Population-based germline breast cancer gene association studies and meta-analysis to inform wider mainstream testing.

BACKGROUND: Germline genetic testing, previously restricted to familial and young-onset breast cancer, is now offered increasingly broadly to 'population-type' breast cancer patients in mainstream oncology clinics, with wide variation in the genes included. METHODS: Weighted meta-analysis was performed for three population-based case-control studies (BRIDGES, CARRIERS and UK Biobank) comprising in total 101,397 women with breast cancer and 312,944 women without breast cancer, to quantify for 37 putative breast cancer susceptibility genes (BCSGs) the frequency of pathogenic variants (PVs) in unselected, 'population-type' breast cancer cases and their association with breast cancer and its subtypes. RESULTS: Meta-analysed odds ratios (ORs) and frequencies of PVs in population-type breast cancer cases were generated for BRCA1 (OR= 8.73 (95% CI 7.47-10.20), 1 in 101), BRCA2 (OR=5.68 (5.13-6.30), 1 in 68) and PALB2 (OR= 4.30 (95% CI 3.68-5.03), 1 in 187). For both CHEK2 (OR=2.40 (95% CI 2.21-2.62), 1 in 73) and ATM (OR=2.16 (95%CI 1.93-2.41), 1 in 132) subgroup analysis showed stronger association with ER-positive disease. Magnitude of association and frequency of PVs were low for RAD51C (OR=1.53 (95%CI 1.15-2.04), 1 in 913), RAD51D (OR=1.76, (95%CI 1.15-2.41, 1 in 1079) and BARD1 (OR=2.34 (1.85-2.97), 1 in 672); frequencies and associations were moderately higher restricting to triple-negative breast cancers The PV-frequency in 'population-type' breast cancer cases was very low for 'syndromic' BCSGs TP53 (1 in 1844), STK11 (1 in 11,525), CDH1 (1 in 2668), PTEN (1 in 3755) and NF1 (1 in 1470), with metrics of association also modest ranging from OR=3.62 (95%CI 1.98-6.61) for TP53 down to OR=1.60 (95%CI 0.48-5.30) for STK11. CONCLUSIONS: These metrics reflecting 'population-type' breast cancer will be informative to defining the appropriate gene set as we continue to expand to germline testing out to more unselected population-type breast cancer cases.

Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

Programmed intermittent epidural bolus regimen vs continuous epidural infusion: a retrospective study of motor block and obstetric outcomes using the Robson's Ten Group Classification System.

BACKGROUND: Use of a programmed intermittent epidural bolus (PIEB) regimen during labour is associated with several benefits over a continuous epidural infusion (CEI), including reduced local anaesthetic consumption and reduced risk of motor block. We hypothesise that the benefits of a PIEB regimen may vary according to the Robson Ten Group Classification System (TGCS). The aim of this study was to determine if introduction of a PIEB regimen was associated with reduced incidence of motor block. We also wished to examine changes in obstetric outcomes following PIEB introduction across the Robson TGCS. METHODS: This was a single-centre retrospective cohort study. Data were collected over two three-month periods before and after PIEB introduction. The primary outcome was the incidence of motor block. Maternal and obstetric outcomes across Robson Groups 1-4 were analysed. RESULTS: Introduction of PIEB was associated with reduced incidence of motor block (28.4% (95% CI 25.7% to 31.3%) vs 22.4%, (95% CI 19.9% to 25.2%), difference 5.9% (95% CI 1.0% to 21.1%), P=0.003), with no association with changes in rates of caesarean section, operative vaginal delivery or other obstetric outcomes. Use of a PIEB regimen was associated with reduced incidence of motor block in Robson Group 4a (20.3% (16.0%, 28.0%) vs 12.0%, (7.6%, 16.4%), difference 9.9% (95% CI -17.4% to -2.4%) P=0.009). There were no significant changes in other outcomes assessed across Robson TGCS. CONCLUSION: Introduction of PIEB for maintenance of labour analgesia was associated with reduced incidence of motor block in our institution compared with CEI. Presenting results according to Robson's TGCS in future studies may allow better elucidation of the impact of neuraxial analgesia on maternal and obstetric outcomes.

Model matters: Differential outcomes in traumatic optic neuropathy pathophysiology between blunt and blast-wave mediated head injuries.

Over 3 million people in the United States live with long-term disability because of a traumatic brain injury (TBI). The purpose of this study was to characterize and compare two different animal models of TBI (blunt head trauma and blast TBI) to determine common and divergent characteristics of these models. With recent literature reviews noting the prevalence of visual system injury in animal models of TBI, coupled with clinical estimates of 50-75% of all TBI cases, we decided to assess commonalities, if they existed, through visual system injury. A unilateral (left directed) blast and repeat blast model injury with coup-contra-coup injury patterns were compared to a midline blunt injury. Injuries were induced in adult male mice to observe and quantify visual deficits. Retinal ganglion cell loss and axonal degeneration in the optic tract, superior colliculus, and lateral geniculate nuclei were examined to trace injury outcomes throughout major vision-associated areas. Optokinetic response, immunohistochemistry, and western blots were analyzed. Where a single blunt injury produces significant visual deficits a single blast injury appears to have less severe visual consequences. Visual deficits after repeat blasts are similar to a single blast. Single blast injury induces contralateral damage to the right optic chiasm and tract whereas bilateral injury follows a single blunt TBI. Repeat blast injuries are required to see degeneration patterns in downstream regions similar to the damage seen in a single blunt injury. This finding is further supported by amyloid precursor protein (APP) staining in injured cohorts. Blunt injured groups present with staining 1.2 mm ahead of the optic nerve, indicating axonal breakage closer to the optic chiasm. In blast groups, APP was identifiable in a bilateral pattern only in the geniculate nucleus. Evidence for unilateral neuronal degeneration in brain tissue with bilateral axonal ruptures are pivotal discoveries in this model differentiation. Analysis of the two injury models suggests that there is a significant difference in the histological outcomes dependent on injury type, though visual system injury is likely present in more cases than are currently diagnosed clinically.

Productive performance, breast growth and digestive system development in European quail subjected to post-hatch fasting for different periods.

This study assessed the effect of different periods of post-hatch fasting on animal performance and breast and digestive system growth in European quail. Quail chicks were distributed in a completely randomized design, with four fasting periods (0, 24, 36, and 48 hs) and four replications of 40 birds per treatment. In 1 to 14-day-old chicks, weight gain decreased with increasing fasting time. Compensatory gain was observed from 15 days of age onward. Fasted quail had a lower length and relative weight of the digestive system than fed animals for up to 14 days. Histologically, the duodenal villus height was significantly lower in 3-day-old quail fasted for 36 hs than in those fasted for 48 hs, but this effect was not observed at 7 days. Scanning electron microscopy showed no differences in the small intestinal mucosa between fasted and fed birds at 3 days of age. Post-hatch fasting reduced the relative weight of the breast in quail aged 1 to 14 days but did not affect type IIa and IIb fiber diameter at 35 days. On the basis of these results, it is recommended that European quail raised for meat should not be fasted for more than 48 hs post-hatch.

Effect of spineless cactus [Nopalea cochenillifera (L.) Salm Dyck] on nutrient intake, ingestive behaviour, and performance of lambs.

The objective of this study was to evaluate the effect of increasing levels of spineless cactus (SC) [Nopalea cochenillifera (L.) Salm Dyck] on nutrient intake, ingestive behaviour, and performance of lambs in a feedlot. Thirty-two male (non-castrated) Santa Inês lambs with a mean initial body weight (BW) of 20.4 ± 2.60 kg were distributed across four levels of spineless cactus: zero, 24, 52, and 75% of total diet dry matter (DM). Over 56 days, the animals had their intake and performance monitored. The inclusion of SC influenced (p<0.05) in a quadratic way the dry matter intake and total digestible nutrients, but linearly decreased (p<0.05) the neutral detergent fiber intake. Drinking water intake decreased linearly (p<0.05) with the inclusion of SC in the diet. The inclusion of SC influenced (p<0.05) in a quadratic way the digestibility of organic matter in the diet. The increase in the level of SC in the diet increased linearly (p<0.05) the feeding and rumination efficiencies of the lambs. The maximum daily gain of 0.237 kg/day was achieved with 44% SC in the diet. It is recommended to include up to 40% of spineless cactus in the diet of lambs.

Occurrence of mercury in polychaete species (Annelida) and their associated sediments from an important Southern Atlantic Ocean Bay.

In the present study, the Hg levels in freshly collected polychaete species and their associated sediments were evaluated from Todos os Santos Bay, Northeastern Brazil. Additionally, it was also measured the Hg distribution along the annelids' body parts (anterior region, abdomen, and posterior region). Total Hg concentration was as follows: 13.6-144 µg kg-1 (Scolelepis chilensis, deposit feeder), 8.2-122 µg kg-1 (Laeonereis acuta, deposit feeder), 95-612 µg kg-1 (Armandia agilis, deposit feeder); 96.6-206 µg kg-1 (Lumbrineris sp., carnivorous), 75.3-112 µg kg-1 (Goniada echinulate, carnivorous), and 115-198 µg kg-1 (Branchiomma sp., suspension feeder). In turn, Hg levels in sediments ranged from 2.77 ± 0.24 to 6.38 ± 0.15 µg kg-1. Hg concentrations found in polychaete soft tissues were higher than those found in the sediments. Specific habits, feeding behavior, trophic level, and stressful environmental conditions are the main factors affecting the Hg levels in the species studied. The bioaccumulation factor (BAF), contamination factor (CF), and ecological risk assessment (Er) were calculated. The BAF values were higher than 1 for all studied species, indicating Hg bioaccumulation in the annelids, but the low levels of CF e Er showed those Hg levels present low to no significant ecological risk for the biota and benthonic organisms living in the sediments. Finally, no statistically significant difference was observed for Hg concentration levels along the polychaete body parts.

NMR-Based Metabolomic Approach for Evaluation of the Harvesting Time and Cooking Characteristics of Different Cassava Genotypes.

Cassava is an important staple food for low-income countries. However, its cooking characteristics are especially affected by genotype. In this study, two groups of genotypes, namely hard to cook (HTC) and easy to cook (ETC), were harvested at different times (9 and 15 months), and evaluated by NMR coupled to chemometrics. Additionally, lignin of these materials was studied by 1H-13C HSQC NMR. The carbohydrates were the most important class of compounds to differentiate the cassava genotypes. The correlation of NMR with cooking time and starch content showed that the higher content of primary metabolites, mostly glucose, can be associated with longer cooking times and reduction of starch, corroborating the metabolic pathways analysis. Furthermore, it was observed that the lignin from cell walls did not differentiate the cooking performance of the genotypes.

Determining the appropriate use of Technology Enabled Care Services (TECS) to manage upper-limb trauma injuries during the COVID-19 pandemic: A multicentre retrospective observational study.

BACKGROUND: The COVID-19 pandemic created a unique opportunity to explore the use of Technology Enabled Care Services (TECS), which remains novel for many service providers. This study assesses the factors that affect adaptation to remote monitoring of patients after upper-limb trauma injury. A standardised risk-stratified screening tool is further developed here to support clinical staff in both the determination of appropriate use of TECS and the optimisation of patient care. OBJECTIVES: 1: To explore the patient and injury factors that determine the appropriate use of TECS for patients with upper-limb injury. 2: To use these findings to refine a standardised screening tool for the appropriate choice of follow-up format. METHODS: A retrospective review of patient management was undertaken across three NHS upper-limb trauma units during the first UK COVID-19 lockdown. Data were collected, and themes were analysed across a number of predetermined categories. This was underpinned by a review of contemporary policy guidance and literature. RESULTS: A total of 85% of patients were offered an appropriate format of follow-up; this was defined by the ability to achieve desired patient-clinician goals and lack of complications. Key factors in determining appropriate follow-up included extent of injury, mental health considerations, and the need for face-to-face (F2F) assessment and treatment. CONCLUSION: Study findings demonstrate consistency between units in the factors determining the appropriate use of TECS. The refined screening tool provides a risk-stratified, standardised approach to the choice of follow-up format, F2F or TECS. It is hoped that this will support future clinical decision-making processes to ensure optimal patient care.

Citywide Integrated Aedes aegypti Mosquito Surveillance as Early Warning System for Arbovirus Transmission, Brazil.

Arbovirus epidemiology lacks efficient and timely surveillance systems with accurate outbreak alert signals. We devised a citywide integrated surveillance system combining entomologic, epidemiologic, and entomo-virologic data gathered during 2017-2020 in Foz do Iguaçu, Brazil. We installed 3,476 adult mosquito traps across the city and inspected traps every 2 months. We compared 5 entomologic indices: traditional house and Breteau indices for larval surveys and trap positivity, adult density, and mosquitoes per inhabitant indices for adult trapping. We screened for dengue, Zika, and chikungunya viruses in live adult Aedes aegypti mosquitoes collected from traps. Indices based on adult mosquito sampling had higher outbreak predictive values than larval indices, and we were able to build choropleth maps of infestation levels <36 h after each round of trap inspection. Locating naturally infected vectors provides a timely support tool for local public health managers to prioritize areas for intervention response to prevent virus outbreaks.

Comprehensive assessment of germline pathogenic variant detection in tumor-only sequencing.

BACKGROUND: Tumor-only sequencing, implemented for the identification of somatic variants, is oftentimes used for the detection of actionable germline variants. We sought to determine whether tumor-only sequencing assays are suitable for detection of actionable germline variants, given their importance for the delivery of targeted therapies and risk-reducing measures. PATIENTS AND METHODS: The detection of germline variants affecting moderate- and high-penetrance cancer susceptibility genes (CSGs) by tumor-only sequencing was compared to clinical germline testing in 21 333 cancer patients who underwent tumor and germline testing using the Food and Drug Administration (FDA)-authorized Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Targets (MSK-IMPACT) assay. Seven homologous recombination deficiency (HRD), two DNA damage response (DDR) and four mismatch repair (MMR) genes, as well as NF1, RB1 and TP53 were included in the analysis. FDA-authorized and New York State Department of Health-approved sequencing methods for germline, tumor/normal and tumor-only sequencing assays and analytical pipelines were employed. RESULTS: In patients who underwent tumor and germline sequencing, as compared to clinical genetic testing, tumor-only sequencing failed to detect 10.5% of clinically actionable pathogenic germline variants in CSGs, including 18.8%, 12.8% and 7.3% of germline variants in MMR, DDR and HRD genes, respectively. The sensitivity for detection of pathogenic germline variants by tumor-only sequencing was 89.5%. Whilst the vast majority of pathogenic germline exonic single-nucleotide variants (SNVs) and small indels were detected by tumor-only sequencing, large percentages of germline copy number variants, intronic variants and repetitive element insertions were not detected. CONCLUSIONS: Tumor-only sequencing is adequate for the detection of clinically actionable germline variants, particularly for SNVs and small indels; however, a small subset of alterations affecting HRD, DDR and MMR genes may not be detected optimally. Therefore, for high-risk patients with negative tumor-only sequencing results, clinical genetic testing could be considered given the impact of these variants on therapy and genetic counseling.

Analysis of mutation status and homologous recombination deficiency in tumors of patients with germline BRCA1 or BRCA2 mutations and metastatic breast cancer: OlympiAD.

BACKGROUND: Presence of a germline BRCA1 and/or BRCA2 mutation (gBRCAm) may sensitize tumors to poly(ADP-ribose) polymerase (PARP) inhibition via inactivation of the second allele, resulting in gene-specific loss of heterozygosity (gsLOH) and homologous recombination deficiency (HRD). Here we explore whether tissue sample testing provides an additional route to germline testing to inform treatment selection for PARP inhibition. PATIENTS AND METHODS: In this prespecified exploratory analysis, BRCA1 and/or BRCA2 mutations in blood samples (gBRCAm) and tumor tissue (tBRCAm) were analyzed from patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer and known gBRCAm, enrolled in the phase III OlympiAD trial. The frequency and nature of tBRCAm, HRD score status [HRD-positive (score ≥42) versus HRD-negative (score <42) using the Myriad myChoice® CDx test] and rates of gsLOH were determined, and their impact on clinical efficacy (objective response rate and progression-free survival) was explored. RESULTS: Tissue samples from 161/302 patients yielded tBRCAm, HRD and gsLOH data for 143 (47%), 129 (43%) and 125 (41%) patients, respectively. Concordance between gBRCAm and tBRCAm was 99%. gsLOH was observed in 118/125 (94%) patients [BRCA1m, 73/76 (96%); BRCA2m, 45/49 (92%)]. A second mutation event was recorded for two of the three BRCA1m patients without gsLOH. The incidence of HRD-negative was 16% (21/129) and was more common for BRCA2m (versus BRCA1m) and/or for hormone receptor-positive (versus triple-negative) disease. Olaparib antitumor activity was observed irrespective of HRD score. CONCLUSIONS: gBRCAm identified in patients with HER2-negative metastatic breast cancer by germline testing in blood was also identified by tumor tissue testing. gsLOH was common, indicating a high rate of biallelic inactivation in metastatic breast cancer. Olaparib activity was seen regardless of gsLOH status or HRD score. Thus, additional tumor testing to inform PARP inhibitor treatment selection may not be supported for these patients.

'Candidatus Mycoplasma haematonasua' and tick-borne pathogens in ring-tailed coatis (Nasua nasua Linnaeus, 1976) from the Iguaçu National Park, Paraná State, southern Brazil.

The Iguaçu National Park (INP) is the largest remnant of Atlantic Forest in southern Brazil, representing an ecological continuum with Argentina. The INP harbours a diverse fauna, with ring-tailed coatis (Nasua nasua Linnaeus, 1976, Carnivora: Procyonidae) in close contact with tourists either begging and/or snatching food from visitors. A potentially novel haemotropic Mycoplasma sp. has been previously detected in the ring-tailed coatis from central-western and southern Brazil. Therefore, the aims of this study were to investigate the occurrence of haemotropic Mycoplasma sp. and tick-borne pathogens in wild ring-tailed coatis from the INP, Foz do Iguaçu municipality, Paraná State, southern Brazil. Blood samples were collected from 18 wild ring-tailed coatis and evaluated by conventional PCR (cPCR) assays for haemotropic Mycoplasma spp. (16S and 23S rRNA), Theileria/Babesia spp. (18S rRNA) and Ehrlichia/Anaplasma spp. (16S rRNA, sodB, dsb and groEL). Eight out of 18 (44.44%; 95% CI: 24.56%-66.28%) animals were positive for haemotropic Mycoplasma spp. All ring-tailed coatis tested negative for Theileria/Babesia spp. and only one out of 18 (5.56%; 95% CI: 0.99%-25.76%) animals tested positive for Ehrlichia/Anaplasma spp. by the 16S rRNA cPCR. Unfortunately, multiple attempts to sequence the 16S rRNA gene of the Ehrlichia/Anaplasma-positive sample have failed. Phylogenetic and network analysis of the hemoplasma 16S and 23S rRNA gene fragments confirmed that animals were infected by a potentially novel haemotropic Mycoplasma sp. previously reported in ring-tailed coatis from Brazil. The name 'Candidatus Mycoplasma haematonasua' is proposed for this novel organism.

Sanitizer efficacy in reducing microbial load on commercially grown hydroponic lettuce.

BACKGROUND: Most hydroponic lettuce growers harvest and package their marketable-size lettuces with an intact root ball. With a high microbial load on the peat moss substrate, there is a risk of microbial transfer onto the edible portion during packaging and throughout the product's shelf life. Since the produce is believed to have no contact with the substrate, no sanitizer wash is performed before packaging and storage. RESULTS: Aerobic plate count (APC) results suggested that reduction in count was influenced by both sanitizer application and storage time. Peroxyacetic acid significantly reduced APC count on leaves, roots, and substrate, with a 1.8 log CFU g-1 initial reduction on the leaf. Fungi and APC levels increased with storage time, with the greatest APC increase in the roots. Leaves had the lowest coliform bacteria (CB), with chlorine slightly reducing CB count. Unlike APC, CB levels decreased during storage on the substrate and root samples. No Listeria positive was confirmed by agglutination test. Further evaluation of different commercial substrates reveals that Com4, a drier-compacted plug, had the least ability to support growth/survival of all microbial populations enumerated relative to the spongy, wet black plugs. CONCLUSION: The ability of peat moss substrates to host microorganisms is influenced by the physical properties of the product. Sanitizer wash efficacy is dependent on the initial microbial load and the length of storage. Chlorine and peroxyacetic acid are effective in reducing microbial populations on the leaves of hydroponically grown lettuce without affecting visual quality during shelf life. © 2020 Society of Chemical Industry.

Defining clinical decision making in the provision of audio-visual outpatient care for acute upper limb trauma services: A review of practice.

The Covid-19 pandemic has accelerated the widespread adoption of technology-enabled care in the NHS.1 Moving into phase two of the response, the continuing use of audio-visual technology is expected, where appropriate, to be integral in the provision of safe, quality patient care.2 A clinical need therefore exists to identify when care can be safely delivered remotely using audio-visual technology and when there is a need for in-person contact.  At Salisbury Foundation Trust (SFT), during phase one of the NHS response to Covid-19, the decision to treat upper limb trauma patients in-person or remotely was made using clinical screening criteria. For many patients, audio-visual appointments offered a practical, time efficient way of accessing their reconstructive team for assessment, advice and post-operative care. However, a subset of patients was identified by the team as requiring at least one in-person consultation to minimize perceived clinical risk and to optimize quality outcomes.  In order to understand more fully the challenges and successes of technology-enabled care to date, a national survey of practice across hand units in the UK was conducted. We present here some of our key findings and propose the need to develop nationally agreed screening criteria to determine how and when technology enabled outpatient care can be used in the management of acute upper limb trauma. The results of this survey forms part of a series of projects currently underway looking at the efficacy of audio-visual care in upper limb trauma, including a multicentre observational study.

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.

Anaesthetic management of emergency caesarean section with isolated cortical vein thrombosis and subacute intracerebral haemorrhage.

We report the case of an emergency caesarean section 5 days following the onset of a right-sided hemiparesis due to an intracerebral haemorrhage. Computerised tomography imaging in the postoperative period revealed an isolated cortical vein thrombosis as the likely cause. The caesarean section was conducted under general anaesthesia following consideration of the risks and benefits and discussion of these with the patient. No peri-operative complications occurred and neuro-rehabilitation was commenced as an inpatient. This case highlights the importance of maintaining a targeted systolic blood pressure whilst avoiding increased intracranial pressure in the obstetric patient with an intracerebral haemorrhage, and that the mode and conduct of anaesthesia can have a profound impact on these measurements. To our knowledge, this is the first reported case of a patient having an emergency caesarean section after subacute intracerebral haemorrhage caused by an isolated cortical vein thrombosis and it demonstrates that general anaesthesia can be used safely in this context. In this complex obstetric case, the role of multidisciplinary team collaboration in the peri-operative period was essential to optimising the patient's outcome.

Accuracy of High-resolution Small-volume Cone-Beam Computed Tomography in the Diagnosis of Vertical Root Fracture: An In Vivo Analysis.

INTRODUCTION: The purpose of this in vivo study was to evaluate the accuracy of small-volume cone-beam computed tomographic (CBCT) imaging compared with conventional periapical radiography (CPR) in the diagnosis of vertical root fractures (VRFs) using exploratory surgery as the reference standard. METHODS: Eighty-two dental records of 85 teeth with suspected VRFs that underwent CPR, CBCT imaging, and exploratory surgery were included. Two observers assessed CPR and CBCT images independently for the presence or absence of root fractures, and findings from the exploratory surgery were considered the reference standard. Diagnostic sensitivity, specificity, accuracy, and the receiver operating characteristic curve values were obtained. The effect of single- and multirooted teeth on diagnostic accuracy as well as the association between clinical symptoms and the presence of VRFs were also assessed. RESULTS: VRFs were surgically detected in 64 of the 85 teeth (75.3%), of which 62.5% were multirooted and 76.6% had intracanal posts. CBCT imaging was more sensitive and accurate (65.6% and 64%) than CPR (27.3% and 40.5%). Both CPR and CBCT diagnostic accuracies were higher in single- than multirooted teeth. Pain on percussion, a localized periodontal pocket, and tooth mobility were associated with the presence of VRFs (P < .05; odds ratio = 4.15, 13.5 and 4.1, respectively). CONCLUSIONS: The accuracy of CBCT imaging for the diagnosis of VRFs was poor, although it was higher than with CPR. Multirooted teeth in the presence of intracanal posts may limit its diagnostic value.