Diagnosis and management of phyllodes tumours for the surgeon: An algorithm

A Phyllodes Tumour (PT) is an uncommon fibroepithelial lesion, with three histological grades – benign, borderline and malignant. PTs cause significant challenges in diagnosis, management and prognostication. Recent publications have clarified the definitions and prognostication of PTs. Contemporary data currently challenge international guidelines on PT management. We performed an in-depth literature review to develop a best-practice management algorithm for PTs.Diagnostic recommendations are that neither current imaging techniques, nor fine-needle biopsies, can reliably diagnose a PT. Core needle biopsy is the optimal diagnostic technique. Indeterminate or suspicious lesions are recommended to undergo an excisional biopsy due to the inherently heterogeneous nature of PTs.Management guidelines are that benign PTs should be completely excised, although an involved margin is acceptable in select situations. Borderline PTs should have a clear margin on excision due to their higher risk of recurrence, as well as the potential for a recurrence to progress to a malignant PT. In malignant PTs, a margin of 3 mm is acceptable as there is no reduction in recurrence risk if margins are >3 mm. Routine axillary surgery is not indicated in PTs, with axillary surgery only indicated in a histologically-confirmed positive axilla.Adjuvant treatment recommendations are that borderline and malignant PTs should be discussed at MDT, with radiotherapy considered in both. Chemotherapy should be discussed in malignant PT patients.In summary, we have developed an up-to-date simple algorithm to guide the surgeon's management of patients diagnosed with PTs and reduce excessive surgery.     

ICD-10 anaphylaxis algorithm and the estimate of vaccine-attributable anaphylaxis incidence in Medicare

BackgroundAnaphylaxis is a rare, serious allergic reaction. Its identification in large healthcare databases can help better characterize this risk.ObjectiveTo create an ICD-10 anaphylaxis algorithm, estimate its positive predictive values (PPVs) in a post-vaccination risk window, and estimate vaccination-attributable anaphylaxis rates in the Medicare Fee For Service (FFS) population.MethodsAn anaphylaxis algorithm with core and extended portions was constructed analyzing ICD-10 anaphylaxis claims data in Medicare FFS from 2015 to 2017. Cases of post-vaccination anaphylaxis among Medicare FFS beneficiaries were then identified from October 1, 2015 to February 28, 2019 utilizing vaccine relevant anaphylaxis ICD-10 codes. Information from medical records was used to determine true anaphylaxis cases based on the Brighton Collaboration’s anaphylaxis case definition. PPVs were estimated for incident anaphylaxis and the subset of vaccine-attributable anaphylaxis within a 2-day post-vaccination risk window. Vaccine-attributable anaphylaxis rates in Medicare FFS were also estimated.ResultsThe study recorded 66,572,128 vaccinations among 21,685,119 unique Medicare FFS beneficiaries. The algorithm identified a total of 190 suspected anaphylaxis cases within the 2-day post-vaccination window; of these 117 (62%) satisfied the core algorithm, and 73 (38%) additional cases satisfied the extended algorithm. The core algorithm’s PPV was 66% (95% CI [56%, 76%]) for identifying incident anaphylaxis and 44% (95% CI [34%, 56%]) for vaccine-attributable anaphylaxis. The vaccine-attributable anaphylaxis incidence rate after any vaccination was 0.88 per million doses (95% CI [0.67, 1.16]).ConclusionThe ICD-10 claims algorithm for anaphylaxis allows the assessment of anaphylaxis risk in real-world data. The algorithm revealed vaccine-attributable anaphylaxis is rare among vaccinated Medicare FFS beneficiaries.     

独立成分分析及其应用的研究进展

独立成分分析(ICA)是一项把混合信号分解成具有统计独立性成分的新技术。ICA近年已在生物医学和雷达等领域的信号分离中展示了很好的应用前景。我们比较系统地介绍了ICA的基本原理、主要算法、应用和将来ICA研究的发展方向，旨在进一步推动有关的理论与应用研究工作。     

卵巢癌风险预测模型在上皮性卵巢癌早期诊断中的应用价值

目的：探讨卵巢癌风险预测模型（ROMA）对上皮性卵巢癌患病风险的评估价值及与患者临床病理分期的关联性,为上皮性卵巢癌的临床诊疗及预后分析提供依据。方法：回顾性分析经术后石蜡切片病理确诊的135例卵巢肿瘤患者的临床资料,将其分为卵巢良性肿瘤组（n=66）、上皮性卵巢癌组（n=58）和非上皮性卵巢癌组（n=11）。根据各组患者术前检测的血清人附睾蛋白4（HE4）和糖类抗原125（CA125）水平计算其ROMA值,根据各组患者HE4、CA125和ROMA临界值计算HE4、CA125和ROMA阳性率,分析卵巢癌患者血清HE4、CA125和ROMA阳性率与患者临床分期之间的关系,评价其对卵巢肿瘤患者的诊断效能。结果：上皮性卵巢癌组患者血清HE4、CA125水平和ROMA值均明显高于卵巢良性肿瘤组及非上皮性卵巢癌组（P<0.05）。上皮性卵巢癌组患者HE4、CA125和ROMA阳性率均高于卵巢良性肿瘤组（P<0.01）,并随着临床分期的升高而升高。与HE4和CA125阳性率比较,卵巢良性肿瘤患者ROMA阳性率最低,在各期上皮性卵巢癌中ROMA阳性率均高于CA125阳性率。ROMA在绝经后卵巢肿瘤患者组的敏感度及阴性预测值均高于绝经前卵巢肿瘤患者组（P<0.05）,而特异度及阳性预测值在绝经前及绝经后卵巢肿瘤患者组间比较差异无统计学意义（P>0.05）。3项指标中,ROMA的各项诊断效能指标最高,CA125的各项诊断效能指标最低。结论：ROMA对上皮性卵巢癌风险的诊断价值高于CA125或HE4,对绝经后患者具有更好的诊断价值,可提高卵巢癌的早期诊断效能。     

An algorithm for choosing among smoking cessation treatments

Currently, there are nine validated medications, four validated psychosocial strategies, and three validated ways to deliver psychosocial treatments for smoking cessation. This article presents an algorithm based on a literature review and the author's clinical experience. The algorithm integrates the recommendations of the major guidelines and meta-analyses and provides rationales for its treatment decisions. The algorithm suggests a brief assessment followed by use of one to two medications and counseling in most smokers. Because all treatments appear equally effective and have few adverse events, the algorithm suggests clinicians inform smokers of the pros and cons of the different treatments, and recommend use of one or more of each. If a smoker fails to quit, the algorithm suggests an assessment of why relapse occurred and then a more intense treatment, a new treatment, or both.     

pH adjustment of human blood plasma prior to bioanalytical sample preparation

pH adjustment in bioanalytical sample preparation concerning ionisable compounds is one of the most common sample treatments. This is often done by mixing an aliquot of the sample with a proper buffer adjusted to the proposed pH. The pH of the resulting mixture however, does not necessarily have to be the same as the pH of the used buffer due to the significant buffer capacity of the sample. Calculation methods from titration technology were adapted and applied to this problem. The acid-base characteristics of human blood plasma and serum samples were determined and used to calculate the pH of buffer-plasma mixtures. Based on these parameters and the characteristics of the used buffers, two alternative methods were described to prepare buffers that lead to the proposed pH when mixed in the right volume ratio with human plasma samples. The resulting pH of several mixtures of different buffers with human blood plasma were in good accordance with the calculated pH. The proposed calculation methods and recommended buffer preparation methods may lead to more robust bioanalytical methods.     

Mapping and definition of HLA class I and II serologic epitopes using an unbiased reverse engineering strategy

Current models describing HLA epitopes are both theoretical and empirical. Each has limitations yielding discordant results and increasingly complex modeling. The models make a priori assumptions that epitopes must be present only on the mature protein, solvent accessible, on the ‘top’ (peptide binding surface) of the molecule, restricted to the same class as the antibody, and in the same position on the target allele if reactive to more than one locus. Results obtained counter to these assumptions are routinely discounted. For the 17th International Histocompatibility and Immunogenetics Workshop, we developed a reverse engineering algorithm to define epitopes without these assumptions on a cohort of 332 primary transplant pairs. Complete NGS typing of the transcribed (including leader) genomic DNA for 11 HLA loci of donor and recipient and DSA assignment by single antigen beads was performed. Our results show that, when grouped by 16 class I and II allele specific DSA, uniform clusters and 172 specific amino acid target epitopes are recognized by recipients despite originating from disparate HLA pairs. Data also show that these targets can be in the leader, alpha 3, transmembrane and cytoplasmic domains, thus calling into question current assumptions regarding immunogenic epitopes. Comparisons of amino acid epitopes defined by the Terasaki and Duquesnoy groups (TerEp and EpRegistry) are given.     

Automatic initial contact detection during overground walking for clinical use

The division of gait into cycles is crucial for identifying deficits in locomotion, particularly to monitor disease progression or rehabilitative recovery. Initial contact (IC) events are often used to separate movement into repetitive cycles yet automatic methods for IC identification in pathological gait are limited in both number and capacity. The aim of this work was to develop a more precise algorithm in IC detection. A projected heel markers distance (PHMD) algorithm is presented here and compared for accuracy to the high pass algorithm (HPA) in IC identification. Kinematic gait data from two clinical cohorts were analyzed and processed automatically for IC detection: (1) unilateral total hip arthroplasty (THA) patients (n = 27) and (2) cerebral palsy pediatric (CPP) patients (n = 20). IC events determined by the two algorithms were benchmarked against the IC events detected manually and from force plates. The PHMD method detected 96.6% IC events in THA patients and 99.1% in CPP patients with an average error of 5.3 ms and 18.4 ms. The HPA method detected 99.1% IC events in THA patients and 97.3% IC events in CPP patients, with an average error of 57.5 ms and 10.2 ms. PHMD identified no superfluous IC events, whereas 51.5% of all THA IC and 47.6% of CPP IC were superfluous events requiring manual deletion with HPA. With the superior comparison against the current gold standard, the PHMD algorithm appears valid for a wide spectrum of clinical data sets and allows for precise, fully automatic processing of kinematic gait data without additional sensors, triggers, or force plates.