Terrorist attacks in Paris: Surgical trauma experience in a referral center.

BACKGROUND: On November 13th, 2015, terrorist bomb explosions and gunshots occurred in Paris, France, with 129 people immediately killed, and more than 300 being injured. This article describes the staff organization, surgical management, and patterns of injuries in casualties who were referred to the Teaching European Hospital Georges Pompidou. METHODS: This study is a retrospective analysis of the pre-hospital response and the in-hospital response in our referral trauma center. Data for patient flow, resource use, patterns of injuries and outcomes were obtained by the review of electronic hospital records. RESULTS: Forty-one patients were referred to our center, and 22 requiring surgery were hospitalized for>24h. From November 14th at 0:41 A.M. to November 15th at 1:10 A.M., 23 surgical interventions were performed on 22 casualties. Gunshot injuries and/or shrapnel wounds were found in 45%, fractures in 45%, head trauma in 4.5%, and abdominal injuries in 14%. Soft-tissue and musculoskeletal injuries predominated in 77% of cases, peripheral nerve injury was identified in 30%. The mortality rate was 0% at last follow up. CONCLUSION: Rapid staff and logistical response, immediate access to operating rooms, and multidisciplinary surgical care delivery led to excellent short-term outcomes, with no in-hospital death and only one patient being still hospitalized 45days after the initial event.

The value of a rapid contrast-enhanced angio-MRI protocol in the detection of head and neck paragangliomas in SDHx mutations carriers: a retrospective study on behalf of the PGL.EVA investigators.

OBJECTIVES: To assess the performance of a simplified MRI protocol consisting of a contrast-enhanced three-dimensional MR angiography (CE-MRA) in association with a post-contrast T1-weighted sequence (T1WIV) for the detection of HNPGLs in SDHx mutation carriers. METHODS: This retrospective sub-study is based on the multicenter PGL.EVA cohort, which prospectively enrolled SDHx mutation carriers from 2005 to 2009; 157 index cases or relatives were included. CE-MRA and the T1WIV images were read solely with knowledge of the clinical data but blind to the diagnosis. Sensitivity, specificity and likelihood ratios for the simplified MRI protocol were compared to the full MRI protocol reading results and to the gold standard status obtained through the consensus of an expert committee. RESULTS: The sensitivity and specificity of the readings of the simplified MRI protocol were, respectively, 88.7 % (95 % CI = 78.1-95.3) and 93.7 % (95 % CI = 86.8-97.7) versus 80.7 % (95 % CI = 68.6-89.6) and 94.7 % (95 % CI = 88.1-98.3) for the readings of the full MRI protocol. CONCLUSIONS: The simplified post-contrast MRI with shorter duration (5 to 10 minutes) showed no performance difference compared to the lengthy standard full MRI and can be proposed for the detection of head and neck paragangliomas (HNPGLs) in SDHx mutation carriers. KEY POINTS: • Rapid angio-MRI protocol and the usual lengthy protocol show equal diagnostic performance. • The CE-MRA is the key sequence for the detection of HNPGLs. • The T1WIV sequence assists in localizing HNPGLs.

In Vivo Detection of Succinate by Magnetic Resonance Spectroscopy as a Hallmark of SDHx Mutations in Paraganglioma.

PURPOSE: Germline mutations in genes encoding mitochondrial succinate dehydrogenase (SDH) are found in patients with paragangliomas, pheochromocytomas, gastrointestinal stromal tumors, and renal cancers. SDH inactivation leads to a massive accumulation of succinate, acting as an oncometabolite and which levels, assessed on surgically resected tissue are a highly specific biomarker of SDHx-mutated tumors. The aim of this study was to address the feasibility of detecting succinate in vivo by magnetic resonance spectroscopy. EXPERIMENTAL DESIGN: A pulsed proton magnetic resonance spectroscopy ((1)H-MRS) sequence was developed, optimized, and applied to image nude mice grafted with Sdhb(-/-) or wild-type chromaffin cells. The method was then applied to patients with paraganglioma carrying (n = 5) or not (n = 4) an SDHx gene mutation. Following surgery, succinate was measured using gas chromatography/mass spectrometry, and SDH protein expression was assessed by immunohistochemistry in resected tumors. RESULTS: A succinate peak was observed at 2.44 ppm by (1)H-MRS in all Sdhb(-/-)-derived tumors in mice and in all paragangliomas of patients carrying an SDHx gene mutation, but neither in wild-type mouse tumors nor in patients exempt of SDHx mutation. In one patient, (1)H-MRS results led to the identification of an unsuspected SDHA gene mutation. In another case, it helped define the pathogenicity of a variant of unknown significance in the SDHB gene. CONCLUSIONS: Detection of succinate by (1)H-MRS is a highly specific and sensitive hallmark of SDHx mutations. This noninvasive approach is a simple and robust method allowing in vivo detection of the major biomarker of SDHx-mutated tumors.

Imaging work-up for screening of paraganglioma and pheochromocytoma in SDHx mutation carriers: a multicenter prospective study from the PGL.EVA Investigators.

CONTEXT: Recommendations have not been established concerning imaging to screen SDHx mutation carriers for paraganglioma and pheochromocytoma. OBJECTIVE: Our objective was to compare the performance of gadolinium-enhanced magnetic resonance angiography, contrast-enhanced computed tomography, and [(123)I]metaiodo-benzylguanidine and somatostatin receptor scintigraphies for detecting head and neck and thoracic-abdominal-pelvic paragangliomas in SDHx mutation carriers. DESIGN AND SETTING: We conducted a prospective, multicenter study from June 2005 to December 2009 at 23 French medical centers. PATIENTS: A total of 238 index cases or relatives carrying mutations in SDHD, SDHB, or SDHC genes were included. INTERVENTION: Images obtained by each technique were analyzed blind, without knowledge of results from other tests, first in each local center and then centrally. MAIN OUTCOME MEASURES: We evaluated sensitivity, specificity, and likelihood ratios for individual and combinations of tests, the gold standard being the consensus of an expert committee. RESULTS: Two hundred two tumors were diagnosed in 96 subjects. At local assessment, the sensitivity of anatomical imaging for detecting all tumors was higher (85.7%) than that of both scintigraphic techniques (42.7% for [(123)I]metaiodo-benzylguanidine and 69.5% for somatostatin receptor scintigraphy), except for thoracic localizations where somatostatin receptor scintigraphy was more sensitive (61.5 vs. 46.2% for anatomical imaging and 30.8% for [(123)I]metaiodo-benzylguanidine scintigraphy). The best diagnostic performance during local assessment was obtained by combining anatomical imaging tests and somatostatin receptor scintigraphy (sensitivity 91.7%). Central assessment significantly increased the sensitivity (98.6%) of tests in combination. CONCLUSIONS: In routine practice, the imaging work-up for screening SDHx mutation carriers should include thoraco-abdomino-pelvic computed tomography, head and neck magnetic angiography, and somatostatin receptor scintigraphy. Expert centralized image assessment is recommended.

Use of single MRI and 18F-FDG PET-CT scans in both diagnosis and radiotherapy treatment planning in patients with head and neck cancer: advantage on target volume and critical organ delineation.

BACKGROUND: The use of a single MRI and 18F-fluoro deoxyglucose positron emission tomography-CT (18F-FDG PET-CT) was evaluated, both in diagnostic procedure and radiotherapy planning, in patients with head and neck cancer. METHODS: Thirty-five patients with nasopharyngeal and oropharyngeal tumors were studied. The MRI and 18F-FDG PET-CT were used for both diagnostic work-up and gross tumor volume and critical structure delineation. The interobserver variation (IOV) of volumes determined on MRI and CT by a radiotherapist and by a radiologist were compared as well as their impact on dose distribution. RESULTS: The CT-MRI decreased the IOV of parotid glands in 12 of 35 and target volume in 15 of 35 patients. The use of 18F-FDG PET-CT changed the treatment design in 6 of 21 patients. CONCLUSIONS: Diagnostic imaging performed in the treatment position can improve the accuracy of radiotherapy planning in case of intracranial tumor extension, heavy dental work, or contraindication for contrast-enhanced CT, but not in the absence of these conditions.

Three new PAX6 mutations including one causing an unusual ophthalmic phenotype associated with neurodevelopmental abnormalities.

PURPOSE: The PAX6 gene was first described as a candidate for human aniridia. However, PAX6 expression is not restricted to the eye and it appears to be crucial for brain development. We studied PAX6 mutations in a large spectrum of patients who presented with aniridia phenotypes, Peters' anomaly, and anterior segment malformations associated or not with neurological anomalies. METHODS: Patients and related families were ophthalmologically phenotyped, and in some cases neurologically and endocrinologically examined. We screened the PAX6 gene by direct sequencing in three groups of patients: those affected by aniridia; those with diverse ocular manifestations; and those with Peters' anomaly. Two mutations were investigated by generating crystallographic representations of the amino acid changes. RESULTS: Three novel heterozygous mutations affecting three unrelated families were identified: the g.572T>C nucleotide change, located in exon 5, and corresponding to the Leucine 46 Proline amino-acid mutation (L46P); the g.655A>G nucleotide change, located in exon 6, and corresponding to the Serine 74 Glycine amino-acid mutation (S74G); and the nucleotide deletion 579delG del, located in exon 6, which induces a frameshift mutation leading to a stop codon (V48fsX53). The L46P mutation was identified in affected patients presenting bilateral microphthalmia, cataracts, and nystagmus. The S74G mutation was found in a large family that had congenital ocular abnormalities, diverse neurological manifestations, and variable cognitive impairments. The 579delG deletion (V48fsX53) caused in the affected members of the same family bilateral aniridia associated with congenital cataract, foveal hypolasia, and nystagmus. We also detected a novel intronic nucleotide change, IVS2+9G>A (very likely a mutation) in an apparently isolated patient affected by a complex ocular phenotype, characterized primarily by a bilateral microphthalmia. Whether this nucleotide change is indeed pathogenic remains to be demonstrated. Two previously known heterozygous mutations of the PAX6 gene sequence were also detected in patients affected by aniridia: a de novo previously known nucleotide change, g.972C>T (Q179X), in exon 8, leading to a stop codon and a heterozygous g.555C>A (C40X) recurrent nonsense mutation in exon 5. No mutations were found in patients with Peters' anomaly. CONCLUSIONS: We identified three mutations associated with aniridia phenotypes (Q179X, C40X, and V48fsX53). The three other mutations reported here cause non-aniridia ocular phenotypes associated in some cases with neurological anomalies. The IVS2+9G>A nucleotide change was detected in a patient with a microphthalmia phenotype. The L46P mutation was detected in a family with microphthalmia, cataract, and nystagmus. This mutation is located in the DNA-binding paired-domain and the crystallographic representations of this mutation show that this mutation may affect the helix-turn-helix motif, and as a consequence the DNA-binding properties of the resulting mutated protein. Ser74 is located in the PAX6 PD linker region, essential for DNA recognition and DNA binding, and the side chain of the Ser74 contributes to DNA recognition by the linker domain through direct contacts. Crystallographic representations show that the S74G mutation results in no side chain and therefore perturbs the DNA-binding properties of PAX6. This study highlights the severity and diversity of the consequences of PAX6 mutations that appeared to result from the complexity of the PAX6 gene structure, and the numerous possibilities for DNA binding. This study emphasizes the fact that neurodevelopmental abnormalities may be caused by PAX6 mutations. The neuro-developmental abnormalities caused by PAX6 mutations are probably still overlooked in the current clinical examinations performed throughout the world in patients affected by PAX6 mutations.

Identification of the first intragenic deletion of the PITX2 gene causing an Axenfeld-Rieger Syndrome: case report.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is characterized by bilateral congenital abnormalities of the anterior segment of the eye associated with abnormalities of the teeth, midface, and umbilicus. Most cases of ARS are caused by mutations in the genes encoding PITX2 or FOXC1. Here we describe a family affected by a severe form of ARS. CASE PRESENTATION: Two members of this family (father and daughter) presented with typical ARS and developed severe glaucoma. The ocular phenotype was much more severe in the daughter than in the father. Magnetic resonance imaging (MRI) detected an aggressive form of meningioma in the father. There was no mutation in the PITX2 gene, determined by exon screening. We identified an intragenic deletion by quantitative genomic PCR analysis and characterized this deletion in detail. CONCLUSION: Our findings implicate the first intragenic deletion of the PITX2 gene in the pathogenesis of a severe form of ARS in an affected family. This study stresses the importance of a systematic search for intragenic deletions in families affected by ARS and in sporadic cases for which no mutations in the exons or introns of PITX2 have been found. The molecular genetics of some ARS pedigrees should be re-examined with enzymes that can amplify medium and large genomic fragments.

Adrenal suppression and osteoporosis after treatment of nasal polyposis.

CONCLUSION: Patients with severe nasal polyposis (NP) and a high steroid consumption have a high prevalence of glucocorticoid-induced osteoporosis and secondary adrenal insufficiency. OBJECTIVES: To evaluate the risk of complications of the medical treatment in patients presenting with the diagnosis of NP. PATIENTS AND METHODS: This was a prospective study. A total of 46 consecutive patients with NP were included when the oral steroid consumption during the past year was greater than three short courses of systemic steroid treatment (i.e. more than 21 days per year of treatment, prednisolone 1 mg/kg body weight per day, for 6-10 days). The nasal function was checked on the basis of five criteria: nasal obstruction, anterior rhinorrhea, posterior rhinorrhea, facial pain, and loss of sense of smell. Two tests were carried out for each patient: (i) a bone mineral density evaluation by dual energy X-ray absorptiometry (DXA) at three different sites in the lumbar spine and femur, and (ii) an evaluation of the hypothalamic-pituitary-adrenal (HPA) axis by the synacthen test. RESULTS: Most of the patients had a severe NP associated with asthma (78.3% of the population), and aspirin idiosyncrasy (28.3%). In all, 10.9% and 43.5% of patients had osteoporosis and osteopenia at the lumbar spine site. Twenty patients (48.8% of the tested patients) had an asymptomatic adrenal insufficiency.

Pleomorphic adenoma of the nasal septum and its relationship with Epstein-Barr virus.

OBJECTIVES: Pleomorphic adenoma is the most common benign tumor of the major salivary glands, especially of the parotid gland. It is much less common in the minor salivary glands of the oral cavity, and it rarely occurs in others sites in the head and neck. Even if virus involvement in salivary glands tumor has been many times discuted, the etiology of this tumor keeps being unknown. As compared to other nasal tumors, we tried to prove if Epstein-Barr virus (EBV) could be involved in the development of pleomorphic adenoma in this particular nasal localization. METHODS: Three cases of pleomorphic adenomas of the nasal septum (two women and a man in age of 23-59 years) were retrospectively studied. All had positive rate of EBV-related blood antibodies. All the patients had undergone endoscopic surgery to remove the complete tumor. We used hybridation technique in the search for EBV-DNA in the three tumors. RESULTS AND CONCLUSION: We had positive EBV-DNA detection in the tumor in one case, which seemed to prove relationship between pleomorphic adenoma and this virus. The literature concerning the subject is reviewed in order to explain EBV involvement in the development of such tumors in this particular localization.

Chiari type I malformation in four unrelated patients affected with Fabry disease.

Fabry disease (FD) is an X-linked inborn error of metabolism resulting from the deficient activity of alpha-galactosidase A which leads to the widespread deposition of glycosphingolipids in lysosomes, and to ischemic complications involving kidneys, heart and brain. Among neurological symptoms, strokes and transient ischemic attacks (TIA) have been reported. A 30-year-old male patient, with FD, was referred to us for evaluation of a sudden episode of dizziness, with disequilibrium, and diplopia, in agreement with the diagnosis of a TIA. Head magnetic resonance imaging (MRI) showed no cerebrovascular involvement but revealed the presence of Chiari type I malformation (CMI). We subsequently performed head MRI in a cohort of 44 consecutive hemizygous male patients and seven heterozygous females affected with FD, and identified three additional cases (two males and one female) of CMI. Whether the association is coincidental or not will need further studies but our data suggest that CMI should be ruled out in all Fabry patients.

[Bone mineral density after treatment for nasal polyposis]. / Traitement médical de la polypose naso-sinusienne. Effet sur la densité minérale osseuse.

PURPOSE: Medical treatment of nasal polyposis is based on corticotherapy, and the most frequent complication of long-term corticotherapy is corticosteroid-induced osteoporosis. OBJECTIVE: To assess bone mineral density after long-term, high-dose corticosteroid treatment for nasal polyposis. PATIENTS AND METHODS: Bone mineral density at the spine and hip was measured by absorptiometry in 32 patients who had received high doses of corticosteroids for nasal polyposis. None of them had a disease that interfered with bone mineral density RESULTS: Bone mineral density was measured in 32 patients (59% men) aged 49.7 +/- 3.7 years [range: 29 - 74] after corticosteroid therapy for a mean of 5.3 years [range: 2-22 years]. More than 70% of the patients had abnormal bone density (osteopenia or osteoporosis ) at the spine and 44% at the hip. Only eight (25%) patients had normal bone density at both the spine and hip. CONCLUSION: High doses of corticosteroids in the treatment of nasal polyposis affect bone mineral density. Assessment of the benefits and risks of endoscopic sinus surgery must take this iatrogenic risk into account.

Correlation between nasosinusal symptoms and topographic diagnosis in chronic rhinosinusitis.

Rhinitis and sinusitis concern roughly a quarter of the population in the Western world. They are associated with a wide range of symptoms: nasal obstruction, anterior and posterior nasal discharge, sneezing episodes, facial pain or congestion, and taste and smell disorders. The aim of this prospective study was to evaluate the clinical significance of these various symptoms as a function of the topographic diagnosis of chronic rhinosinusitis. The study involved 474 patients with signs of chronic perennial and persistent rhinosinusitis. The disorders of the nasal cavities and paranasal sinuses were classified into three main diagnostic categories: chronic rhinitis, localized sinusitis (mainly, anterior sinusitis), and diffuse rhinosinusitis (ie, nasal polyposis). A principal components analysis was performed. The symptom patterns of the three main clinical entities differed greatly. Most of the following clinical signs--nasal obstruction, anterior and posterior nasal discharge, sneezing, and facial congestion--are found in all diagnostic categories and hold no specific clinical significance. By contrast, four symptoms seem to have a substantial differentiating potential: anosmia and complete loss of flavor for diffuse rhinosinusitis, cacosmia for localized anterior sinusitis, and severe facial pain for localized sinusitis. This study proposes a new analysis of the relationship between symptoms of chronic rhinosinusitis and findings on a sinus computed tomography scan.

Persisting reversed clock syndrome.

BACKGROUND: The reversed clock phenomenon results in the transposition of objects from one side to another. Its major manifestation consists in the reversal of clock numbers in clock-drawing test. It could be due to a stroke disrupting attentional cerebral network. This phenomenon usually regresses in a few days. OBJECTIVE: To report a case of reversed clock phenomenon with disorders of space representation that did not regress spontaneously. DESIGN: Case report. PATIENT: A 67 year-old woman was referred due to headaches associated with gait disorder, visual field deficit and disturbance of space representation. RESULTS: Magnetic resonance imaging demonstrates two right cerebral infarcts mainly localized in the parieto-occipital region. A week after her stoke, clinical testing confirms a reversed clock phenomenon. The patient placed the hands of a clock in the opposite direction of what was specified. She got lost at home locating rooms in directions opposite to their real ones. Rehabilitation sessions partially improved these manifestations. CONCLUSION: Although it usually improves in a few days, reversed clock phenomenon can persist longer. Rehabilitation sessions based on localization exercises may be helpful in such situations.

Medical treatment of stage I nasal polyposis over a 3-year follow-up period.

PURPOSE: To determine the effects of a standardized therapeutic protocol (short-term oral administration of prednisolone and daily intranasal spray of beclometasone) on stage I nasal polyposis over a follow-up period of 3 years. PROCEDURES: Assessments (evaluation of nasal function and drug consumption) were conducted at baseline and every 3 months on 54 consecutive patients with stage I nasal polyposis during 3 years. RESULTS: Over the follow-up period of 3 years, this dual modality proved to be successful in 87% of the subjects; only 13% had to undergo surgery after its failure. The average symptom reduction reached an improvement rate varying from 66 to 94.8%, according to the symptom type. The daily dosage of prednisolone and beclometasone was progressively decreased, while the gain in nasal comfort was being preserved. CONCLUSION: Management of stage I nasal polyps should be primarily medical.

Lymphocele after neck dissection.

The current report documents a case of lymphocele after neck dissection and reviews the management and treatment options.

Corticosteroid treatment in nasal polyposis with a three-year follow-up period.

OBJECTIVES/HYPOTHESIS: The management of nasal polyposis is undoubtedly a controversial subject. The part played by surgery seems to be steadily growing, if the number of published reports dedicated to this approach is any yardstick. Although the medical treatment remains the undisputed therapeutic mainstay, trials dedicated to the long-term assessment of its overall efficacy are scarce. STUDY DESIGN: Retrospective medical record review. METHODS: The aim of the study is focused on the evaluation of a dual modality, topical and systemic, over a follow-up period of 3 years. In all, 100 patients were treated according to a standardized therapeutic protocol combining short-term oral administration of prednisolone and daily intranasal spray of beclomethasone. RESULTS: Over the follow-up period of 3 years, this dual modality proved to be successful in 85% of the patients; only 15% had to undergo surgery after its failure. The average symptom reduction reached an improvement rate varying from 58% to 80%, according to the symptom type. The daily dosage of prednisolone and beclomethasone was progressively decreased while the gain in nasal comfort was being preserved. CONCLUSIONS: Management of nasal polyps should be primarily medical. Resorting to surgical procedures should not be envisaged before a trial is conducted of dual steroid therapy under a regimen of strict compliance to treatment.