Real-world EGFR testing practices for non-small-cell lung cancer by thoracic pathology laboratories across Europe.

BACKGROUND: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). MATERIALS AND METHODS: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021. RESULTS: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. CONCLUSIONS: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.

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.

Sulfasalazine: A rare cause of acute eosinophilic pneumonia.

Sulfasalazine is a compound of 5-aminosalicylic acid (5-ASA) and sulfapyridine joined by an azo bond. It is a widely used drug in the treatment of chronic inflammatory bowel disease. Fatal toxicity of sulfasalazine arises from its effects on the bone marrow and the resulting blood dyscrasias. Pulmonary toxicity from sulfasalazine is a rather rare finding. Here, we present the case of a patient who developed acute eosinophilic pneumonia with sulfasalazine use.

Familial hematological malignancies: ASXL1 gene investigation.

PURPOSE: Familial aggregation among patients with several hematological malignancies has been revealed. This emphasizes the importance of genetic factors. Only few genes predisposing to familial hematological malignancies have been reported until now due to the low occurrence. We have described in previous study PRF1 and CEBPA variants that might contribute to the background of genetic factors, which encourage us to extend our investigations to other cooperating genes. The aim of this study is to determine whether germline additional sex combs-like 1 (ASXL1) gene mutations may be involved? METHODS/PATIENTS: In this study, we investigated the candidate gene ASXL1 by direct sequencing in 88 unrelated Tunisian and French families with aggregated hematological malignancies. RESULTS: We report a new p.Arg402Gln germline missense substitution in two related Tunisian patients which has not been previously described. We identified here this variant for the first time in non-Hodgkin lymphoma. The p.Arg402Gln variant was not found in 200 control chromosomes. In silico analysis has predicted potential deleterious effect on ASXL1 protein. CONCLUSIONS: From an extended candidate genes analyzed in the field of familial hematological malignancies, ASXL1 might be involved. This variant should be considered since a potential damaging effect was predicted by in silico analysis, with a view to develop functional assay in order to investigate the biological assessment.

"Soccer or emergency?" sporting event can lead to a decreased attendance in the pediatric emergency department.

AIM: Sporting events have been seen to be related to a decline in adult male visits in emergency departments. Studies about the influence of sporting events on pediatric emergency attendance are scarce and non-conclusive. In our institution there is a widely shared popular belief of the local pediatric emergency medical staff that there is a decrease in the attendance when the local soccer team (Olympique de Marseille) is playing. METHODS: We have collected data on attendance and orientation (medical or surgery) in the pediatric emergency unit (35,000 annual admission) for the Wednesdays, Saturdays and Sundays between July 1, 2008 and May 31, 2012 compassing 4 soccer seasons. We have also collected the date and the localization (at home or abroad) of all the games played by the city's soccer team for the four seasons. RESULTS: The study included 512 days (171 Saturdays and Sundays and 170 Wednesdays), 173 were match days and 339 were control days. After adjusting for day, month, and years, there was a 3.5% decrease of attendance during game days (P=0.007), which was higher for days of away games (4.7% decrease, P=0.012). For matches played at 9 p.m. for a 4 hour period (allowing for 1 hour before and 1 hour after the matches) the decrease was that of 8% (P=0.05) mostly for medicine admission. CONCLUSION: We observed that sporting events as soccer games can have a effect on the attendance rate in a children's emergency department. The underlying reason for this difference is not well understood.

Atypical melanocytic naevi following melanotan injection.

Melanotan is a synthetic analogue of alpha melanocyte stimulating hormone (a-MSH) that stimulates melanogenesis. It is sold on the internet and tanning salons as a quick 'tanning jab'. We report a patient who developed multiple new onset atypical naevi within one week of receiving two Melanotan injections. This case highlights the potential risk of Melanotan in stimulating dysplastic naevi or possibly malignant melanoma.

[Samuel Pozzi (1846-1918), flamboyant surgeon of la Belle Epoque]. / Samuel Pozzi (1846-1918), chirurgien flamboyant de la Belle Epoque.

Samuel Pozzi was an outstanding in the Paris of nineteenth century, highly gifted and successful, but his real personality remains, after one hundred years, filled with mystery. He was born in the heart of Dordogne, Bergerac, in a family of Huguenots who had come from Geneva. After his first studies in Pau and Bordeaux, he came to Paris, while barely eighteen years old to reach the heights of the medical world of his time. Beginning as "Interne" then "Chirurgien des hôpitaux", "professeur agrégé", head Physician at Hôpital Broca and, finally he was appointed Professor to the newly created Chair of Clinical Gynecology. He gained fame as a master of gynecological surgery but kept, during his career, a keen interest for all fields of surgery, including organ transplantation.

Component-resolved diagnosis with commercially available D. pteronyssinus Der p 1, Der p 2 and Der p 10: relevant markers for house dust mite allergy.

OBJECTIVE: To establish the prevalence and serum levels of IgE to commercial Der p 1, Der p 2, Der p 10 and the carbohydrate MUXF3 in house dust-mite allergic patients. To compare individual vs. allergen microarray methods. METHODS: Prevalence and serum levels of IgE to Dermatophagoides pteronyssinus extract and components Der p 1, Der p 2, Der p 10 and MUXF3, specific IgG4 to D. pteronyssinus, total serum IgE levels, and clinical features (age, asthma, rhinitis and atopic dermatitis) were determined in 123 patients (64 children) with the ImmunoCAP® method. ImmunoCAP ISAC® was performed in 24 patients. RESULTS: All patients had serum IgE to D. pteronyssinus. Prevalences of serum IgE to commercial components were Der p 1 93%, Der p 2 77% (Der p 1 or Der p 2 94%), Der p 10 28% and MUXF3 25%. Levels of D. pteronyssinus IgE strongly correlated with Der p 1 and Der p 2 IgE (r = 0.89 and 0.85 respectively), but not Der p 10 and MUXF3. ImmunoCAP® and ImmunoCAP ISAC® were concordant, but the quantitative correlation was poor. No clinical implication for the prevalence, levels, or molecular IgE reactivity profile to house dust mite components was found. CONCLUSIONS AND CLINICAL RELEVANCE: Commercially available Der p 1 and Der p 2 strongly correlate with IgE D. pteronyssinus. The lack of Der p 1 and Der p 2 IgE may help with differential diagnosis. Der p 10 serum IgE prevalence and levels suggest different patterns in food and mite-related tropomyosin sensitization. Serum IgE to carbohydrate MUXF3, although unexpectedly prevalent, were low and did not modify D. pteronyssinus IgE levels. Follow-up may be best carried out with individual rather than microarrayed components.

Inter-tibiofibular graft for traumatic segmental bone defect of the tibia.

INTRODUCTION: The present study sought to assess the interest of inter-tibiofibular graft (ITFG), alternatively called posterolateral bone graft, in traumatic segmental tibial bone defect. MATERIAL AND METHODS: Twenty-eight ITFGs were performed in 125 tibial reconstructions for traumatic bone defect. Patient's records were reviewed retrospectively in a multicenter study. Tibial reconstruction with and without ITFG was compared for bone healing and patient's return to full weight-bearing status. RESULTS: There were no failures of bone healing in the ITFG group, versus 14 (14%) in the non-ITFG group. Graft-to-consolidation delays were shorter with first-line ITFG, at a mean 10 months (range, 3-20 months) versus 16.5 months (range, 3-63 months) in the non-ITFG group (P<0.05). Weight-bearing was likewise more quickly resumed, with full weight-bearing at a mean 9 months (range, 3-19 months) versus 15 months (range, 1-34 moths) respectively (P<0.05). Return to work was also quicker, at a mean 15 months (range, 4-28 months) versus 27 months (range, 8-56 months) respectively (P<0.05). DISCUSSION: This study confirmed the interest of ITFG in tibial bone defect reconstruction. ITFG may singly be used for small defects less than 4 cm, or in conjunction with another tibial reconstruction technique; ITFG in the present series achieved consolidation in all cases and significantly shortened the times to return to full weight-bearing status and to work. LEVEL OF EVIDENCE: III: retrospective case-control study.

Proximal end clavicle fracture from a parachute jumping injury.

Fractures of the medial end of the clavicle are the least common type of clavicle fracture. We report a 29-year-old military parachutist who presented with medial end clavicle fracture after a bad landing. He was first treated non-operatively in a tertiary center and was then referred to our center by his general practitioner. Surgery was indicated since the fracture was displaced and the patient needed anatomical reconstruction to promote rapid bone healing and a prompt return to work. The medial fragment being comminuted, K-wires were used for internal fixation instead of a plate. The two K-wires were bent 180° to avoid risk of migration and were removed 3 months after surgery when the patient had begun to perform all activities without pain. Aggressive treatment is recommended for medial end clavicle fracture in case of displacement and facilitates rapid functional recovery, notably in patients with considerable clavicular demand.

Hip circumference is associated with the risk of premenopausal ER-/PR- breast cancer.

OBJECTIVE: We evaluated the relationship between hip and waist circumferences (HCs, WCs), waist-to-hip ratio, height, weight and body mass index (BMI) and breast cancer risk according to menopausal status of women and cancer hormone receptor status. DESIGN: We used data from the French E3N longitudinal prospective cohort. SUBJECTS: In the total population of 63 726 women who were analyzed, 1887 breast cancer cases were diagnosed during follow-up. RESULTS: Among postmenopausal women, the risk of ER+/PR+ breast cancer increased with increasing weight, BMI, and both HCs and WCs, although these two associations disappeared after adjustment for BMI. No association was seen with ER-/PR- breast cancers. Among premenopausal women, among the different factors studied, HC only (no association was observed for any of the different factors studied except for HC) was associated with an increased risk of ER+/PR+ breast cancer after adjustment for BMI (hazard ratio (HR)=1.65; (1.04-2.62) when comparing the highest to lowest tertile; P-trend across tertiles=0.03) and of ER-/PR- breast cancer both before and after adjustment for BMI (HR=2.85 (1.33-6.13); P-trend <0.01, and HR=3.13 (1.19-8.27) P-trend =0.02, respectively). In the latter group, the association with HC was observed whatever the WC (HR=2.81 (1.18-6.70) and HR=2.79 (1.16-6.76) in women with high HC/low WC and high HC/high WC, respectively). CONCLUSION: The increase in risk of premenopausal breast cancer associated with large HC for both ER+/PR+ and ER-/PR- subtypes may provide insight into a specific risk factor for premenopausal breast cancer.

Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene: epidemiological study and lessons from eight years of genetic analysis in France.

BACKGROUND: Cryopyrin-associated periodic syndromes (CAPS) consist of a continuum of autoinflammatory diseases caused by a defect in interleukin 1ß regulation. Although symptoms may vary widely, the discovery, in 2001, of the gene involved (NLRP3) has dramatically helped diagnosis. OBJECTIVES: To define the spectrum and prevalence of NLRP3 mutations in France and to delineate initial criteria before molecular analysis. METHODS: Retrospective review (2001-9) of genetic analysis data and request forms of patients living in France with an NLRP3 mutation since the set up of CAPS molecular diagnosis by the three French laboratories providing this test (GenMAI network). RESULTS: Over 800 analyses of this gene have been conducted, identifying 135 cases with an NLRP3 mutation (55 probands; 33 multiplex families); the estimated prevalence in France was equal to 1/360 000. A total of 21 different sequence variants were detected, among which four are common and nine are new mutations. CONCLUSIONS: Although the number of NLRP3 test requests has doubled over the past 5 years, genetic screening has not contributed to enhanced detection of new index cases each year. There are two possible reasons for this: (i) no clinical prerequisite for genetic diagnosis and (ii) few new large families are now identified (unlike the initial study based on a selection by linkage). A set of initial clinical criteria have been drawn up which it is recommended should be fulfilled before a patient is tested: at least three recurrent bouts, age at disease onset < 20 years and elevated levels of C-reactive protein, especially in individuals with urticaria and moderate fever.