Early posterior vitreous detachment is associated with LAMA5 dominant mutation

Background: Extracellular matrix molecular components, previously linked to multisystem syndromes include collagens, fibrillins and laminins. Recently, we described a novel multisystem syndrome caused by the c.9418G>A p.(V3140M) mutation in the laminin alpha-5 (LAMA5) gene, which affects connective tissues of all organs and apparatus in a three generation family. In the same family, we have also reported a myopic trait, which, however, was linked to the Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) gene. Results of investigation on vitreous changes and their pathogenesis are reported in the present study.Materials and Methods: Nineteen family individuals underwent complete ophthalmic examination including best-corrected visual acuity (BCVA), fundus examination, fundus photography, intraocular pressure measurement, axial length measurement using ocular biometry, Goldmann visual field examination, standard electroretinogram, SD-OCT. Segregation analysis of LAMA5 and P4HA2 mutations was performed in enrolled members.Results: The vitreous alterations fully segregated with LAMA5 mutation in both young and adult family members. Slight reduction of retinal thickness and peripheral retinal degeneration in only two patients were reported.Conclusions: In this work we showed that PVD is a common trait of LAMA5 multisystem syndrome, therefore occurring as an age-unrelated trait. We hypothesize that the p.(V3140M) mutation results in a reduction of retinal inner limiting membrane (ILM) stability, leading to a derangement in the macromolecular structure of the vitreous gel, and PVD. Further investigations will be necessary to elucidate the role of wild type and mutated LAMA5 in the pathogenesis of PVD.     

Five-year clinical outcomes using the bioresorbable vascular scaffold: Insights from the FRANCE ABSORB registry

Central illustration: cumulative major adverse cardiac events (MACE) and bioresorbable vascular scaffold (BVS) thrombosis rates after 1, 2, 3, 4 and 5 years.

     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

Cleaning,Shaping, and Disinfecting Abilities of 2 Instrument Systems as Evaluated by a Correlative Micro–computed Tomographic and Histobacteriologic Approach

IntroductionThis study assessed the cleaning, shaping, and disinfection abilities of 2 instrumentation systems in molar root canals using a novel correlative analytical approach.MethodsThe root canals from extracted mandibular and maxillary molars with apical periodontitis were pair matched according to anatomic similarities as determined by micro–computed tomographic analysis and prepared with either XP-endo Shaper (FKG Dentaire, La Chaux-de-Fonds, Switzerland) (n = 16) or Reciproc Blue (VDW, Munich, Germany) (n = 16) instruments and 2.5% sodium hypochlorite irrigation. Pre- and postpreparation micro–computed tomographic scans were used to identify and calculate the unprepared surface areas (shaping), which were histobacteriologically evaluated for the presence of residual bacteria (disinfection) and pulp tissue remnants (cleaning) in each canal third.ResultsUnprepared canal surface areas for XP-endo Shaper and Reciproc Blue in the full canal length were approximately 26% and 19% (P < .05), respectively (30% and 23% in the apical part of the canal, P > .05). Preparation with Reciproc Blue resulted in 37.5% canals free of bacteria in all sections examined and 56% in the apical sections only. XP-endo Shaper resulted in 44% canals free of bacteria in all sections, and 56% in the apical part of the canal only. Pulp tissue remnants were not observed in 31% (all canal sections) and 50% (apical canal sections) of specimens from both instrument systems. No significant differences were observed between instruments when comparing the amount of pulp tissue remnants and the number of cases negative for bacteria and tissue remnants (P > .05).ConclusionsAlthough the Reciproc Blue instrument had superior shaping ability in comparison with XP-endo Shaper, both systems performed similarly in cleaning and disinfecting root canals. Irregular canals and difficult-to-reach areas were not thoroughly cleaned and disinfected by any of the tested systems.     

Retrograde Instrumentation of Surgically Resected Roots Using Controlled Memory Files: A Human Cadaver Study

IntroductionThe purpose of this study is to evaluate the amount of residual obturation material of retroinstrumented surgically resected roots using controlled memory files and to evaluate the incidence of adverse treatment outcomes.MethodsThirty maxillary anterior teeth in human cadavers were selected, and nonsurgical root canal treatment was performed on these teeth. A standardized 4-mm osteotomy and a 3-mm root resection with as close to 0° bevel as possible were made on each tooth. A microsurgical diamond tip was used to create a 1- to 2-mm starting point for each retropreparation. A 25/06 and 30/06 VTaper 2H were bent at about 90° angle to mimic the clinical and anatomic restrictions and used to create a retropreparation to a depth of 14 mm. Micro–computed tomography scans were taken and analyzed for volume and percentage of residual obturation material at 5 and 10 mm. In addition, the incidences of instrument separation and crack and ledge formation in the teeth were recorded.ResultsThe median volume of residual obturation at 5 and 10 mm was 0.18 mm³ (interquartile range, 0.36 mm³) and 1.97 mm³ (interquartile range, 1.99 mm³), respectively. The overall incidence of file separation during retropreparation was 13.33% (4/30). Among the cases analyzed with micro–computed tomography, none showed crack or ledge formation.ConclusionsRetroinstrumentation of surgically resected roots using controlled memory files cleans the canal effectively with relatively low adverse treatment outcomes. Although this novel technique is limited in application, it is a safe and effective way to achieve a deep, clean retropreparation.     

The Lausanne forensic pathology approach to post-mortem imaging for natural and non-natural deaths

Post-mortem imaging by computed tomography (PMCT) and post-mortem CT angiography (PMCTA) are used routinely in forensic practice as components to the autopsy. PMCT is efficient for gas detection, foreign body visualization and skeleton analysis. Various parameters can lead to the indication for contrast agent injection. Contrast injection into the vascular system can overcome the disadvantages of non-contrast PMCT by visualization of solid organ parenchyma and vessels. This can also assist the conventional autopsy, allowing one to investigate the vascular system. It is the method of choice for the analysis of the blood vessels by showing vascular pathology, congenital or postsurgical anatomical variations and an exact source of bleeding. By knowing the artefacts linked to the angiographic technique, we limit the risk of misinterpretation. The use of post-mortem MRI (PMMR) for diagnostic purposes is still limited to rare indications. These include review of the neck in cases of death by mechanical asphyxia, total-body PMMR in neonatal and pediatric death and cardiac PMMR in case of suspected myocardial infraction. Currently, in our daily practice, the vast majority or PMMR is only performed for research purposes.     

The Effect of Helicobacter pylori on Gastric Cancer Treated with Adjuvant Chemotherapy After Curative Resection

Helicobacter pylori has been associated with diverse pathologies of varying severity. We investigated the H. pylori infection status and its association with the pathologic features and clinical outcomes in stage III gastric cancer patients treated with adjuvant therapy after curative resection. Between 2004 and 2009, the records of 76 consecutive patients were retrospectively reviewed. H. pylori infection was confirmed by examination of pathological specimen. The relationship between H. pylori and the clinicopathological features was analyzed by Fisher exact test, Student’s t test, and Kaplan-Meier method. Of the 76 patients, 16 patients (21.1 %) were confirmed for H. pylori infection. The median age was 59 years. Twenty-three patients received chemotherapy and remainder received chemoradiotherapy. H. pylori status did not correlate with the clinicopathologic features. It was greater in non-neoplastic tissue than the tumor tissue (21.1 vs 7.9 %). Median follow-up was 21 months. During this period, 88.2 % patients had experienced tumor recurrence, and 85.5 % patients had died. Recurrence was observed in 87.5 % patients and in 88.3 % patients in H. pylori-positive and H. pylori-negative patients, respectively (P = 0.92). Disease-free survival was 28.4 ± 7.9 months and overall survival was 31.5 ± 7.4 months in H. pylori-positive patients compared with 28.3 ± 3.7 and 33.2 ± 3.4 months, respectively, in H. pylori-negative patients. H. pylori infection status did not have effect on the overall or disease-free survival (p = 0.85 and P = 0.86), respectively. H. pylori status might not be useful as a prognostic and predictive factor for clinical outcomes.