IMPORTANZA CLINICA DELLA TIPIZZAZIONE SIEROLOGICA E MOLECOLARE DELLE VARIANTI DELL'ANTIGENE RhD

Il sistema Rh, dopo quello ABO, è il sistema gruppo-ematico eritrocitario più immunogeno dell’uomo. Infatti all’esecuzione del gruppo ABO si accompagna sistematicamente la contemporanea determinazione del fenotipo Rh. L’antigene più importante del sistema Rh, l’antigene D, è molto più efficace di qualunque altro antigene eritrocitario nel determinare una risposta anticorpale quando venga introdotto in un soggetto che ne è privo. Esso è presente sugli eritrociti dell’85% delle persone di razza bianca ed in percentuale ancora più alta in quelle di razza nera . Quindi dopo gli antigeni A e B, il D è il più importante nella pratica trasfusionale. Diversamente dagli antigeni A e B, tuttavia, le persone che non possiedono l’antigene D sui propri eritrociti non presentano, regolarmente, l’anti-D. La formazione dell’anticorpo anti-D origina dall’esposizione, per motivi trasfusionali o gravidanze, ad emazie che presentano l’antigene D. E’ stato stimato che dal 30 all’85% delle persone D negative che ricevono una trasfusione D positiva svilupperà l’anti-D. Per questo motivo, tutti i riceventi e tutti i donatori di sangue vengono esaminati, nelle procedure di routine, per la presenza dell’antigene D, al fine di assicurare che i riceventi D negativi vengano identificati e ricevano sangue D negativo. L’antigene D è stato da sempre oggetto di studio dell’immunoematologia. L’interesse verso tale antigene è aumentato dopo la scoperta che alcuni individui RhD positivi producevano in seguito a trasfusioni anticorpi anti-D. Successivi studi portarono alla scoperta del mosaicismo dell’antigene RhD e rivelarono la sua grande variabilità (D partial e D weak). In passato, i limiti delle metodiche sierologiche non consentirono di identificare le molte varianti dell’antigene D, che perciò venivano identificate come D negativo. Questo non rappresentava un problema nell’individuo ricevente la trasfusione, dato che veniva trasfuso con sangue RhD negativo (come riceventi alcune varianti sono tutt’ora trattate come RhD negative), ma creava un problema se l’individuo era un donatore di sangue, in quanto i soggetti D variant, possono determinare nel ricevente RhD negativo la produzione di alloanticorpi . La corretta identificazione delle varianti dell’antigene RhD è fondamentale anche per le donne gravide RhD negative, in quanto vanno sottoposte ad immunoprofilassi se il neonato è un D variant e quindi può stimolare la produzione di anticorpi che potrebbero causare una malattia emolitica del neonato (MEN) in una successiva gravidanza con feto RhD positivo. Nei servizi trasfusionali (SIT) nasce quindi l’esigenza di dover correttamente tipizzare individui che, dai test sierologici, risultano negativi, in modo da determinare possibili D variant per evitare alloimmunizzazioni da trasfusione e programmare immunoprofilassi MEN nelle donne gravide quando richiesto

Three-Dimensional Handheld Scanning to Quantify Head-Shape Changes in Spring-Assisted Surgery for Sagittal Craniosynostosis

Three-dimensional (3D) imaging is an important tool for diagnostics, surgical planning, and evaluation of surgical outcomes in craniofacial procedures. Gold standard for acquiring 3D imaging is computed tomography that entails ionizing radiations and, in young children, a general anaesthesia. Three-dimensional photographic imaging is an alternative method to assess patients who have undergone calvarial reconstructive surgery. The aim of this study was to assess the utility of 3D handheld scanning photography in a cohort of patients who underwent spring-assisted correction surgery for scaphocephaly. Pre- and postoperative 3D scans acquired in theater and at the 3-week follow-up in clinic were postprocessed for 9 patients. Cephalic index (CI), head circumference, volume, sagittal length, and coronal width over the head at pre-op, post-op, and follow-up were measured from the 3D scans. Cephalic index from 3D scans was compared with measurements from planar x-rays. Statistical shape modeling (SSM) was used to calculate the 3D mean anatomical head shape of the 9 patients at the pre-op, post-op, and follow-up. No significant differences were observed in the CI between 3D and x-ray. Cephalic index, volume, and coronal width increased significantly over time. Mean shapes from SSM visualized the overall and regional 3D changes due to the expansion of the springs in situ. Three-dimensional handheld scanning followed by SSM proved to be an efficacious and practical method to evaluate 3D shape outcomes after spring-assisted cranioplasty in individual patients and the population

The 3D skull 0–4 years: A validated, generative, statistical shape model

BACKGROUND: This study aims to capture the 3D shape of the human skull in a healthy paediatric population (0–4 years old) and construct a generative statistical shape model. METHODS: The skull bones of 178 healthy children (55% male, 20.8 ± 12.9 months) were reconstructed from computed tomography (CT) images. 29 anatomical landmarks were placed on the 3D skull reconstructions. Rotation, translation and size were removed, and all skull meshes were placed in dense correspondence using a dimensionless skull mesh template and a non-rigid iterative closest point algorithm. A 3D morphable model (3DMM) was created using principal component analysis, and intrinsically and geometrically validated with anthropometric measurements. Synthetic skull instances were generated exploiting the 3DMM and validated by comparison of the anthropometric measurements with the selected input population. RESULTS: The 3DMM of the paediatric skull 0–4 years was successfully constructed. The model was reasonably compact - 90% of the model shape variance was captured within the first 10 principal components. The generalisation error, quantifying the ability of the 3DMM to represent shape instances not encountered during training, was 0.47 mm when all model components were used. The specificity value was <0.7 mm demonstrating that novel skull instances generated by the model are realistic. The 3DMM mean shape was representative of the selected population (differences <2%). Overall, good agreement was observed in the anthropometric measures extracted from the selected population, and compared to normative literature data (max difference in the intertemporal distance) and to the synthetic generated cases. CONCLUSION: This study presents a reliable statistical shape model of the paediatric skull 0–4 years that adheres to known skull morphometric measures, can accurately represent unseen skull samples not used during model construction and can generate novel realistic skull instances, thus presenting a solution to limited availability of normative data in this field

Correlation between head shape and volumetric changes following spring-assisted posterior vault expansion

OBJECTIVE: To investigate whether different head shapes show different volumetric changes following spring-assisted posterior vault expansion (SA-PVE) and to investigate the influence of surgical and morphological parameters on SA-PVE. MATERIALS AND METHODS: Preoperative three-dimensional skull models from patients who underwent SA-PVE were extracted from computed tomography scans. Patient head shape was described using statistical shape modelling (SSM) and principal component analysis (PCA). Preoperative and postoperative intracranial volume (ICV) and cranial index (CI) were calculated. Surgical and morphological parameters included skull bone thickness, number of springs, duration of spring insertion and type of osteotomy. RESULTS: In the analysis, 31 patients were included. SA-PVE resulted in a significant ICV increase (284.1 ± 171.6 cm3, p<0.001) and a significant CI decrease (−2.9 ± 4.3%, p<0.001). The first principal component was significantly correlated with change in ICV (Spearman ρ = 0.68, p<0.001). Change in ICV was significantly correlated with skull bone thickness (ρ = −0.60, p<0.001) and age at time of surgery (ρ = −0.60, p<0.001). No correlations were found between the change in ICV and number of springs, duration of spring insertion and type of osteotomy. CONCLUSION: SA-PVE is effective for increasing the ICV and resolving raised intracranial pressure. Younger, brachycephalic patients benefit more from surgery in terms of ICV increase. Skull bone thickness seems to be a crucial factor and should be assessed to achieve optimal ICV increase. In contrast, insertion of more than two springs, duration of spring insertion or performing a fully cut through osteotomy do not seem to impact the ICV increase. When interpreting ICV increases, normal calvarial growth should be taken into account

Evaluation of Swallow Function in Patients with Craniofacial Microsomia: A Retrospective Study

Craniofacial microsomia (CFM) is characterized by underdevelopment of the structures derived from the first and second pharyngeal arches resulting in aesthetic, psychological, and functional problems including feeding and swallowing difficulties. The aim of this study is to gain more insight into swallowing difficulties in patients with CFM. A retrospective study was conducted in the population of patients diagnosed with CFM at three major craniofacial units. Patients with feeding difficulties and those who underwent video fluoroscopic swallow (VFS) studies were included for further analyses. The outcome of the VFS-studies was reviewed with regard to the four phases of swallowing. In our cohort, 13.5% of the 755 patients were diagnosed with swallowing difficulties. The outcome of the VFS-studies of 42 patients showed difficulties in the oral and pharyngeal phases with both thin and thick liquids. Patients with more severe mandibular hypoplasia showed more difficulties to form an appropriate bolus compared to patients who were less severely affected. This is the first study to document swallowing problems in patients with CFM. Difficulties were seen in both the oral and pharyngeal phases. We recommend routine screening for swallowing issues by a speech and language therapist in all patients with CFM and to obtain a VFS-study in patients with a type III mandible

Assessing the health and development of ART-conceived young adults: A study of feasibility, parent recall, and acceptability

<p>Abstract</p> <p>Background</p> <p>Assisted reproductive technologies (ART) to treat infertility have been available for nearly three decades. There have been a number of systematic comparisons of the health and development of ART-conceived with spontaneously-conceived (SC) children. Data are equivocal, some finding no differences and others that there are more health and developmental problems in the ART group. It is agreed that perinatal mortality and morbidity are worse after assisted than spontaneous conception and the impact of the hormonally altered intrauterine environment on puberty and later fertility of offspring are unknown. To date however, there has been no investigation of the health and development of ART-conceived young adults, including from the world's few prospective cohorts of ART conceived children. Obtaining these data requires contact to be made with people at least twenty years after discharge from the treating service. Given the ethical difficulties of approaching families to participate in research up to two decades after cessation of treatment, the aim of this exploratory qualitative investigation was to assess the feasibility and acceptability of approaching mothers treated for infertility prior to 1988, and their recall of the health and development of their ART-conceived young adult children.</p> <p>Methods</p> <p>Mothers treated for infertility at the Royal Women's Hospital Reproductive Biology Unit in Melbourne, Australia prior to 1988 were approached by a senior clinician and invited to participate in individual semi-structured interviews which could include their partners and/or young adult children if they wished. Recruitment continued until theoretic saturation had been reached.</p> <p>Results</p> <p>Ten mothers, two of their husbands and five young adults participated in interviews, and the health and development of 15 ART-conceived young adults were described. The experience of conception, pregnancy, birth and the health and development of the children were recalled vividly and in detail. Families were pleased to have been approached and supported the need for systematic data collection. Mode of conception had been disclosed from childhood to all the offspring.</p> <p>Conclusion</p> <p>With careful and sensitive recruitment strategies it is feasible and acceptable to contact women treated for infertility at least two decades ago and their families, to assess the health and development of ART-conceived young adults.</p

H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

BACKGROUND: Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge. METHODS: We used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus. RESULTS: Passive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be ≤1∶11 for all immune sera, independently of source species. CONCLUSIONS: These data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines