Artificial intelligence and machine learning for hemorrhagic trauma care

Artificial intelligence(AI),a branch of machine learning(ML)has been increasingly employed in the research of trauma in various aspects.Hemorrhage is the most common cause of trauma-related death.To better elucidate the current role of AI and contribute to future development of ML in trauma care,we conducted a review focused on the use of ML in the diagnosis or treatment strategy of traumatic hemorrhage.A literature search was carried out on PubMed and Google scholar.Titles and abstracts were screened and,if deemed appropriate,the full articles were reviewed.We included 89 studies in the review.These studies could be grouped into five areas:(1)prediction of outcomes;(2)risk assessment and injury severity for triage;(3)prediction of transfusions;(4)detection of hemorrhage;and(5)prediction of coagulopathy.Performance analysis of ML in comparison with current standards for trauma care showed that most studies demonstrated the benefits of ML models.However,most studies were retrospective,focused on prediction of mortality,and development of patient outcome scoring systems.Few studies performed model assessment via test datasets obtained from different sources.Prediction models for transfusions and coagulopathy have been developed,but none is in widespread use.AI-enabled ML-driven technology is becoming integral part of the whole course of trauma care.Comparison and application of ML algorithms using different datasets from initial training,testing and validation in prospective and randomized controlled trials are warranted for provision of decision support for individualized patient care as far forward as possible.

A comparison of financial and operational efficiency between smart and traditional insufflation for laparoscopic surgery: A granular analysis

Objective:Smart insufflation(SI)techniques relying on valve and membrane-free insufflation are increasing in usage.Although considerable literature exists demonstrating the benefits of SI on procedural ease and patient outcomes,there remains a paucity describing the financial impact of these devices.The purpose of this study was to determine the financial and efficiency impact of these devices on the operating room and inpatient wards of a hospital.Methods:A discrete event simulation model representing a typical mid-sized North American hospital comparing SI to traditional insufflation(TI)was generated.The National Surgical Quality Improvement database from 2015 to 2019 was used to populate the model with data supplemented from the literature.Outcomes included length of stay(LOS),duration of surgery(DOS),annual procedure volume,profit,return on investment(ROI),and gross profit margin(GPM).From the literature review,DOS savings were 10e32 minutes/case,while LOS savings were 0e3 days/case.Results:Implementation of an SI led to an increase in annual throughput of 42e346(4.4%e36.6%)cases for all procedures and 38 to 297(4.3%e33.3%)cases for complex procedures.LOS was found to be decreased by 175e614(18.3%e64.2%)days for all procedures and 231 to 614(35.6%e77.9%)cases for complex procedures with the implementation of an SI.Together,this resulted in an increase in net profit of$104,685 per annum.The ROI of SI over the TI device was>1000%,and the GPM for the TI was 90.0%,while the GPM for the SI was 71.7%.Conclusion:Despite the initial financial investment being greater,the implementation of SI offsets these expenses and yields significant financial benefits.Our study demonstrates the financial benefits of SI over TI and illustrates how granular operational and financial analyses of technologies are essential to aid in sound healthcare procurement decision making.

Inflammatory bowel disease and thromboembolism

Patients with inflammatory bowel disease(IBD) have an increased risk of vascular complications. Thromboembolic complications,both venous and arterial,are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to Thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown,but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature,as well as in the systemic circulation. Clinicians' awareness of the risks,and their ability to promptly diagnose and manage TEs are of vital importance. In this review we discuss how thromboembolic disease is related to IBD,specifically focusing on:(1) the epidemiology and clinical features of thromboembolic complications in IBD;(2) the pathophysiology of thrombosis in IBD;and(3) strategies for the prevention and management of thromboembolic complications in IBD patients.

Current role of minimally invasive approaches in the treatment of early gastric cancer

Despite declining incidence,gastric cancer remains one of the most common cancers worldwide.Early detection in population-based screening programs has increased the number of cases of early gastric cancer,representing approximately 50%of newly detected gastric cancer cases in Asian countries.Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis.Laparoscopic and robotic resections for early gastric cancer,including function-preserving resections,have propagated through advances in technology and surgeon experience.The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer.

MRI显示颈动脉中度狭窄斑块内出血预测无症状男性发生脑血管缺血事件危险度的研究

目的研究颈动脉中度狭窄无症状男性快速三维T1加权抑脂扰相梯度回波序列MRI显示颈动脉斑块内出血（IPH）与远期同侧脑血管事件间的关系。材料与方法此项回顾性研究经机构伦理委员会批准免除书面知情同意通知。所有病人在电话随访中都给予了口头知情同意通知。回顾性分析2003--2006年间在血管门诊就诊，发现无症状颈动脉狭“弥漫受累”）、血清参数和疾病分期，以及与伴或不伴皮质破坏之脊柱外病变检出可能性的相关性。

Pea3 expression promotes the invasive and metastatic potential of colorectal carcinoma

AIM:To investigate the function of Pea3 in colorectal carcinoma(CRC)invasion and metastatic potential.METHODS:The expression of Pea3 during clinical progression of human CRC was investigated using Oncomine Research Edition.To assay Pea3 expression in established CRC cell lines,we performed western blotting of cell lysates.We employed sh RNA-mediated knockdown of Pea3 in HCT116(HCT)and LS174T CRC cells which was confirmed by real-time quantitative PCR(q PCR)and western blotting.Transwell invasion assays,MTS proliferation assays,anoikis assays,and fluorometric matrix metalloprotease(MMP)assays wereperformed to determine the effects of Pea3 knockdown on invasion,proliferation,anoikis and MMP activity in CRC cells in vitro.Alterations in epithelial-mesenchymal transition(EMT)and matrix metalloprotease(MMP)m RNA levels were determined by q PCR.CRC cells were injected into the flanks of nude mice to generate xenografts and tumor growth monitored with serial calliper measurements.To assay metastatic potential,CRC cells were injected into the spleen of nude mice,and histological analysis performed on the livers 21 d later.RESULTS:We demonstrated that reduction of Pea3expression in CRC cells significantly impaired their invasive capacity(HCT.sh Pea3,0.28±0.04 fold,P<0.01;LS.sh Pea3,0.15±0.04 fold;SW.sh Pea3,0.23±0.03,P<0.01),reduced anoikis resistance(HCT.sh Pea3 75.4%±1.9%viable cells vs HCT.sh Ctrl 88.6%±0.6%viable cells,P<0.01;LS.sh Pea3 71.7%±0.5%viable cells vs LS.Ctrl 89.6%±0.3%viable cells,P<0.005,but had no effect on proliferation(HCT.sh Ctrl AUC 5098±123 vs HCT.sh Pea3 5689±151,P<0.05;LS.sh Ctrl AUC 5600±324.1 vs LS.sh Pea3 6423±400,P<0.05).In vivo,HCT.sh Pea3 and HCT.sh Ctrl tumour xenografts grew at a similar rate(HCT.sh Pea3 2.64±0.82 fold vs HCT.sh Ctrl 2.88±0.80 fold,P>0.05).In keeping with a pro-metastatic function for Pea3 in CRC,several EMT markers and MMPs were downregulated in sh Pea3-expressing cells,suggesting that Pea3 may exert its effects through these processes.A reduction in overall MMP activity was observed in HCT.sh Pea3 cells compared to their control counterparts(HCT.sh Pea30.61±0.04 fold,P<0.005).This translated in vivo to the complete absence of metastases in the livers of mice that were grafted with CRC cells lacking Pea3.Conversely,CRC cells expressing Pea3 formed liver metastases in all mice.CONCLUSION:Our study implicates Pea3 as a mediator of metastases,and provides a biological rationale for the adverse prognosis associated with elevated Pea3 expression in human CRC.

Inflammatory pouch disease: The spectrum of pouchitis

Restorative proctocolectomy with ileal-pouch anal anastomosis(IPAA) is the operation of choice for medically refractory ulcerative colitis(UC), for UC with dysplasia, and for familial adenomatous polyposis(FAP). IPAA can be a treatment option for selected patients with Crohn's colitis without perianal and/or small bowel disease. The term "pouchitis" refers to nonspecific inflammation of the pouch and is a common complication in patients with IPAA; it occurs more often in UC patients than in FAP patients. This suggests that the pathogenetic background of UC may contribute significantly to the development of pouchitis. The symptoms of pouchitis are many, and can include increased bowel frequency, urgency, tenesmus, incontinence, nocturnal seepage, rectal bleeding, abdominal cramps, and pelvic discomfort. The diagnosis of pouchitis is based on the presence of symptoms together with endoscopic and histological evidence of inflammation of the pouch. However, "pouchitis" is a general term representing a wide spectrum of diseases and conditions, which can emerge in the pouch. Based on the etiology we can sub-divide pouchitis into 2 groups: idiopathic and secondary. In idiopathic pouchitis the etiology and pathogenesis are still unclear, while in secondary pouchitis there is an association with a specific causative or pathogenetic factor. Secondary pouchitis can occur in up to 30% of cases and can be classified as infectious, ischemic, non-steroidal antiinflammatory drugs-induced, collagenous, autoimmuneassociated, or Crohn's disease. Sometimes, cuffitis or irritable pouch syndrome can be misdiagnosed as pouchitis. Furthermore, idiopathic pouchitis itself can be sub-classified into types based on the clinical pattern, presentation, and responsiveness to antibiotic treatment. Treatment differs among the various forms of pouchitis. Therefore, it is important to establish the correct diagnosis in order to select the appropriatetreatment and further management. In this editorial, we present the spectrum of pouchitis and the specific features related to the diagnosis and treatment of the various forms.

Contemporary approach to active surveillance for favorable risk prostate cancer

The approach to favorable risk prostate cancer known as“active surveillance”was first described explicitly in 2002.This was a report of 250 patients managed with a strategy of expectant management,with serial prostate-specific antigen and periodic biopsy,and radical intervention advised for patients who were re-classified as higher risk.This was initiated as a prospective clinical trial,complete with informed consent,beginning in 2007.Thus,there are now 20 years of experience with this approach,which has become widely adopted around the world.In this chapter,we will summarize the biological basis for active surveillance,review the experience to date of the Toronto and Hopkins groups which have reported 15-year outcomes,describe the current approach to active surveillance in patients with Gleason score 3þ3 or selected patients with Gleason score 3þ4 with a low percentage of Gleason pattern 4 who may also be candidates,enhanced by the use of magnetic resonance imaging,and forecast future directions.

Inpatient rehabilitation outcomes in solid organ transplantation: Results of a unique partnership between the rehabilitation hospital and the multi-organ transplant unit in an acute hospital

Objective: To determine the outcomes in solid organ transplant recipients following inpatient rehabilitation, as a result of a unique partnership between the rehabilitation hospital and the multi-organ transplant program in an acute hospital. Design: Retrospective observational study. Setting: Community rehabilitation hospital affiliated with a university. Participants: A cohort of 173 organ transplant patients admitted consecutively over a four-year period (2004-2008) was compared to a cohort of all rehabilitation patients (n = 9762) admitted to the same inpatient rehab facility during the same period. Interventions: Inpatient rehab program to all participants. Main Outcome Measures: Length of hospital stay, Functional Independence Measure (FIMTM) change (admission-discharge), and rate of discharges to home. Results: Outcomes were measured using components of the FIMTM instrument, admission and discharge data. Chi-square and independent two-sample t-tests were used for statistical analysis. Compared to a general rehabilitation inpatient population, transplant rehabilitation inpatients had: more immediate (TM change (8.9 vs. 20.9, p TM efficiency (1.1 vs. 1.4, p < 0.001);and a higher rate of discharges to home in patients not readmitted to acute care (98.5% vs. 94.5% p < 0.001). Conclusion: Outcomes of rehabilitation in solid organ transplant patients are comparable but not identical to those in other patient groups. Inpatient rehabilitation for transplant patients is therefore fully justifiable and necessary. The ten times higher rate of transplant patient readmission to acute hospital must be communicated, facilitated, accepted and managed within a partnership strategy.

Pulmonary fibrosis and emphysema: Is the emphysema type associated with the pattern of fibrosis?

AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography(HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema(CPFE).METHODS: Fifty-three smokers with upper lobe emphysema and lower lobe pulmonary fibrosis on- HRCT-were retrospectively evaluated. Patients were stratified into 3 groups according to the predominant type of emphysema: Centrilobular(CLE), paraseptal(PSE), CLE = PSE. Patients were also stratified into 3 other groups according to the predominant type of fibrosis on HRCT: Typical usual interstitial pneumonia(UIP), probable UIP and nonspecific interstitial pneumonia(NSIP). HRCTs were scored at 5 predetermined levels for the coarseness of fibrosis(Coarseness), extent of emphysema(emphysema), extent of interstitial lung disease(Tot Ext ILD), extent of reticular pattern not otherwise specified(Ret NOS), extent of ground glass opacity with traction bronchiectasis(extG GOBx), extent of pure ground glass opacity and extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion capacity(DLCO) and systolic pulmonary arterial pressure were compared among the groups.RESULTS: The predominant type of emphysema was strongly correlated with the predominant type of fibrosis. The centrilobular emphysema group exhibited a significantly higher extent of emphysema(P < 0.001) and a lower extent of interstitial lung disease(P < 0.002), reticular pattern not otherwise specified(P < 0.023), extent of ground glass opacity with traction bronchiectasis(P < 0.002), extent of honeycombing(P < 0.001) and coarseness of fibrosis(P < 0.001) than the paraseptal group. The NSIP group exhibited a significantly higher extent of emphysema(P < 0.05), total lung capacity(P < 0.01) and diffusion capacity(DLCO)(P < 0.05) than the typical UIP group. The typical UIP group exhibited a significantly higher extent of interstitial lung disease, extent of reticular pattern not otherwise specified, extent of ground glass opacity with traction bronchiectasis, extent of honeycombing and coarseness of fibrosis(0.039 > P > 0.000). Although the pulmonary arterial pressure was higher in typical UIP group relative to the NSIP group, the difference was not statistically significant.CONCLUSION: In CPFE patients, paraseptal emphysema is associated more with UIP-HRCT pattern and higher extent of fibrosis than centrilobular emphysema.

Strategies to tackle the challenges of external beam radiotherapy for liver tumors

Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies.

Liver involvement in the drug reaction,eosinophilia,and systemic symptoms syndrome

First described in 1996,the drug reaction,eosinophilia,and systemic symptoms syndrome(DReSS) is considered,along with Stevens-Johnson syndrome and toxic epidermal necrolysis,a severe cutaneous drug reaction. It is characterized by the presence of a maculopapular erythematous skin eruption,fever,lymphadenopathy,influenza-like symptoms,eosinophilia,and visceral involvement such as hepatitis,pneumonitis,myocarditis,pericarditis,nephritis,and colitis. The prognosis of patients with DReSS is related to the severity of visceral involvement. The mortality ranges from approximately 5% to 10%,and death is mainly due to liver failure,which is also the organ most commonly involved in this syndrome. Although it was previously hypothesized in 1994,DReSS syndrome can lead to reactivation of one or more human herpesvirus family members. Now being included as diagnostic criteria in a proposed diagnostic score system,this reactivation can be detected up to 2-3 wk after DReSS syndrome onset. Other causes of mortality in DReSS syndrome include myocardial or pulmonary lesions and hemophagocytosis. We reviewed the literature of previously reported case-series of DReSS and liver involvement,highlighting the pattern of liver damage,the treatment used,and the outcome.

急性脊髓损伤患者治疗的临床操作指南:关于MRI基线在临床治疗决策与结果预测中作用的几点建议（英文）

The objective of this guideline is to outline the role of magnetic resonance imaging(MRI) in clinical decision making and outcome prediction in patients with traumatic spinal cord injury(SCI).Methods A systematic review of the literature was conducted to address key questions related to the use of MRI in patients with traumatic SCI.This review focused on longitudinal studies that controlled for baseline neurologic status.A multidisciplinary Guideline Development Group(GDG) used this information,their clinical expertise,and patient input to develop recommendations on the use of MRI for SCI patients.Based on GRADE(Grading of Recommendation,Assessment,Development and Evaluation),a strong recommendation is worded as " we recommend," whereas a weaker recommendation is indicated by "we suggest." Results Based on the limited available evidence and the clinical expertise of the GDG,our recommendations were:(1) "We suggest that MRI be performed in adult patients with acute SCI prior to surgical intervention,when feasible,to facilitate improved clinical decision-making"(quality of evidence,very low) and(2) "We suggest that MRI should be performed in adult patients in the acute period following SCI,before or after surgical intervention,to improve prediction of neurologic outcome "(quality of evidence,low).Conclusions These guidelines should be implemented into clinical practice to improve outcomes and prognostication for patients with SCI.

早期乳腺癌最佳辅助化疗方案与人类表皮生长因子受体2阳性乳腺癌辅助靶向治疗选择：依据 ASCO 对 CCO临床实践指南的改编

目的研究加拿大安大略癌症治疗中心(CCO)关于早期乳腺癌最佳辅助化疗方案,包括人类表皮生长因子受体2(HER2)阳性乳腺癌辅助靶向治疗方案,并对其进行改编。方法按照美国临床肿瘤协会(ASCO)对其他组织临床实践指南改编的策略和程序,对CCO临床实践指南的严谨性与内容适用性进行回顾。结果基于对CCO临床实践指南内容的回顾,ASCO小组认为,CCO临床实践指南在整体上清晰全面,以最确切的科学证据为基础,为患者提供可接受的治疗选项。推荐关于辅助化疗方案的决定,应考虑到基线复发风险、毒性、利益可能性和宿主因素(如合并症)。对于高风险HER2阴性的身体状况良好的人群,蒽环类和紫杉烷治疗方案是标准治疗方案。4个周期的多西他赛和环磷酰胺治疗方案是可接受的非蒽环类治疗方案。对于高风险HER2阳性患者,推荐蒽环类与紫杉烷序贯疗法联合曲妥单抗或多西他赛、卡铂、曲妥单抗进行6个周期的治疗。对于低风险、非淋巴结转移、HER2阳性人群,推荐每周一次的紫杉醇和曲妥单抗连续进行12个周期的替代治疗。曲妥单抗应持续使用1年。不应采用铂复合盐对三阴性人群进行常规的辅助管理,除非出现有效的生存数据加以支持。

多层螺旋CT对肠管和(或)肠系膜钝性外伤手术指征评估的准确性研究

目的 探讨多层螺旋CT发现有外科手术指征的肠和（或）肠系膜钝性外伤的准确性，确定和描述肠和（或）肠系膜损伤最可靠的CT表现，评价不同水平阅片者的表现。材料和方法 本研究通过了审查委员会的审核，采用回顾性病例对照的方法研究96例经剖腹探查证实的病例：54例肠和（或）肠系膜损伤（有或无手术指征）病人[男性32例，女性22例；平均（40．4±17．6）岁，范围16～86岁]和42例没有肠和（或）肠系膜损伤病人[男性22例，女性20例；平均（36．8±20．1）岁，范围14～84岁]，

Multiple therapeutic and preventive effects of 3,3'-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia

Cruciferous vegetables belong to the plant family that has flowers with four equal-sized petals in the pattern of a crucifer cross.These vegetables are an abundant source of dietary phytochemicals,including glucosinolates and their hydrolysis products such as indole-3-carbinol（I3C） and 3,3＇-diindolylmethane（DIM）.By 2013,the total number of natural glucosinolates that have been documented is estimated to be 132.Recently,cruciferous vegetable intake has garnered great interest for its multiple health benefits such as anticancer,antiviral infections,human sex hormone regulation,and its therapeutic and preventive effects on prostate cancer and high grade prostatic intraepithelial neoplasia（HGPIN）.DIM is a hydrolysis product of glucosinolates and has been used in various trials.This review is to provide an insight into the latest developments of DIM in treating or preventing both prostate cancer and HGPIN.

Antecedents and sex/gender differences in youth suicidal behavior

Suicide is the second leading cause of death in youth globally; however, there is uncertainty about how best to intervene. Suicide rates are typically higher in males than females, while the converse is true for suicide attempts. We review this "gender paradox" in youth, and in particular, the age-dependency of these sex/gender differences and the developmental mechanisms that may explain them. Epidemiologic, genetic,neurodevelopmental and psychopathological research have identified suicidal behaviour risks arising from genetic vulnerabilities and sex/gender differences in early adverse environments, neurodevelopment, mental disorder and their complex interconnections. Further, evolving sex-/gender-defined social expectations and norms have been thought to influence suicide risk. In particular, how youth perceive and cope with threats and losses(including conforming to others' or one's own expectations of sex/gender identity) and adapt to pain(through substance use and helpseeking behaviours). Taken together, considering brain plasticity over the lifespan, these proposed antecedents to youth suicide highlight the importance of interventions that alter early environment(s)(e.g., childhood maltreatment) and/or one's ability to adapt to them. Further, such interventions may have more enduring protective effects, for the individual and for future generations, if implemented in youth.

Results of single stage exchange arthroplasty with retention of well fixed cement-less femoral component in management of infected total hip arthroplasty

AIM To investigate success of one stage exchange with retention of fixed acetabular cup.METHODS Fifteen patients treated by single stage acetabular component exchange with retention of well-fixed femoral component in infected total hip arthroplasty(THA)were retrospectively reviewed.Inclusion criteria were patients with painful chronic infected total hip.The patient had radiologically well fixed femoral components,absence of major soft tissue or bone defect compromising,and infecting organism was not poly or virulent microorganism.The organisms were identified preoperatively in14 patients(93.3%),coagulase negative Staphylococcus was the infecting organism in 8 patients(53.3%).RESULTS Mean age of the patients at surgery was 58.93(±10.67)years.Mean follow-up was 102.8 mo(36-217 mo,SD56.4).Fourteen patients had no recurrence of the infection;one hip(6.7%)was revised for management of infection.Statistical analysis using Kaplan Meier curve showed 93.3%survival rate.One failure in our series;the infection recurred after 14 mo,the patient was treated successfully with surgical intervention by irrigation,and debridement and liner exchange.Two complications:The first patient had recurrent hip dislocation 12 years following the definitive procedure,which was managed by revision THA with abductor reconstruction and constrained acetabular liner;the second complication was aseptic loosening of the acetabular component 2years following the definitive procedure.CONCLUSION Successful in management of infected THA when following criteria are met;well-fixed stem,no draining sinuses,non-immune compromised patients,and infection with sensitive organisms.

Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis： perspectives and approaches

Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

Clinical supervision for novice millennial nurses in the perinatal setting: The need for generational sensitivity

This paper reports on a qualitative research study that examined the experience of expert and novice nurses participating in a new, reflective program of “clinical supervision”, intending to facilitate the transition of new graduate nurses into the workforce. Three patterns emerged during the constructivist inquiry: readiness to reflect, valuing of clinical supervision, and sustainability of the clinical supervision model. The researchers suggest generational sensitivity as a key perspective to consider when developing engaging workplace strategies for millennial nurses. The article offers recommendations for the implementation of clinical supervision and would be of interest to nurse leaders in a clinical setting.