Recurrent respiratory papillomatosis in northern Sweden: Clinical characteristics and practical guidance

Conclusion: Recurrent respiratory papillomatosis (RRP) patients with high surgical treatment frequency (≥ 1/year, HF) were significantly younger and had a more widespread laryngeal disease compared to a low frequency treated group (< 1 treatment/year, LF). This study confirms the existence of a clinical RRP group, not primarily related to HPV sub-type, but more care-intensive and in need of more vigilant follow-up. Objectives: RRP is associated with high morbidity due to its influence on breathing and voice. The purpose of this study was to characterize RRP patients in northern Sweden and investigate possible predictor factors affecting therapeutic needs. Method: Patients from the regional referral area (northern Sweden) were categorized for age, disease duration, juvenile or adult onset, profile of disease development, number of surgical sessions in relation to disease duration, laryngeal deposition of papilloma, gender, and HPV sub-types, in order to identify patients with increased need for frequent surgical treatment. Results: The median age of the RRP patients (n = 48) was 44.5 years; 34 (71%) were males and 14 (29%) females, most were infected with HPV 6. Patients with high surgical treatment frequency/year were significantly younger and showed more widespread papillomatous vegetation in the larynx, compared to the low frequency treated group.     

Advantages of an Anterior-Based Muscle-Sparing Approach in Transitioning From a Posterior Approach for Total Hip Arthroplasty: Minimizing the Learning Curve

BackgroundEnthusiasm for anterior-based approaches for total hip arthroplasty (THA) continues to increase but there is concern for increased complications during the learning curve period associated. This study aimed to investigate if there was a difference in perioperative variables, intraoperative and immediate postoperative complications, or patient-reported outcomes when transitioning from a mini-posterior approach (mPA) to an anterior-based muscle-sparing (ABMS) approach for THA.MethodsRetrospective cohort study on the first 100 primary THA cases (n = 96 patients) of the senior author (August 2016 to August 2017) using the ABMS approach. These cases were compared to primary THA cases done the year prior (July 2015 to July 2016, n = 91 cases in 89 patients) using an mPA. Data were extracted and analyzed via gamma regression with robust standard errors and using generalized estimating equation regression.ResultsWe found no difference in the estimated blood loss (P = .452) and surgical time (P = .564) between the cohorts. The ABMS cases had a slightly shorter length of stay (P = .001) with an adjusted mean length of stay of 1.53 days (95% confidence interval 1.4-1.6) compared to 1.85 days (95% confidence interval 1.8-1.9) in the mPA cases. There was no difference in the frequency of immediate postoperative complications (all, P > .05). There was no difference in the adjusted mean change in patient-reported outcomes (all P > .05). In the ABMS group, there was no difference in surgical time or physical function computerized adaptive test between the first 20 cases (reference) and each subsequent group of 20 cases (all P > .05).ConclusionThis study demonstrates no associated learning curve for an experienced senior surgeon when switching routine THA approach from mPA to ABMS. We advise careful interpretation of our results, as they may not apply to all surgeons and practices.Level of EvidenceLevel III Therapeutic Study: retrospective comparative study.     

美国胃肠病协会关于急性胰腺炎胰腺坏死处理临床实践专家共识更新解读

美国胃肠病协会（AGA）于2019年8月在Gastroenterology（《胃肠病学》）杂志上发表了针对胰腺坏死处理的临床实践专家共识的更新，归纳并总结了当前的临床证据与专家意见，旨在为胰腺坏死这一复杂临床情况的最佳干预提供指导建议。近年来，随着临床实践的不断深入，急性胰腺炎胰腺坏死的处理经历了较大的变革。从一开始的以手术为主的清创策略过渡到现阶段较为成熟的升阶梯治疗模式。针对胰腺坏死的治疗主要包含两个方面：非手术治疗和有创干预。其中，非手术治疗主要包括抗菌治疗和营养支持等。一旦坏死组织发生感染或无菌性坏死使病人产生显著临床症状，提示有强烈干预指征时，此时更多地依赖于有创干预。升阶梯治疗模式的主要内容为：以经皮引流或透壁内镜引流为首要手段，对于引流无法处理的大量固体坏死，可进行经皮微创或经内镜下坏死清除，若微创手段干预无效可进行开放手术清创。关于选择经皮微创阶梯治疗还是经内镜阶梯治疗，目前尚无研究显示两者之间对病死率等主要临床结局产生影响，不同治疗中心可根据各中心的专业特长和医疗资源，合理选择治疗方案。     

Method development of immunoglobulin G purification from micro-volumes of human serum for untargeted and targeted proteomics-based antibody repertoire studies

Immunoglobulins (Igs) are major serum proteins which play important roles in immunity. Both untargeted and targeted proteomic workflows can be applied to investigate antigen-binding sites and the glycosylation profiles of Igs. For a more-comprehensive picture of IgG from human serum, we developed an IgG purification process and coupled the standardized method to untargeted and targeted proteomic workflows for IgG investigations. Parameters such as the type of purification beads, volume of the bead slurry, incubation conditions, and binding capacities were evaluated in this study. Only 2 μL of human serum was required for each sample. The performance of coupling the purification process to untargeted proteomics in the IgG analysis was evaluated by comparing normalized abundances of IgG subclass-specific peptides with quantification results from an ELISA. Pearson's correlation values were all >0.82. Targeted proteomic workflow was applied to serum samples from patients with autoimmune pancreatitis and from healthy controls, and the results corresponded to clinical findings that IgG4-related peptides/glycopeptides showed higher abundances in the diseased group. The developed IgG purification process is simple and requires small sample volume, and it can be coupled to targeted and untargeted proteomic workflows for clinical investigations in the future.     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

Éthique de la recherche : réglementations françaises et applications en oncologie radiothérapie

French regulations about research ethics are based on the so-called Jardé law, which defines researches involving human beings. Researches involving human beings require the submission of research protocols to a committee for protection of persons with a precise list of documents to submit for a favourable opinion. This law describes different categories of researches and determines the ethical procedures to apply before setting up a research protocol. This issue of categorisation is central and must be taken into account by researchers from the beginning of the research process. Researches considered as not involving human beings also require a set of ethical precautions focused on patients’ information and the collection of their non-opposition (due to the application of the General Data Protection Regulation adopted by the European Parliament). Thus, many regulations exist and they require a real work for researchers to meet these requirements in research ethics. This article aims to summarise French regulations. Selected examples are specifically taken into the field of radiation oncology research.     

Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.     

How current risk assessment and risk management methods for drinking water in The Netherlands cover the WHO water safety plan approach

In the Netherlands, safe and sufficient drinking water is provided to the general population by ten drinking water companies. To guarantee safe drinking water the World Health Organization (WHO) developed a Water Safety Plan (WSP), a Risk Assessment and a Risk Management (RA/RM) framework. The objective of the study was to identify legally required RA approaches, to document application of RA/RM activities at Dutch drinking water companies and to determine to what extent these RA/RM activities as a whole cover all the elements of the WHO WSP approach. This study could be of interest to both managers of large water utilities and decision makers.The assessment was performed by means of a policy review and interviews with two to four staff members involved in RA/RM from all ten Dutch drinking water companies combined with a joint workshop. The drinking water companies are well aware of the potential hazards and risks that can influence the drinking water quality. To guarantee the supply of safe and sufficient drinking water, the Dutch drinking water sector uses six different legally required RA/RM approaches. This study shows that by using the six legally required RA/RM approaches, all WSP steps are covered. WSP entails a generic risk assessment for identifying all hazards and hazardous events from source to tap, whereas the six legally required RA/RM each focus on specific risks at an advanced level. Each risk assessment provides information on specific hazards and hazardous events covering a part of the water supply chain. These legal requirements are complemented with additional RA/RM activities at sector and water company level such as codes of practices and standard operating procedures. The outcomes of all RA/RM approaches combined provide information from source to tap. When using multiple RA/RM approaches, it is crucial to share and combine information derived from the different activities.