Is magnesium neuroprotective following global and focal cerebral ischaemia? A review of published studies.

Neuroprotective activity with magnesium associated with animal models of cerebral ischaemia, seizure, perinatal hypoxia/ischaemia, subarachnoid haemorrhage and traumatic brain injury has provided the justification for clinical stroke trials. However, the recent IMAGES stroke clinical trial found magnesium to be largely ineffective. Hence, due to the negative stroke trial outcome, current FAST-MAG trial and our own experience with magnesium in cerebral ischaemia animal models, we thought it prudent to review these preclinical and clinical studies. We reviewed nine studies describing the use of magnesium following global cerebral ischaemia and fourteen following focal cerebral ischaemia. Four global ischaemia and six focal ischaemia studies did not show a significant neuroprotective effect with magnesium. In the majority of positive magnesium studies animal body temperature was not monitored post-ischaemia. Thus the effects of post-ischaemic hypothermia cannot be ruled out as a confounding factor in positive magnesium cerebral ischaemia studies. Moreover, data from our own laboratory indicates that magnesium is only neuroprotective when combined with post-ischaemic hypothermia. These data provide a possible explanation of why the IMAGES trial was largely unsuccessful, as current stroke patient management does not involve hypothermia induction. Future preclinical and clinical cerebral ischaemia trials with magnesium should consider combining treatment with mild hypothermia.     

Free anterolateral thigh flap versus free forearm flap: Functional results in oral reconstruction.

Nowadays, microsurgery performed for oral reconstruction of cancer patients, has become the standard treatment in restoring oral functions. The free radial forearm flap (FRFF) is still apparently the first reconstructive choice in oral cavity cancers. Recently the anterolateral thigh flap (ALTF) seemed to challenge the superiority of FRFF. The lack of functional data on which to base this recent supposition is the reason for this new research. Twenty reconstructed patients were enrolled for this study. Speech, swallowing, and donor site complications were studied to assess differences between the two techniques. Results show that difference in function between ALTF and FRFF groups is statistically insignificant. Donor site risks and complications seem to be the only variables among groups. These variables may be used as indicators when making a surgical choice.     

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies

Marfan Syndrome (MFS) is an autosomal dominant disorder of the connective tissue due to mutations of Fibrillin-1 gene (FBN1) in more than 90% of cases and Transforming Growth Factor-Beta-Receptor2 gene (TGFB2R) in a minority of cases. Genotyping is relevant for diagnosis and genotype-phenotype correlations. We describe the FBN1 genotypes and related phenotypes of 81 patients who were referred to our attention for MFS or Marfan-like phenotypes. Patients underwent multidisciplinary pertinent evaluation in the adult or paediatric setting, according to their age. The diagnosis relied on Ghent criteria. To optimise DHPLC analysis of the FBN1 gene, all coding regions of the gene were directly sequenced in 19 cases and 10 controls: heterozygous amplicons were used as true positives. DHPLC sensitivity was 100%. Then, DHPLC was used to screen 62 other cases. We identified 74 FBN1 mutations in 81 patients: 64 were novel and 17 known. Of the 81 mutations, 41 were missense (50.6%), 27, either nonsense or frameshift mutations and predicted a premature termination codon (PTC) (33%), 11 affected splice sites (13.6%), and two predicted in-frame deletions (2.5%). Most mutations (67.9%) occurred in cbEGF-like modules. Genotype was clinically relevant for early diagnosis and conclusion of the diagnostic work-up in patients with incomplete or atypical phenotypes.     

Anatomic variations of surgical importance in ethmoid labyrinth and sphenoid sinus. A study of radiological anatomy

Summary The present study was performed on axial and coronal CT scans of 100 patients, most of whom were affected by nasal polyposis. Five observers had to analyse the radiograms and answer a questionnaire including the following items: presence of a supraorbital recess; identification of anterior and posterior ethmoidal canals; dehiscences in the lamina papyracea; pneumatized middle turbinate; presence of a spheno-maxillary plate; presence of Haller's cells; presence of Onodi's cells; relationships of the optic canal; relationships of the internal carotid artery; relationships of the maxillary nerve; relationships of the vidian nerve; level difference between the ethmoid roof and nasal vault; depth of the sphenoethmoidal recess. The data obtained were compared with those drawn from anatomical studies. The fair agreement between them proves the value of CT as an alternative method for studying paranasal sinuses anatomy.

---

Anatomie radiologique des variations du labyrinthe ethmoïdal et du sinus sphénoïdal et leurs conséquences chirurgicales

Résumé Cette étude a été réalisée sur 100 patients dont la plupart présentait une polypose nasale étudiée en coupes T D M axiale et coronale. Cinq lecteurs ont revu les clichés et répondu au questionnaire suivant: présence d'un récessus supra orbitaire; identification des canaux ethmoïdaux antérieur et postérieur; déhiscence de la lame papyracée; pneumatisation du cornet moyen; présence d'un plateau sphéno maxillaire; présence de cellules de Haller; présence de cellules d'Onodi; rapports du canal optique; rapports de l'artère carotide interne; rapports du nerf maxillaire; rapports du nerf vidien; dénivelé entre le toit ethmoïdal et le toit nasal; profondeur du récessus sphéno-ethmoïdal. Les données obtenues ont été comparées avec celles provenant de travaux anatomiques. La concordance acceptable entre les deux démontre la valeur du scanner comme méthode d'étude alternative de l'anatomie des sinus para nasaux.

     

Employing a systematic approach to biobanking and analyzing clinical and genetic data for advancing COVID-19 research

Within the GEN-COVID Multicenter Study, biospecimens from more than 1000 SARS-CoV-2 positive individuals have thus far been collected in the GEN-COVID Biobank (GCB). Sample types include whole blood, plasma, serum, leukocytes, and DNA. The GCB links samples to detailed clinical data available in the GEN-COVID Patient Registry (GCPR). It includes hospitalized patients (74.25%), broken down into intubated, treated by CPAP-biPAP, treated with O₂ supplementation, and without respiratory support (9.5%, 18.4%, 31.55% and 14.8, respectively); and non-hospitalized subjects (25.75%), either pauci- or asymptomatic. More than 150 clinical patient-level data fields have been collected and binarized for further statistics according to the organs/systems primarily affected by COVID-19: heart, liver, pancreas, kidney, chemosensors, innate or adaptive immunity, and clotting system. Hierarchical clustering analysis identified five main clinical categories: (1) severe multisystemic failure with either thromboembolic or pancreatic variant; (2) cytokine storm type, either severe with liver involvement or moderate; (3) moderate heart type, either with or without liver damage; (4) moderate multisystemic involvement, either with or without liver damage; (5) mild, either with or without hyposmia. GCB and GCPR are further linked to the GCGDR, which includes data from whole-exome sequencing and high-density SNP genotyping. The data are available for sharing through the Network for Italian Genomes, found within the COVID-19 dedicated section. The study objective is to systematize this comprehensive data collection and begin identifying multi-organ involvement in COVID-19, defining genetic parameters for infection susceptibility within the population, and mapping genetically COVID-19 severity and clinical complexity among patients.Subject terms: Genetics research, Viral infection     

Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.