Results of an international survey on the investigation and endovascular management of cerebral vasospasm and delayed cerebral ischemia

Background: Delayed cerebral ischemia (DCI) is a major cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage. Endovascular management of this condition offers a new hope in preventing adverse outcome; however, a uniform standard of practice is lacking owing to a paucity of clinical trials. We conducted an international survey on the use of investigative and endovascular techniques in the treatment of DCI to assess the variability of current practice. Methods: Neurovascular neurosurgeons and neuroradiologists were contacted through professional societies from America, United Kingdom, Europe, and Australasia. Members were invited to complete a 13-item questionnaire regarding screening techniques, first-line and second-line therapies in endovascular intervention, and the role of angioplasty. Answers were compared using χ2 testing for nonparametric data. Results: Data from 344 respondents from 32 countries were analyzed: 167 non-United States and 177 U.S. respondents. More than half of all clinicians had 10+ years of experience in units with a mixture of higher and lower case volumes. Daily transcranial Doppler ultrasonography was the most commonly used screening technique by both U.S. (70%) and non-U.S. (53%) practitioners. Verapamil was the most common first-line therapy in the United States, whereas nimodipine was most popular in non-U.S. countries. Angioplasty was performed by 83% of non-U.S. and 91% of U.S. clinicians in the treatment of vasospasm; however, more U.S. clinicians reported using angioplasty for distal vasospasm. Conclusions: Treatment practices for DCI vary considerably, with the greatest variability in the choice of agent for intra-arterial therapy. Our data demonstrate the wide variation of approaches in use at present. However, without further clinical trials and development of a uniform standard of best practice, variability in treatment and outcome for DCI is likely to continue

Ovarian Torsion in the Third Trimester of Pregnancy Leading to Iatrogenic Preterm Delivery

Ovarian torsion in the third trimester of pregnancy leading to a midline laparotomy and caesarean section for the delivery of a preterm baby is an uncommon event. As the woman is likely to present with nonspecific symptoms of lower abdominal pain, nausea, and vomiting, ovarian torsion can often be misdiagnosed as appendicitis or preterm labour. Treatment and the opportunity to preserve the tube and ovary may consequently be delayed. We report the case of a multiparous woman who had undergone two previous caesarean sections at term, presenting at 35 weeks of gestation with a presumptive diagnosis of acute appendicitis. Ultrasonography described a cystic lesion 6 × 3 cm in the right adnexa, potentially a degenerating fibroid or a torted right ovary. MRI of the pelvis was unable to provide further clarity. The patient was managed by midline laparotomy and simultaneous detorsion of the ovarian pedicle and ovarian cystectomy together with caesarean section of a preterm infant. This report describes that prompt recognition and ensuring intraoperative access can achieve a successful maternal and fetal outcome in this rare and difficult scenario. Furthermore, we would like to emphasise that the risk for a pregnant woman and her newborn could be reduced by earlier diagnosis and management of ovarian masses (Krishnan et al., 2011)

Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy

Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability

Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy

Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability

The epidemiology and natural history of papillomavirus infection of the cervix uteri

The epidemiology of cervical cancer indicates that some sexually transmitted agent is responsible and Human papillomavirus (HPV) is the currently favoured agent. This study was designed to assess whether HPV 16 could be identified by filter in-situ hybridisation (FISH) in the normal cervix and, if present, whether the woman was placed at an increased risk of developing cervical neoplasia. To examine this question, 1412 women, attending for routine cervical cytology, were studied. HPV 16 DNA was found in the cervical scrapes in 23% of this population when assayed by FISH. There was no difference in the positivity rates between those with normal or abnormal cytology. A group of women (427) from this cohort, who were all cytologically normal, were colposcoped and a significant association between cervical disease, missed by cytology, and HPV16 positivity was found (p = 0.01). A follow-up case control study of those with a normal cervix with or without HPV16 DNA was conducted. Regular review over the ensuing 2 years with repeat cytology, colposcopy and FISH was undertaken. Only nine of these women developed any evidence of CIN over this period and this was not associated with HPV16 DNA. The epidemiologic factors were also compared between the cases and the controls. 162 cervical scrapes were used to compare the FISH method with Southern blotting and a weak association was found (Kappa=0.32), indicating the limitations of FISH for this type of study. The serial FISH results from each colposcopy clinic visit were assessed and also showed weak association

Ovarian Torsion in the Third Trimester of Pregnancy Leading to Iatrogenic Preterm Delivery

Ovarian torsion in the third trimester of pregnancy leading to a midline laparotomy and caesarean section for the delivery of a preterm baby is an uncommon event. As the woman is likely to present with nonspecific symptoms of lower abdominal pain, nausea, and vomiting, ovarian torsion can often be misdiagnosed as appendicitis or preterm labour. Treatment and the opportunity to preserve the tube and ovary may consequently be delayed. We report the case of a multiparous woman who had undergone two previous caesarean sections at term, presenting at 35 weeks of gestation with a presumptive diagnosis of acute appendicitis. Ultrasonography described a cystic lesion 6 × 3 cm in the right adnexa, potentially a degenerating fibroid or a torted right ovary. MRI of the pelvis was unable to provide further clarity. The patient was managed by midline laparotomy and simultaneous detorsion of the ovarian pedicle and ovarian cystectomy together with caesarean section of a preterm infant. This report describes that prompt recognition and ensuring intraoperative access can achieve a successful maternal and fetal outcome in this rare and difficult scenario. Furthermore, we would like to emphasise that the risk for a pregnant woman and her newborn could be reduced by earlier diagnosis and management of ovarian masses (Krishnan et al., 2011)

Cytology in the diagnosis of cervical cancer in symptomatic young women: a retrospective review

This work was supported by Cancer Research UK [C8162/A16892]

Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy

International audienceEmbryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability