Treatment of the neck in residual/recurrent disease after chemoradiotherapy for advanced primary laryngeal cancer.

Concomitant chemoradiotherapy (CRT) is extensively used as primary organ preservation treatment for selected advanced laryngeal squamous cell carcinomas (LSCC). The oncologic outcomes of such regimens are comparable to those of total laryngectomy followed by adjuvant radiotherapy. However, the management of loco-regional recurrences after CRT remains a challenge, with salvage total laryngectomy being the only curative option. Furthermore, the decision whether to perform an elective neck dissection (END) in patients with rN0 necks, and the extent of the neck dissection in patients with rN + necks is still, a matter of debate. For rN0 patients, meta-analyses have reported occult metastasis rates ranging from 0 to 31 %, but no survival advantage for END. In addition, meta-analyses also showed a higher incidence of complications in patients who received an END. Therefore, END is not routinely recommended in addition to salvage laryngectomy. Although some evidence suggests a potential role of END for supraglottic and locally advanced cases, the decision to perform END should weigh benefits against potential complications. In rN + patients, several studies suggested that selective neck dissection (SND) is oncologically safe for patients with specific conditions: when lymph node metastases are not fixed and are absent at level IV or V. Super-selective neck dissection (SSND) may be an option when nodes are confined to one level. In conclusion, current evidence suggests that in rN0 necks routine END is not necessary and that in rN + necks with limited nodal recurrences SND or a SSND could be sufficient.

Adjuvant chemotherapy is associated with better oncological outcomes after ALPPS for colorectal liver metastases.

ALPPS enables complete tumor resection in a shorter interval and a larger number of patients than classic two-stage hepatectomies. However, there is little evidence regarding long-term outcomes in patients with colorectal liver metastases (CLM). This study aims to evaluate the short and long-term outcomes of ALPPS in patients with CRM. Single-cohort, prospective, observational study. Patients with unresectable CLM due to insufficient liver remnant who underwent ALPPS between June 2011 and June 2021 were included. Of 32 patients treated, 21 were male (66%) and the median age was 56 years (range = 29-81). Both stages were completed in 30 patients (93.7%), with an R0 rate of 75% (24/32). Major morbidity was 37.5% and the mortality nil. Median overall survival (OS) and recurrence-free survival (RFS) were 28.1 and 8.8 months, respectively. The 1-3, and 5-year OS was 86%, 45%, and 21%, and RFS was 42%, 14%, and 14%, respectively. The only independent risk factor associated with poor RFS (5.7 vs 11.6 months; p = 0.038) and OS (15 vs 37 months; p = 0.009) was not receiving adjuvant chemotherapy. KRAS mutation was associated with worse OS from disease diagnosis (24.3 vs. 38.9 months; p = 0.025). ALPPS is associated with favorable oncological outcomes, comparable to traditional strategies to increase resectability in patients with CLM and high tumor burden. Our results suggest for the first time that adjuvant chemotherapy is independently associated with better short- and long-term outcomes after ALPPS. Selection of patients with KRAS mutations should be performed with caution, as this could affect oncological outcomes.

Agenesis of the gallbladder: A multicenter case series and review of the bibliography. / Agenesia de la vesícula biliar: una serie de casos multicéntrica y revisión de la literatura.

Gallbladder agenesis is a rare condition in pediatrics that is usually asymptomatic and represents a diagnostic challenge for physicians seeing these cases for the first time. Some patients may, however, present with symptoms that mimic other diseases of the bile ducts, and many of them undergo surgery due to such suspicion. Still, a timely diagnosis of gallbladder agenesis allows for medical treatment that is often sufficient to resolve the patient's problem. Although it is a benign condition, patients often present with other associated, more serious malformations and should be actively studied for a timely referral to other specialists. Here we describe our experience with the diagnosis and treatment of these patients and a brief review of the bibliography. We hope it will be helpful for physicians facing similar cases.

La agenesia de la vesícula biliar es una entidad rara en pediatría con una evolución normalmente silente, y representa un desafío diagnóstico para el médico que enfrenta estos casos por primera vez. Algunos pacientes pueden, sin embargo, presentar síntomas que simulan otras patologías del árbol biliar, y muchos de ellos son operados ante esta sospecha. Sin embargo, el diagnóstico oportuno de esta entidad permite llevar a cabo un tratamiento médico que muchas veces es suficiente para resolver el problema del paciente. Si bien es una condición benigna, los pacientes suelen presentar otras malformaciones asociadas que son más graves en naturaleza y que deben investigarse activamente para poder derivarlos a los especialistas de manera oportuna. Presentamos nuestra experiencia en el diagnóstico y tratamiento de estos pacientes, así como una breve revisión de la literatura. Esperamos que sea de utilidad para el médico que encuentre un caso similar.

Peer review of the pesticide risk assessment of the active substance clove oil.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, Malta, for the pesticide active substance clove oil are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions for the amendment of approval were reached on the basis of the evaluation of the representative use of clove oil as a preharvest nematicide on tomatoes and cucumbers (permanent greenhouse use). The representative use evaluated for the renewal of approval of clove oil was as post-harvest fungicide and bactericide on apples, pears and peaches (indoor uses). The reliable endpoints appropriate for use in regulatory risk assessment are presented. Endpoints not relevant to the scope of the proposed amendment of approval conditions will be addressed in the context of the renewal of approval procedure of clove oil running in parallel (AIR IV, EFSA Q-2016-00809). Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Initial surgical management of sporadic medullary thyroid cancer: Guidelines based optimal care - A systematic review.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the surgical management of sporadic MTC (sMTC), optimal initial surgical management of the thyroid, the central and the lateral neck remains a matter of debate. METHODS: A systematic review in PubMed and Scopus for current guidelines addressing the surgical management of sMTC and its referenced citations was conducted as per the PRISMA guidelines. RESULTS: Two-hundred and one articles were identified, of which 7 met the inclusion criteria. Overall, guidelines vary significantly in their recommendations for the surgical management of sMTC. Only one guideline recommended partial thyroidectomy for limited disease, but the possibility to avoid completion thyroidectomy in selected cases is acknowledged in 42% (3/7) of the remaining guidelines. The majority of guidelines (71.4%; 5/7) recommended prophylactic central neck dissection (CND) for all patients while the remaining two guidelines recommended CND based on Ct level and tumor size. The role of prophylactic lateral neck dissection based on preoperative Ct levels was recommended by 42% (3/7) of guidelines. Overall, these guidelines are based on low-quality evidence, mostly single-center retrospective series, some of which are over 20 years old. CONCLUSION: Current surgical management guidelines of sMTC should be revised, and ought to be based on updated data challenging current recommendations, which are based on historic, low-quality evidence. Partial thyroidectomy may become a viable option for small, limited tumors. Prospective, multi-center studies may be useful to conclude whether prophylactic ND is necessary in all sMTC patients.

Effects of polyphenol supplementation on hepatic steatosis, intima-media thickness and non-invasive vascular elastography in obese adolescents: a pilot study protocol.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible. METHODS AND ANALYSIS: This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12-18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study's feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome. ETHICS AND DISSEMINATION: This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals. CLINICALTRIALS: gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023. TRIAL REGISTRATION NUMBER: NCT03994029.

Pediatric living donor liver transplant for Budd-Chiari syndrome using a cryopreserved pulmonary vein graft for retro-hepatic vena cava reconstruction: A case report.

INTRODUCTION: In pediatric patients with Budd-Chiari syndrome (BCS), living donor liver transplantation (LDLT) raises substantial challenges regarding IVC reconstruction. CASE PRESENTATION: We present a case of an 8-year-old girl with BCS caused by myeloproliferative syndrome with JAK2 V617F mutation. She had a complete thrombosis of the inferior vena cava (IVC) with multiple collaterals, developing a Budd-Chiari syndrome. She underwent LDLT with IVC reconstruction with a cryopreserved pulmonary vein graft obtained from a provincial biobank. The living donor underwent a laparoscopic-assisted left lateral hepatectomy. The reconstruction of the vena cava took place on the back table and the liver was implanted en bloc with the reconstructed IVC in the recipient. Anticoagulation was immediately restarted after the surgery because of her pro-thrombotic state. Her postoperative course was complicated by a biliary anastomotic leak and an infected biloma. The patient recovered progressively and remained well on outpatient clinic follow-up 32 weeks after the procedure. CONCLUSION: IVC reconstruction using a cryopreserved pulmonary vein graft is a valid option during LDLT for pediatric patients with BCS where reconstruction of the IVC entails considerable challenges. Early referral to a pediatric liver transplant facility with a multidisciplinary team is also important in the management of pediatric patients with BCS.

Adenomyomatosis of the Gallbladder as a Cause of Abdominal Pain in Pediatrics: A Case Report of an Adolescent and a Literature Review.

Objectives: Adenomyomatosis (ADM) of the gallbladder is a benign condition, which is characterized by mucosal hyperplasia of the gallbladder and formation of intramucosal invagination through the thickened mucosal layer. The pathogenesis is unclear. This condition is rare in children. The aim of this publication is to present the case of a teenager with ADM of the gallbladder and review the pediatric literature on this topic. Methods: A 17-year-old female presented with severe postprandial right upper quadrant abdominal pains. The abdominal ultrasound revealed ADM of the gallbladder. Results: A curative laparoscopic cholecystectomy was performed. Since 1998, eleven of the 13 pediatrics cases reported with ADM of the gallbladder were symptomatic and a cholecystectomy was curative in all of them. Conclusion: ADM of the gallbladder should be considered in the differential diagnosis of recurrent right abdominal upper quadrant pains in pediatrics. Abdominal ultrasound is the best diagnostic procedure. In symptomatic patients, a cholecystectomy is curative.

BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine.

Recent publications have explored intranasal (i.n.) adenovirus-based (Ad) vaccines as an effective strategy for SARS-CoV-2 in pre-clinical models. However, the effects of prior immunizations and infections have yet to be considered. Here, we investigate the immunomodulatory effects of Mycobacterium bovis BCG pre-immunization followed by vaccination with an S-protein-expressing i.n. Ad, termed Ad(Spike). While i.n. Ad(Spike) retains some protective effect after 6 months, a single administration of BCG-Danish prior to Ad(Spike) potentiates its ability to control viral replication of the B.1.351 SARS-CoV-2 variant within the respiratory tract. Though BCG-Danish did not affect Ad(Spike)-generated humoral immunity, it promoted the generation of cytotoxic/Th1 responses over suppressive FoxP3+ TREG cells in the lungs of infected mice. Thus, this vaccination strategy may prove useful in limiting future pandemics by potentiating the long-term efficacy of mucosal vaccines within the context of the widely distributed BCG vaccine.

Enfermedad hepática en la fibrosis quística pediátrica. Una revisión de los conocimientos actuales / Cystic fibrosis liver disease in children ­ A review of our current understanding

La fibrosis quística, la segunda enfermedad genética más frecuente, es el resultado de una proteína de canal mutada, la CFTR, que secreta iones de cloro que fluidifican las secreciones. La esperanza de vida en los pacientes ha aumentado en años recientes gracias a mejoras en el tratamiento. No obstante, las complicaciones hepáticas son la tercera causa de muerte y la comprensión de su fisiopatología es aún deficiente. Se considera que la obstrucción biliar secundaria a la presencia de secreciones espesas conduce a la cirrosis. Sin embargo, el ácido ursodesoxicólico no ha modificado la historia natural. Además, la presencia de hipertensión portal en ausencia de cirrosis no puede ser explicada. Se ha propuesto el rol de la CFTR como modulador de tolerancia inmune, que explica la presencia de una inflamación portal persistente que culmina en fibrosis. El eje intestino-hígado tendría un rol importante en la presentación y la progresión de esta enfermedad

Cystic fibrosis is the second most common genetic disease in infancy. It is the result of a mutated channel protein, the CFTR, which secretes chloride ions, fluidifying secretions. Recent improvements in the treatment have increased life expectancy in these patients. Nevertheless, liver involvement remains the third cause of death. Unfortunately, our understating of the physiopathology is still deficient. Biliary obstruction secondary to the presence of thick secretions is considered to lead to cirrhosis. However, treatment with ursodeoxycolic acid has not changed the natural history. Furthermore, the presence of portal hypertension in the absence of cirrhosis cannot be explained. Recently, the role of CFTR as modulator of immune tolerance has been proposed, which could explain the presence of a persistent portal inflammation leading to fibrosis, and the gut-liver axis would also have a role in disease presentation and progression.

Sífilis congénita e infarto hepático, una asociación no reportada. Descripción de un caso pediátrico / Congenital syphilis and hepatic infarction, a not previously reported association. A pediatric case report

La sífilis congénita es causada por la infección del feto con Treponema pallidum durante el embarazo. Los síntomas son variables. Si bien es común el daño endotelial, no suele estar presente en los casos congénitos. Reportamos el caso de un lactante de 42 días de vida hospitalizado por masa abdominal. Las imágenes confirmaban la presencia de una lesión en el lóbulo hepático izquierdo sin efecto de masa. Las biopsias mostraron cambios compatibles con infarto y hepatitis neonatal. Las serologías del paciente y de su madre confirmaron el diagnóstico de sífilis congénita, y recibió tratamiento con penicilina intravenosa. El hígado se encuentra protegido de los daños isquémicos gracias a su doble irrigación, pero la acumulación de noxas puede haber provocado dicha presentación inusual. Tres meses más tarde, el paciente se encontraba libre de síntomas y la resonancia de control mostró atrofia del lóbulo izquierdo, mientras el resto del parénquima no presentaba alteraciones.

Congenital syphilis is caused by Treponema pallidum infection of the fetus during pregnancy. Symptoms are variable. While endothelial damage is common, it is not usually present in congenital cases. Here we report the case of a 42-day-old infant hospitalized due to an abdominal mass. Imaging studies confirmed the presence of an injury in the left lobe of the liver without mass effect. Biopsies showed changes compatible with infarction and neonatal hepatitis. The patient's and his mother's serologies confirmed the diagnosis of congenital syphilis, and he was treated with intravenous penicillin. The liver protected from ischemic injury by its double irrigation, but the accumulation of harmful agents may have caused this unusual presentation. Three months later, the patient was symptom-free, and the control MRI showed atrophy of the left lobe, while the rest of the parenchyma was unchanged.

EFAS Score-Validation of Spanish and Estonian Versions by the Score Committee of the European Foot and Ankle Society (EFAS).

BACKGROUND: The Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in 11 languages (Dutch, English, German, Finnish, French, Italian, Polish, Portuguese, Persian, Swedish, Turkish). From other languages under validation, the Spanish and Estonian versions completed data acquisition and underwent further validation. METHODS: The EFAS Score was developed and validated in three stages: 1) item (question) identification (completed during the initial validation study), 2) item reduction and scale exploration (completed during the initial validation study), 3) confirmatory analyses and responsiveness of the Spanish and Estonian versions (completed during the initial validation study in seven other languages). The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory. RESULTS: The internal consistency of the scale was confirmed in the Spanish and Estonian versions (Cronbach's Alpha>0.8). Responsiveness was good, with moderate to large effect sizes in both languages, and evidence of a statistically significant positive association between the EFAS Score and patient-reported improvement. CONCLUSIONS: The Spanish and Estonian EFAS Score versions were successfully validated in orthopaedic ankle and foot surgery patients, with a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.net.

Cystic fibrosis liver disease in children - A review of our current understanding. / Enfermedad hepática en la fibrosis quística pediátrica. Una revisión de los conocimientos actuales.

Cystic fibrosis is the second most common genetic disease in infancy. It is the result of a mutated channel protein, the CFTR, which secretes chloride ions, fluidifying secretions. Recent improvements in the treatment have increased life expectancy in these patients. Nevertheless, liver involvement remains the third cause of death. Unfortunately, our understating of the physiopathology is still deficient. Biliary obstruction secondary to the presence of thick secretions is considered to lead to cirrhosis. However, treatment with ursodeoxycolic acid has not changed the natural history. Furthermore, the presence of portal hypertension in the absence of cirrhosis cannot be explained. Recently, the role of CFTR as modulator of immune tolerance has been proposed, which could explain the presence of a persistent portal inflammation leading to fibrosis, and the gut-liver axis would also have a role in disease presentation and progression.

La fibrosis quística, la segunda enfermedad genética más frecuente, es el resultado de una proteína de canal mutada, la CFTR, que secreta iones de cloro que fluidifican las secreciones. La esperanza de vida en los pacientes ha aumentado en años recientes gracias a mejoras en el tratamiento. No obstante, las complicaciones hepáticas son la tercera causa de muerte y la comprensión de su fisiopatología es aún deficiente. Se considera que la obstrucción biliar secundaria a la presencia de secreciones espesas conduce a la cirrosis. Sin embargo, el ácido ursodesoxicólico no ha modificado la historia natural. Además, la presencia de hipertensión portal en ausencia de cirrosis no puede ser explicada. Se ha propuesto el rol de la CFTR como modulador de tolerancia inmune, que explica la presencia de una inflamación portal persistente que culmina en fibrosis. El eje intestino-hígado tendría un rol importante en la presentación y la progresión de esta enfermedad.

Equidad de género y motivación en educación física. ¿podría ayudarnos la híbridación de modelos pedagógicos? / Equidade de gênero e motivação em educação física. poderia ajudar-nos a hibridação de modelos pedagógicos? / Motivation and gender equity in physical education. could hybridization of pedagogical models help us?

Resumen El presente estudio valoró la influencia de una unidad híbrida sobre la motivación, la satisfacción de las NPB, la intención de ser físicamente activo y la satisfacción hacia la clase de EF. El género fue considerado como variable de interés. Se hibridaron los modelos Educación Deportiva (MED) y Teaching Games for Understanding (TGfU) en una unidad de minibalonmano para cuatro grupos de Educación Secundaria, de entre 13 y 15 años (n=70). En otras tres clases (grupo control, n=67) se planteó un enfoque tradicional. Se planteó un análisis inferencial MANOVA inter e intragrupo, pre y post test. El grupo experimental mostró mejoras significativas para casi todas las variables. Las diferencias de género previas se minimizaron o eliminaron en todas las variables. Ambos géneros parecen tener valores similares de motivación más autodeterminada, mejorando su satisfacción hacia las clases de EF y la intención de ser físicamente activos, favoreciendo un entorno más equitativo.

Resumo O presente estudo valorizou a influência em uma unidade híbrida sobre a motivação, satisfação das NPB, intenção de ser fisicamente ativo e a satisfação em relação à aula de EF. Considerou-se o gênero como variável de interesse. Recorrendo à hibridação dos modelos Educação Desportiva (MED) e Teaching Games for Understanding (TGfU) em uma unidade de mini-handebol dirigida a quatro turmas do Ensino Fundamental, entre 13 e 15 anos (n=70). Noutras três aulas (grupo de controlo, n=67) propôs uma abordagem tradicional. Propôs uma análise dedutiva MANOVA inter e intragrupal pré e pós-teste. A turma experimental melhorou significativamente em quase todas as variáveis. As diferenças de gênero prévias minimizaram ou foram eliminadas no que respeita a todas as variáveis. Além disso, os meninos e as meninas parecem ter valores semelhantes de motivação mais autodeterminada, melhorando a satisfação em relação à classe de educação física e a intenção de ser fisicamente ativo.

Abstract The present study analyzed the influence of a hybrid unit on Motivation, BPN satisfaction, Intention to be Physically Active and Satisfaction in PE class. Gender was considered as a variable of interest. Sport Education Model (SE) and Teaching Games for Understanding (TGfU) were hybridized in a mini handball unit for four secondary education groups, aged between 13 and 15 years (n=70). In other three classes (n=67) a traditional approach was proposed, working as a control group. Pre and post test MANOVA inferential analysis was conducted between and within groups. Experimental group showed significative results in almost all variables. Preliminary gender differences were removed or minimized for all variables. The hybridization of pedagogical models could support a more inclusive, equitable environment. Both genders showed similar values of self-determined motivation and improved both their satisfaction in PE classes and their intention to be physically active.

Peer review of the pesticide risk assessment of the active substance rape seed oil.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the Netherlands and co-rapporteur Member State Finland for the pesticide active substance rape seed oil and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative professional and non-professional uses of rape seed oil as an acaricide on pome fruit trees (field use), berries, vegetables, ornamentals (greenhouse and field uses) and as an insecticide on potatoes (field use). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed.

Peer review of the pesticide risk assessment of the active substance oxamyl.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Italy, and co-rapporteur Member State, France, for the pesticide active substance oxamyl and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of oxamyl as a nematicide on potato and tobacco (field use), on tomato (permanent greenhouse), on cucurbits (edible and inedible peel), pepper, aubergine and plants nurseries of the above-mentioned crops on soil bed preparation (permanent greenhouse). The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Buske-Lowenstein Tumor: A Rare Cause of Genital Warts.

The Buschke-Löwenstein tumor (BLT), also known as giant condylomata acuminata (GCA), is a pseudo-epithelial proliferation engendered by the human papillomavirus (HPV). Interestingly, its location at the anal margin, or perianal skin, is rare. The authors present the case of a gentleman who became unstable while standing, stating that his ears were ringing. His emergency presentation, clinical course, and imaging findings are discussed. The patient presented with signs of condyloma acuminata and BLT. This can be excised through surgery and removed with the help of adjuvant treatments, but there is still much to learn about this disease.

Clinical and genetic features of a large homogeneous cohort of oculopharyngeal muscular dystrophy patients from the Canary Islands.

BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset myopathy characterized by ptosis, dysphagia, and progressive proximal limb muscle weakness. The disease is produced by a short expansion of the (GCN)n triplet in the PABPN1 gene. The size of expansion has been correlated to the disease onset and severity. We report the clinical features of a large cohort of OPMD patients harboring the (GCN)15 allele from the Canary Islands. METHODS: A retrospective observational study was performed analyzing the clinical, demographic, and genetic data of 123 OPMD patients. Clinical data from this cohort were compared with clinical data collected in a large European study including 139 OPMD patients. RESULTS: A total of 113 patients (94.2%) carried the (GCN)15 expanded PABN1 allele. Age of symptoms' onset was 45.1 years. The most frequent symptom at onset was ptosis (85.2%) followed by dysphagia (12%). The severity of the disease was milder in the Canary cohort compared to European patients as limb weakness (35.1% vs. 50.4%), the proportion of patients that require assistance for walking or use a wheelchair (9.3% vs. 27.4%), and needed of surgery because of severe dysphagia (4.6% vs. 22.8%) was higher in the European cohort. CONCLUSIONS: Nearly 95% of patients with OPMD from the Canary Islands harbored the (GCN)15 expanded allele supporting a potential founder effect. Disease progression seemed to be milder in the (GCN)15 OPMD Canary cohort than in other cohorts with shorter expansions suggesting that other factors, apart from the expansion size, could be involved in the progression of the disease.

Peer review of the pesticide risk assessment of the active substance fish oil.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the Czech Republic and co-rapporteur Member State France for the pesticide active substance fish oil and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of fish oil as a game repellent on deciduous and coniferous trees in forestry. The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed.