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Glioblastoma (GBM) is an obligatory lethal brain tumor with a median survival, even with the best standard of care therapy, of less than 20 months. In light of this fact, the evaluation of new GBM treatment approaches such as oncolytic virotherapy (OVT) is urgently needed. Based on our preliminary preclinical data, the YB-1 dependent oncolytic adenovirus (OAV) XVir-N-31 represents a promising therapeutic agent to treat, in particular, therapy resistant GBM. Preclinical studies have shown that XVir-N-31 prolonged the survival of GBM bearing mice. Now using an immunohumanized mouse model, we examined the immunostimulatory effects of XVir-N-31 in comparison to the wildtype adenovirus (Ad-WT). Additionally, we combined OVT with the inhibition of immune checkpoint proteins by using XVir-N-31 in combination with nivolumab, or by using a derivate of XVir-N-31 that expresses a PD-L1 neutralizing antibody. Although in vitro cell killing was higher for Ad-WT, XVir-N-31 induced a much stronger immunogenic cell death that was further elevated by blocking PD-1 or PD-L1. In vivo, an intratumoral injection of XVir-N-31 increased tumor infiltrating lymphocytes (TILs) and NK cells significantly more than Ad-WT not only in the virus-injected tumors, but also in the untreated tumors growing in the contralateral hemisphere. This suggests that for an effective treatment of GBM, immune activating properties by OAVs seem to be of greater importance than their oncolytic capacity. Furthermore, the addition of immune checkpoint inhibition (ICI) to OVT further induced lymphocyte infiltration. Consequently, a significant reduction in contralateral non-virus-injected tumors was only visible if OVT was combined with ICI. This strongly indicates that for an effective eradication of GBM cells that cannot be directly targeted by an intratumoral OV injection, additional ICI therapy is required.

Glioblastoma (GBM) is an obligatory lethal brain tumor with a median survival, even with the best standard of care therapy, of less than 20 months. In light of this fact, the evaluation of new GBM treatment approaches such as oncolytic virotherapy (OVT) is urgently needed. Based on our preliminary preclinical data, the YB-1 dependent oncolytic adenovirus (OAV) XVir-N-31 represents a promising therapeutic agent to treat, in particular, therapy resistant GBM. Preclinical studies have shown that XVir-N-31 prolonged the survival of GBM bearing mice. Now using an immunohumanized mouse model, we examined the immunostimulatory effects of XVir-N-31 in comparison to the wildtype adenovirus (Ad-WT). Additionally, we combined OVT with the inhibition of immune checkpoint proteins by using XVir-N-31 in combination with nivolumab, or by using a derivate of XVir-N-31 that expresses a PD-L1 neutralizing antibody. Although in vitro cell killing was higher for Ad-WT, XVir-N-31 induced a much stronger immunogenic cell death that was further elevated by blocking PD-1 or PD-L1. In vivo, an intratumoral injection of XVir-N-31 increased tumor infiltrating lymphocytes (TILs) and NK cells significantly more than Ad-WT not only in the virus-injected tumors, but also in the untreated tumors growing in the contralateral hemisphere. This suggests that for an effective treatment of GBM, immune activating properties by OAVs seem to be of greater importance than their oncolytic capacity. Furthermore, the addition of immune checkpoint inhibition (ICI) to OVT further induced lymphocyte infiltration. Consequently, a significant reduction in contralateral non-virus-injected tumors was only visible if OVT was combined with ICI. This strongly indicates that for an effective eradication of GBM cells that cannot be directly targeted by an intratumoral OV injection, additional ICI therapy is required.

Background The ongoing supply-demand gap with respect to donor kidneys for transplantation necessitates the increased use of higher kidney donor profile index and/or donation after circulatory death (DCD) kidneys. Machine perfusion (MP) preservation has become increasingly popular as a means to preserve such organs. Human data regarding normothermic kidney MP (NMP) is in its infancy, and such a system has not been established in the Australasian clinical setting. Methods Modified cardio-pulmonary bypass technology was utilized to develop a viable NMP kidney perfusion system using a porcine DCD model. System development and optimization occurred in two stages, with system components added in each experiment to identify optimal perfusion conditions. Results Device functionality was demonstrated by the successful perfusion of and urine production by, eight porcine kidneys. Urine production diminished in the presence of colloid in the perfusate. Pressure-controlled (compared with flow-controlled) perfusion is preferable as a safe perfusion pressure range can be maintained. More physiologic perfusion conditions are achieved if oxygenation is provided by an oxygen/carbon dioxide mixture compared to 100% oxygen. Conclusion A viable and reproducible NMP system was established and tested in porcine kidneys, which was able to simulate graft function extra-corporeally. Further work is required to identify the most optimal perfusion conditions. Prior to its utilization in clinical transplantation, the system should be tested in non-transplanted human kidneys.

The prognosis for children diagnosed with high-risk acute lymphoblastic leukemia (ALL) remains sub-optimal, and more potent and less toxic treatments are urgently needed. We investigated the efficacy of a novel nicotinamide phosphoribosyltransferase inhibitor, OT-82, against a panel of patient-derived xenografts (PDXs) established from high-risk and poor outcome pediatric ALL cases. OT-82 was well-tolerated and demonstrated impressive single agent in vivo efficacy, achieving significant leukemia growth delay in 95% (20/21) and disease regression in 86% (18/21) of PDXs. In addition, OT-82 enhanced the efficacy of the established drugs cytarabine and dasatinib and, as a single agent, showed similar efficacy as an induction-type regimen combining three drugs used to treat pediatric ALL. OT-82 exerted its anti-leukemic action by depleting NAD(+) and ATP, inhibiting the NAD(+)-requiring DNA damage repair enzyme PARP-1, increasing mitochondrial ROS levels and inducing DNA damage, culminating in apoptosis induction. OT-82 sensitivity was associated with the occurrence of mutations in major DNA damage response genes, while OT-82 resistance was characterized by high expression levels of CD38. In conclusion, our study provides evidence that OT-82, as a single agent, and in combination with established drugs, is a promising new therapeutic strategy for a broad spectrum of high-risk pediatric ALL for which improved therapies are urgently needed.

Tuberculosis is a chronic granulomatous infection caused by Mycobacterium tuberculosis or bovis that can affect all organs. However being located in the salivary glands is rare, affecting mainly adults between 20 and 50 years, although a few cases were described in children. We reported a series of 4 children with parotid TB diagnosed and treated at the ENT department of the hospital of specialties of Rabat.The average age was 9.25 years and sex ratio M/F was 1. All children were admitted for parotid swelling evolving over an average period of 6 months which fistulized afterwards, a child had also facial paralysis. Histological analysis of the fine-needle aspiration or the sample taken from the fistula confirmed the diagnosis of tuberculosis with the presence of giant cell granuloma with caseous necrosis. All children received anti-bacillary treatment during 6 months, and showed good evolution.Although being rare, the parotid TB in children remains a condition to be considered at the occurrence of any chronic parotid swelling, especially in endemic countries.

Kikuchi-Fujimoto's disease KFD is a rare and benign cause of cervical lymphadenopathy. It is an anatomoclinical entity of unknown etiology. The confirmation of the diagnosis is always provided by histological lymph node study. The clinical picture sometimes evokes lymphoma or tuberculosis. The evolution is generally favorable with spontaneous healing after a few weeks. We report the case of a 26-year-old woman who had consulted for cervical lymphadenopathy associated with fever. The cervical lymph node biopsy concluded to Kikuch-Fujimoto's disease. The evolution was marked by rapid regression of lymphadenopathy under corticosteroid treatment.

Introduction: Infantile myofibromatosis (IM) is a rare benign mesenchymal tumor. It performs various clinical aspects. This is the most common fibromatosis of the child; it is characterized by a proliferation of fibroblasts and myofibroblasts with particular perivascular disposition. Methods: We report a case of a male child presented with a cervical mass since birth. Clinical examination showed a well circumscribed mass in the right cervical region. The Tomography objectified a benign look mass embedded in the sterno-mastoid and surgical resection was decided. Results: The mass was resected at the age of 2 years and 4 months. Pathological examination with immunohistochemical study allows to retain the diagnosis of infantile myofibromatosis. Conclusion: IM is a rare tumor that shows clinicopathological characteristics well defined. It should be considered as a differential diagnosis in any child with a solitary or multiple mesenchymal tumor, particularly that occurring during the first two years of life. Through this observation pathological, clinical, etiopathogenic and cytogenetic characteristics of this infantile tumor are described.

The ongoing supply-demand gap with respect to donor kidneys for transplantation necessitates the increased use of higher kidney donor profile index and/or donation after circulatory death (DCD) kidneys. Machine perfusion (MP) preservation has become increasingly popular as a means to preserve such organs. Human data regarding normothermic kidney MP (NMP) is in its infancy, and such a system has not been established in the Australasian clinical setting.Modified cardio-pulmonary bypass technology was utilized to develop a viable NMP kidney perfusion system using a porcine DCD model. System development and optimization occurred in two stages, with system components added in each experiment to identify optimal perfusion conditions.Device functionality was demonstrated by the successful perfusion of and urine production by, eight porcine kidneys. Urine production diminished in the presence of colloid in the perfusate. Pressure-controlled (compared with flow-controlled) perfusion is preferable as a safe perfusion pressure range can be maintained. More physiologic perfusion conditions are achieved if oxygenation is provided by an oxygen/carbon dioxide mixture compared to 100% oxygen.A viable and reproducible NMP system was established and tested in porcine kidneys, which was able to simulate graft function extra-corporeally. Further work is required to identify the most optimal perfusion conditions. Prior to its utilization in clinical transplantation, the system should be tested in non-transplanted human kidneys.

Summary: The purpose of this study is to reduce the search area of the marginal mandibular branch, this scarecrow nerve of the upper cervical surgery. Materials and methods: MMB dissection was applied to 25 anatomical subjects, who described an ABC Triangle where the MMB is still inside the cervical surgical position: A mandibular angle, B intersection of the MMB with the lower border of the mandible (LBM), C the position of the furthest MMB below the LBM. Results: This nerve is still depth of the superficial cervical fascia, and its division is constantly after the intersection with the facial vein (FV). The position of the MMB furthest from the LBM is found between 2 and 2.2 cm below the LBM and at 2/3 of the distance AX from the angle of the mandible angle to the intersection of the FV with the LBM. This distance AX represents the 2/3 of the distance AB from the angle of the mandible to the intersection of the MMB with the LBM and whose measurement is between 4 and 4.5 cm. Conclusion: This triangle ABC landmark of MMB provides reliable and constant anatomical markers allowing the surgeon locating or avoidance of MMB.

Kartagener syndrome is an autosomal recessive genetic ciliary disorder comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. It's the one of primary ciliary dyskinesia disorders with manifestations present from childhood. Most patients of PCD have situs inversus. We present a case of 18 year-old women with recurrent lower and upper respiratory tracts infections, and rhinolalia clausa.Pan African Medical Journal 2016; 23

Objectif : Les cellulites cervico-faciales diffuses restent des affections encore tres graves, seule une prise en charge precoce et multidisciplinaire permet d’esperer un bon pronostic. L’objectif de notre etude retrospective est d’etudier les differents aspects epidemiologiques, cliniques, paracliniques, therapeutiques, evolutifs et preventifs de ces pathologies, tout en comparant nos resultats aux donnees de la litterature. Patients et methodes : Notre etude porte sur 60 cas de cellulites cervico-faciales d’origine dentaire hospitalises dans le service d’ORL et de Chirurgie maxillofaciale de l’Hopital des Specialites de Rabat sur une periode de 4 ans, entre janvier 2005 et decembre 2008. Les facteurs favorisants ont ete etudie et analyse statistiquement par la methode analyse de la variance. Resultats : L’analyse de nos dossiers a trouve que cette pathologie touche les hommes plus que les femmes, avec une moyenne d’âge de 29 ans. Les facteurs favorisants ont ete etudie et analyse statistiquement par la methode analyse de la variance, qui a permis de les classer en trois niveaux selon leur importance : la prise d’anti-inflammatoires non steroidiens et la mauvaise hygiene bucco-dentaire en 1er niveau, ensuite le diabete en 2e niveau, et au 3e niveau l’extraction dentaire ainsi que la tentative d’extraction dentaire. Les dents les plus souvent en cause etaient des molaires mandibulaires avec un taux de 85,7 %. La prise en charge therapeutique a permis une evolution favorable dans 98,3 % des cas mais, dans un cas, l’evolution a ete marquee par la survenue de complications ayant entraine le deces. Conclusion : La precocite du diagnostic et de la prise en charge therapeutique doit etre pluridisciplinaire (medecine, chirurgie et parfois reanimation) pour permettre d’esperer une guerison sans complications ou sequelles. (Med Buccale Chir Buccale 2009 ; 15 : 127-135).

La macroglossie est un symptome qui peut etre associe a differentes affections; elle est souvent responsable de troubles fonctionnels (deglutition, respiration, phonation), d’intensite variable. Nous rapportons l’observation d’un enfant atteint d’un syndrome de Beckwith-Wiedemann et porteur d’une volumineuse macroglossie. La resection partielle de la langue a entraine une amelioration spectaculaire des troubles fonctionnels.

The metastasis of chromophobe renal cell carcinoma to head and neck region, described herein, has never been reported before to our knowledge. A 56-year-old woman with a history of nephrectomy, that revealed chromophobe renal cell carcinoma six years before, presented left cervical mass. Imaging showed with left cervical lymphadenopathies and thyroid nodule. Surgery with histopathological examination confirmed that it was a left central and lateral jugular lymph node metastasis of chromophobe renal cell carcinoma treated postoperatively by antiangiogenic therapy. The patient was successfully treated by surgery and antiangiogenic drugs with stabilization and no recurrence of the metastatic disease. The case and the literature reported here support that chromophobe renal cell carcinoma can metastasize to the head and neck region and should preferentially be treated with surgery and antiangiogenic therapy because of the associated morbidity and quality-of-life issues.

Primary hydatid cyst of thyroid gland is an exceptional localization even in Morocco where echinococcal disease is endemic. A 23-year-old woman presented with multiples cystic lesions of the thyroid revealed by neck mass and dyspnea. She underwent a subtotal thyroidectomy. The diagnosis of hydatid cyst was made preoperatively and was confirmed by histological studies. Further investigation failed to identify any other evidence of systemic hydatidosis. The patient has remained asymptomatic for 24 months after surgery. The possibility of hydatid disease, though rare, should be always kept in mind, for patients with cystic lesions of the thyroid, because a needle aspiration biopsy is a potentially harmful procedure.