Epithelial ovarian cancer risk: A review of the current genetic landscape

Ovarian cancer is the fourth most common cause of cancer-related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk-reduction strategies. Germline pathogenic variants in EOC susceptibility genes including those involved in homologous recombination and mismatch repair pathways are present in approximately 22% to 25% of EOC. These genes are associated with an estimated lifetime risk of EOC of 13% to 60% for BRCA1 variants and 10% to 25% for BRCA2 variants, with lower risks associated with remaining genes. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) thought to explain an additional 6.4% of the familial risk of ovarian cancer, with 34 susceptibility loci identified to date. However, an unknown proportion of the genetic component of EOC risk remains unexplained. This review comprises an overview of individual genes and SNPs suspected to contribute to risk of EOC, and discusses use of a polygenic risk score to predict individual cancer risk more accurately.     

Paresthesia‐Free Spinal Nerve Root Stimulation for the Treatment of Chronic Neuropathic Pain

ObjectiveStimulation of the dorsal spinal roots, or spinal nerve root stimulation (SNRS), is a neuromodulation modality that can target pain within specific dermatomal distributions. The use of paresthesia-free stimulation has been described with conventional dorsal column spinal cord stimulation, although has yet to be described for SNRS. This objective of this study was to investigate the efficacy of paresthesia-free high-frequency (1000–1200 Hz) SNRS in the treatment of intractable, dermatomal neuropathic pain.Materials and MethodsA retrospective chart review was performed on 14 patients implanted with SNRS in varying distributions: Ten patients initially received tonic stimulation and crossed over to a paresthesia-free paradigm and four patients received only paresthesia-free stimulation. The primary outcome was reduction in pain severity (visual analog scale [VAS]), measured at baseline and follow-up to 24 months with paresthesia-free stimulation.ResultsAll 14 patients who received paresthesia-free stimulation had significant improvement in pain severity at a mean follow-up of 1.39 ± 0.15 years (VAS 7.46 at baseline vs. 3.25 at most recent follow-up, p < 0.001). Ten patients were initially treated with tonic stimulation and crossed over to paresthesia-free stimulation after a mean of 61.7 months. Baseline pain in these crossover patients was significantly improved at last follow-up with tonic stimulation (VAS 7.65 at baseline vs. 2.83 at 48 months, p < 0.001), although all patients developed uncomfortable paresthesias. There was no significant difference in pain severity between patients receiving tonic and paresthesia-free stimulation.ConclusionsWe present real-world outcomes of patients with intractable dermatomal neuropathic pain treated with paresthesia-free, high-frequency SNRS. We demonstrate its effectiveness in providing pain reduction at a level comparable to tonic SNRS up to 24 months follow-up, without producing uncomfortable paresthesias.     

Dynamic Indicators That Impact the Outcomes of Thoracic Endovascular Aortic Repair in Complicated Type B Aortic Dissection

PurposeTo investigate dynamic variables obtained from retrospective computed tomography angiography for ability to predict thoracic endovascular aortic repair (TEVAR) outcomes in patients with complicated type B aortic dissection (cTBAD).Materials and MethodsSeventy-nine patients with cTBAD who received TEVAR from March 2009 to June 2018 were retrospectively enrolled. Relative true lumen area (r-TLA) was computed at the level of tracheal bifurcation every 5% of all R-R intervals. Parameters that reflect the state of intimal motion were evaluated, including difference between maximum and minimum r-TLA (D-TLA) and true lumen collapse. The endpoints comprised early (≤ 30 days) and late (> 30 days) outcomes after intervention.ResultsOverall early mortality rate was 13.9% (11/79), and early adverse events rate was 24.1% (19/79). Patients who received TEVAR within 2 days of symptom onset demonstrated the worst outcomes. A longer time of r-TLA < 25% in 1 cardiac cycle (P = .049) and larger D-TLA (P < .001) were correlated to an increased early death. In addition, D-TLA was an independent predictor of early mortality. Area under the curve of D-TLA was 0.849 (95% confidence interval 0.730–0.967) for predicting early mortality and 0.742 (95% CI 0.611–0.873) for predicting early adverse events. Survival and event-free survival rates during follow-up were decreased in the D-TLA > 21.5% group compared with the D-TLA ≤ 21.5% group (all P < .001).ConclusionsLarger D-TLA is correlated with worse postoperative outcomes and might be a crucial parameter for future risk stratification in patients with cTBAD.     

Novel design of miniplate for fixation of fractures at transition zone of parasymphysis-body region of mandible – A clinical randomised study

Fractures through the mandible at the level of the parasymphysis extending obliquely and traversing through the transitional zone to body region are relatively common. Therefore, a surgeon should have an appropriate understanding of the biomechanics of different plating techniques to fix these fractures. There is always a dilemma for the surgeon as to whether to fix these mandibular segments with one or two miniplates, and the presence of mental neurovascular bundle makes it more challenging. A study was planned in the Department of Oral and Maxillofacial Surgery to evaluate a novel twin-fork design of a miniplate used for fracture fixation at the transition zone of parasymphysis and body region of mandible after an in-vitro study of same design, and provided encouraging results. A total of 30 patients (10 patients in three groups each) were included in the study. All patients were evaluated preoperatively and postoperatively for operating time, ease of placement of miniplate, occlusion, reduction of fracture, neurosensory disturbances and infection. The novel design of twin-fork−shaped miniplate proved to be superior to the conventional miniplate in terms of neurosensory (Fisher exact test 17.40; p = 0.003) and functional outcome. There was statistically significant difference (χ² = 13.895, p = 0.031) in postoperative reduction of fracture at week 4, indicating superiority of the twin-fork miniplate among the other conventional designs. The study concludes that the use of newly designed twin-fork−shaped miniplate should be encouraged in the fractures of transitional zone of parasymphysis-body region involving mental neurovascular bundle.     

Advance in Functional Restoration of Injured Nerve with Low Level Laser and its Utilization in the Dental and Maxillofacial Region

The inferior alveolar nerve and facial nerve are the two most important nerves in the dental and maxillofacial region. The injury to them is one of the major postoperative complications after alveolar surgery and orthognathic surgery. However, recovering the nerve function after injury takes a long time and the recovery effect tends to be unsatisfactory. In recent years, an intensively investigated technique, low level laser which has been applying in assisting the recovery of nerve function, has been gradually proved to be effective in clinically treating postoperative nerve injury. In this article we review in terms of the mechanisms involved in low level laser-assisted functional restoration of nerve injury and its clinical application in the recovery of nerve function in the dental and maxillofacial area as well.     

抗PD-(L)1、抗CTLA-4免疫治疗标志物研究进展

免疫检查点抑制剂已经改变了包括肺癌、黑色素瘤等许多肿瘤的治疗情况，并且在一些难治性肿瘤中表现出持久的应答率，然而在部分接受治疗的患者中表现出无反应及严重免疫相关副作用。为了优化免疫疗法的使用，可能需要多种临床应答的预测性标志物。本研究回顾了几种潜在有效生物标志物的可用数据，通过免疫组化检测肿瘤细胞和免疫细胞中PD-L1的表达，提示其是一种临床疗效的良好预测标志物;且PD-L1表达阴性者经免疫治疗后仍可获益。PD-L1表达在肿瘤内是动态和异质性的:在原发性灶和转移灶之间或在穿刺标本和大体标本之间表达不一致。肿瘤突变负荷与新抗原的高比率可获得持久获益。外周血标志物也可作为潜在标志物，增加的绝对淋巴细胞计数（ALC）与疾病控制和生存显著相关。在这篇综述中，我们旨在讨论抗PD-（L）1与抗CTLA-4 免疫治疗相关标志物研究现状，为临床运用提供指导，以便能够准确筛选出从这些治疗中获益更多的患者。     

“Cheese Wire” Fenestration of Dissection Intimal Flap to Facilitate Thoracic Endovascular Aortic Repair in Chronic Dissection

Thoracic endovascular aortic repair (TEVAR) for aneurysmal chronic dissection is often complicated by retrograde filling of the false lumen and dissected distal landing zone. A “cheese wire”-style fenestration of the dissection intimal flap can create a landing zone facilitating TEVAR. This technique successfully aided TEVAR in 3 patients with an average age of 57.3 years. Complications included type III endoleak requiring relining and renal artery occlusion requiring stent placement. Average duration of clinical follow-up was 19 ± 4 months. Imaging follow-up was 8 ± 10 months. All patients have survived for more than 1 year without aneurysm enlargement.