage of users and/or frequency of use.

Fluorescence imaging after intraoperative intravenous injection of indocyanine green for detection of lymph node metastases in colorectal cancer.

PURPOSE: This short communication aims at reporting the potential role of ICG fluorescence imaging after an intraoperative IV injection in the detection of lymph nodes (LNs) of a colorectal cancer origin. PATIENTS AND METHODS: Two patients who were included in a protocol study evaluating the role of ICG in the detection of peritoneal metastases of colorectal origin (Protocol NCT-01995591) also had fluorescent LNs at exploration with a dedicated near-infrared camera system (Photodynamic Eye, PDE; Hamamatsu Photonics, Hamamatsu, Japan). An IV injection of ICG was delivered intraoperatively at 0.25 mg/kg. All LNs were also explored for their fluorescence, and tumor to background ratio (TBR) was calculated with IC-Calc 2.0 program. RESULTS: One patient had two retroperitoneal lymph node metastases and one mesocolic on a pre-operative work-up. The three tumoural lymph nodes at histopathology were hyperfluorescent in comparison to other uninvolved LNs. One patient had no pre-operatively known LN metastases and had one epigastric hyperfluorescent LN discovered at intraoperative exploration. This LN of 6 mm in size was malignant at histopathology. CONCLUSION: This is the first report about tumoural LN of colorectal cancer origin detected by fluorescence imaging with intraoperative IV free-ICG injection. ICG fluorescence imaging by intraoperative IV injection represents an easy method for detecting metastatic LNs in colorectal cancer. This proof of concept should lead to further research in this field.