bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction to ICDR Arbitration
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This introductory chapter provides an overview of the International Centre for Dispute Resolution (ICDR), the American Arbitration Association’s (AAA) division focused on international disputes. Following the revision of the International Arbitration Rules in 1996–97, the ICDR was charged with all of the AAA’s international services. Importantly, the ICDR is empowered to apply any one of several sets of rules and procedures in administering international disputes. By far, the most common applicable set of rules is the ICDR Rules, closely followed by the AAA Commercial Rules. However, the ICDR might also be asked to administer an arbitration governed by one of the many industry-specific sets of rules. The chapter then traces the genesis of the ICDR Rules and major changes over time, leading up to the substantial overhaul of the ICDR Rules effected in 2014.
Article 4—Administrative Conference
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter assesses Article 4 of the 2014 ICDR Rules. Article 4 incorporates a long-standing ICDR practice by which the ICDR conducts an administrative conference before the arbitral tribunal is constituted to facilitate party discussion and agreement on issues such as arbitrator selection, mediating the dispute, process efficiencies, and any other administrative matters. No other major international arbitration rules contain a similar provision. The administrative conference affords the parties an opportunity to air their objectives for management of the case and, if possible, to reach arguments on administrative issues. Depending on the complexity of the case, and the familiarity of both sides with the factual and legal issues, the administrative conference may also permit an opportunity to arrive at stipulations of uncontested facts, identify potential witnesses, provide for advance exchange of information, and consider the possibility of utilizing a documents-only process.
Article 6—Emergency Measures of Protection
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter studies the ICDR’s provision for emergency measures in Article 6. Through the procedures detailed in Article 6, a party may apply to secure expedited emergency relief even before an arbitrator has been appointed. On receipt of such an application, the ICDR will appoint an emergency arbitrator, who is tasked with considering the application and who has the power to order interim awards, to protect or conserve property, and to make other orders of emergency relief. Importantly, a party may still choose to go to a court of competent jurisdiction to obtain emergency relief, such as a preliminary injunction, a temporary restraining order, or an order to preserve evidence. The real utility of Article 6 lies in situations in which the tribunal has not yet been appointed and a party fears that the appropriate courts will not grant interim relief or it will be ineffective.
Article 8—Consolidation
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter examines Article 8 of the 2014 ICDR Rules. Article 8 provides for consolidation of two or more proceedings upon party request with the decision on whether and how to permit consolidation to be made by a consolidation arbitrator. The ICDR ‘may appoint a consolidation arbitrator, who will have the power to consolidate two or more arbitrations pending under these Rules’, or any other set of rules administered by the AAA or ICDR, into a single arbitration. This means that, at least in theory, provided that the other requirements of Article 8 are satisfied, the consolidation arbitrator could consolidate an arbitration that is pending under two different, albeit related, sets of rules. The objective of this provision is to achieve a more time and cost-efficient resolution of the entire dispute and to avoid inconsistent decisions.
Article 13—Impartiality and Independence of Arbitrator
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter explores Article 13, which requires that arbitrators in ICDR disputes shall be impartial and independent. The importance of impartiality and independence is significant. These notions affect the very core of arbitration, including the selection of arbitrators and the subsequent process for challenging arbitrators, and even provide a potential basis for seeking to annul the resulting award. To assess an arbitrator’s independence and impartiality, Article 13 requires broad and continuous disclosure—‘at any stage during the arbitration’—which also allows the parties to determine whether they wish to challenge a named arbitrator using the procedure set out in Article 14. Ultimately, the requirements of impartiality and independence seek to ensure the integrity of the arbitral process and emanate from the arbitrators’ judicial function in resolving the dispute.
Article 15—Replacement of an Arbitrator
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter discusses Article 15 of the ICDR Rules, which addresses the replacement of an arbitrator and its consequences, such as a repetition of prior proceedings. This involves a delicate balancing act: a substitute arbitrator must be able to consider all of the details of the case, while the parties may want to avoid starting the case over or repeating significant portions of the proceedings because doing so creates time and cost burdens. Article 15(3) further provides for the possibility of a truncated tribunal in certain circumstances. Importantly, the application of Article 15(1) applies to a broad range of circumstances where: an arbitrator resigns; an arbitrator is incapable of performing the duties of an arbitrator; or an arbitrator is removed for any reason and the office becomes vacant.
Article 22—Privilege
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter explores Article 22 of the ICDR Rules, which mandates that the tribunal is to take into account applicable principles of legal privilege and provides a general guideline to the tribunal when faced with potentially inconsistent legal privilege rules being applied to different parties. Determining legal privilege issues falls within the scope of the tribunal’s broad discretion to manage the arbitral proceedings and the exchange of information and often requires the tribunal to make determinations on the availability and admissibility of evidence. Privilege issues frequently arise in international arbitrations, but resolving these issues can often be complex, as there are few established norms on how legal privilege applies across different jurisdictions. As such, inherent in the first sentence of Article 22 is the tribunal’s task of determining what the ‘applicable principles of privilege’ are.
Article 23—Hearing
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter studies Article 23, which sets out some basic procedural guidelines for the arbitral hearing—addressing such issues as notice requirements, identification of witnesses, and logistics for witness examination—and vests broad discretion in the tribunal on the conduct of the hearing. While the tribunal typically enjoys a broad discretion in laying the ‘ground rules’ for the hearing, it will also be influenced by several other factors. First, the tribunal may well decide to adopt outright, or at a minimum be guided by, international standard rules on evidential or procedural matters. Second, the arbitral procedure may be influenced by any provisions relating to hearings adopted as part of the arbitration clause or submission to arbitration. Lastly, a tribunal will take note of the provisions relating to hearings that are contained in the applicable arbitration rules.
Article 28—Waiver
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter assesses Article 28 of the ICDR Rules. It is not uncommon for a party to raise objections to the arbitration based on non-compliance with the relevant institutional rules. However, when not raised promptly, such an objection can derail an arbitral proceeding and create potential grounds on which to challenge the award. Article 28 requires that where a party knows of any non-compliance with the ICDR Rules or the parties’ arbitration agreement, but instead proceeds with the arbitration without promptly objecting in writing, it will be deemed to have waived the right to object. This general principle is also echoed in the ICDR Rules in the specific context of challenges to arbitrators and objections to jurisdiction. Ultimately, the revisions to Article 28 in the 2014 ICDR Rules reflect best practices in international arbitration and potentially broaden the effect of the waiver provision.
Article 36—Deposits
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter assesses Article 36 of the ICDR Rules. Article 36 sets out the basic rules for when deposits are to be paid as an advance on the costs of the arbitration, the consequences for non-payment, and the Administrator’s duty to account to the parties for how the deposits have been used. The advance on costs is strategically important because, unlike in litigation, it requires the parties to ‘front’ potentially significant sums in order to continue to have the dispute resolved by arbitration. This can be used by either party to try to gain leverage. The text of Article 36 was the subject of several revisions with the 2014 amendments to the ICDR Rules. A new paragraph was added to the Article, making explicit that a party’s failure to pay a required deposit can be treated as a withdrawal of the party’s claim or counterclaim.
Article 38—Exclusion of Liability
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter explores Article 38 of the ICDR Rules, which seeks to absolve the arbitrators and the ICDR Administrator of any liability in connection with the arbitration to the fullest extent allowed by the applicable law. While arbitrator immunity and that of arbitral institutions is typically dealt with in applicable national laws, Article 38 performs the important additional function of providing a contractual basis for granting immunity. The 2014 revisions to the provision made some subtle changes to the text of what is now Article 38. The revised text now excludes the waiver of liability to the extent required by the applicable law. In addition, Article 38 now explicitly provides that the arbitrators and ICDR are immune from suit and from being called as a party or witness in litigation.
Part IV Fundamental Rights and Obligations, A Substantive Obligations, 9 Equitable and Reasonable Utilization
Authors: Stephen C McCaffrey
Published: May 2019

This chapter examines the concept of equitable utilization. Equitable utilization is chiefly a doctrine governing apportionment, or allocation, of water between states sharing an international watercourse. It is a dynamic process, which depends heavily upon active cooperation between states sharing fresh water resources. A new use in one state may change the equitable utilization calculus as among all riparians and therefore should be the subject of prior notification, consultation, and, if necessary, negotiation. This is true whether the new use is made by an upstream or a downstream state: new upstream uses may have physical impacts upon those downstream; and new downstream uses may have legal impacts upon those upstream, because they may alter the equitable balance of uses in such a way as to make subsequent new uses in an upstream state inequitable.
Part IV Fundamental Rights and Obligations, D Dispute Avoidance and Settlement, 14 Dispute Avoidance and Settlement: Selected Aspects
Authors: Stephen C McCaffrey
Published: May 2019

This concluding chapter highlights two propositions concerning the avoidance and settlement of disputes, specifically in the field of international watercourses. The first proposition is that it is believed desirable that problems relating to international watercourses be resolved on the private level, through courts and administrative bodies, insofar as possible and appropriate. Private dispute resolution will usually bring relief to the individuals concerned more expeditiously than diplomatic procedures and will tend to keep disputes from becoming overblown and unnecessarily politicized. The second proposition concerns the use of expert bodies for fact-finding and resolution of disputes. The proposition is that differences and disputes can often be avoided and resolved on a non-political level through joint technical bodies, and that states sharing international watercourses should therefore make provision for the use of such entities.
Introduction
Authors: Murray Rachel
Published: May 2019

This section is an introduction to the African Charter on Human and Peoples’ Rights
Article 5
Authors: Murray Rachel
Published: May 2019

This section is about Article 5 of the African Charter on Human and Peoples’ Rights dealing with Respect of Dignity; Prohibition of Slavery and Torture and Other Forms of Ill-Treatment.
Article 8
Authors: Murray Rachel
Published: May 2019

This section is about Article 8 of the African Charter on Human and Peoples’ Rights dealing with Freedom of Conscience and Religion.
Article 9
Authors: Murray Rachel
Published: May 2019

This section is about Article 9 of the African Charter on Human and Peoples’ Rights dealing with Right to Receive Information and Freedom of Expression.
Article 10
Authors: Murray Rachel
Published: May 2019

This section is about Article 10 of the African Charter on Human and Peoples’ Rights dealing with Freedom of Association.
Article 11
Authors: Murray Rachel
Published: May 2019

This section is about Article 11 of the African Charter on Human and Peoples’ Rights dealing with Right to Assemble.
Article 12
Authors: Murray Rachel
Published: May 2019

This section is about Article 12 of the African Charter on Human and Peoples’ Rights dealing with Freedom of Movement.
Article 16
Authors: Murray Rachel
Published: May 2019

This section is about Article 16 of the African Charter on Human and Peoples’ Rights dealing with Right to Health.
Article 17
Authors: Murray Rachel
Published: May 2019

This section is about Article 17 of the African Charter on Human and Peoples’ Rights dealing with Right to Education, Cultural Life and the Promotion of Morals and Traditional Values.
Article 21
Authors: Murray Rachel
Published: May 2019

This section is about Article 21 of the African Charter on Human and Peoples’ Rights dealing with Disposal of Wealth and Natural Resources.
Article 23
Authors: Murray Rachel
Published: May 2019

This section is about Article 23 of the African Charter on Human and Peoples’ Rights dealing with Right to Peace and Security.
Article 24
Authors: Murray Rachel
Published: May 2019

This section is about Article 24 of the African Charter on Human and Peoples’ Rights dealing with Right to General Satisfactory Environment.
Articles 27–29
Authors: Murray Rachel
Published: May 2019

This section is about Articles 27–29 of the African Charter on Human and Peoples’ Rights dealing with Individual Duties.
Articles 55 and 57
Authors: Murray Rachel
Published: May 2019

This section is about Articles 55 and 57 of the African Charter on Human and Peoples’ Rights dealing with Individual Communication Procedure.
Article 59
Authors: Murray Rachel
Published: May 2019

This section is about Article 59 of the African Charter on Human and Peoples’ Rights dealing with Confidentiality and Publication.
Faecal microbiota dynamics in Cornu aspersum during dietary change and antibiotic challenge
Authors: Smith Parker N , Boomer Sarah M , Baltzley Michael J
Published: May 2019

Despite its widespread geographic distribution and applications, the herbivorous land snail Cornu aspersum represents an understudied animal host. In this study, we used a culture-based approach, in combination with a population analysis based on 16S rRNA amplicon sequencing, to describe changes in the faecal microbiota of wild-caught snails that were fed a nonsterile plant diet over a period of 21 days. At the beginning of the experiment, wild-caught snails harboured diverse populations of Gammaproteobacteria. The two most abundant genera of Gammaproteobacteria were soil-associated Pseudomonas and Buttiauxella; the latter is an understudied genus often reported in snails and slugs. During penicillin treatment, the diversity of Gammaproteobacteria in experimental snails bottlenecked, resulting in Pseudomonas takeover. Following penicillin treatment, experimental snails began to recover, with faecal samples containing pre-treatment Gammaproteobacteria groups by day 21. There was a significant difference in the colony-forming units/g across days and across treatments. Additionally, there was a significant interaction between day and treatment. The food source was not sterile and supported its own population of Gammaproteobacteria, primarily Pseudomonas, which would have been taken up by the snails daily. Given that Buttiauxella was not observed on the food source, we hypothesize that it was present and maintained within the digestive tract of C. aspersum, and this is consistent with the idea that C. aspersum maintains an endogenous gut microbiome.
Role of skeletal muscle autophagy in high-fat-diet–induced obesity and exercise
Authors: Herrenbruck Adrienne R , Bollinger Lance M
Published: May 2019

Autophagy is a complex degradation pathway responsible for clearing damaged and dysfunctional organelles. High-fat-diet–induced obesity has been shown to alter autophagy throughout the body in a tissue-specific manner. The impact of obesity on skeletal muscle autophagy has yet to be elucidated. This review examines the impact of high-fat-diet–induced obesity and exercise on skeletal muscle autophagy. Better understanding this major quality control mechanism may help develop novel therapies to combat high-fat-diet–induced obesity comorbidities.
The Impact of Malaria on Liver Enzymes: A Retrospective Cohort Study (2010–2017)
Authors: Cheaveau James , Marasinghe Dewdunee , Akakpo Samantha , Deardon Rob , Naugler Christopher , Chin Alex , Pillai Dylan R
Published: May 2019

Background

It is unclear if malaria causes deranged liver enzymes. This has implications both in clinical practice and in research, particularly for antimalarial drug development.

Method

We performed a retrospective cohort study of returning travelers (n = 4548) who underwent a malaria test and had enzymes measured within 31 days in Calgary, Canada, from 2010 to 2017. Odds ratios of having an abnormal alkaline phosphatase (ALP), alanine aminotransferases (ALT), aspartate aminotransferases (AST), and total bilirubin (TB) were calculated using multivariable longitudinal analysis with binomial response.

Results

After adjusting for gender, age, and use of hepatotoxic medications, returning travelers testing positive for malaria had higher odds of having an abnormal TB (odds ratio [OR], 12.64; 95% confidence interval [CI], 6.32–25.29; P < .001) but not ALP (OR, 0.32; 95% CI, 0.09–1.10; P = .072), ALT (OR, 1.01; 95% CI, 0.54–1.89; P = .978) or AST (OR, 1.26; 95% CI, 0.22–7.37; P = .794), compared with those who tested negative. TB was most likely to be abnormal in the “early” period (day 0–day 3) but then normalized in subsequent intervals. Returning travelers with severe malaria (OR, 2.56; 95% CI, 0.99–6.62; P = .052) had borderline increased odds of having an abnormal TB, but malaria species (OR, 0.70; 95% CI, 0.24–2.05; P = .511) did not.

Conclusions

In malaria-exposed returning travelers, the TB is abnormal, especially in the early period, but no abnormalities are seen for ALT, AST, or ALP.
Dynamic Inconsistency in Food Choice: Experimental Evidence from Two Food Deserts
Authors: Sadoff Sally , Samek Anya , Sprenger Charles
Published: May 2019

We conduct field experiments to investigate dynamic inconsistency and commitment demand in food choice. In two home grocery delivery programs, we document substantial dynamic inconsistency between advance and immediate choices. When given the option to commit to their advance choices, around half of subjects take it up. Commitment demand is negatively correlated with dynamic inconsistency, suggesting those with larger self-control problems are less likely to be aware thereof. We evaluate the welfare consequences of dynamic inconsistency and commitment policies with utility measures based on advance, immediate, and unambiguous choices. Simply offering commitment has limited welfare (and behavioural) consequences under all measures.
Infection of Select Pinaceae and Cupressaceae Seedlings to Phytophthora pinifolia
Authors: Widmer Timothy L. , Dodge Stephen C.
Published: May 2019

Phytophthora pinifolia caused a devastating disease on Monterey pine (Pinus radiata) in Chile. This pathogen has not been reported in the United States, but there is concern should it arrive. There is little information regarding other hosts besides Monterey pine that may be susceptible to this pathogen. In the present study, other potential hosts within the Pinaceae and Cupressaceae were inoculated with zoospores of P. pinifolia and observed for symptoms and infection after 4 weeks. Similar to Monterey pine, knobcone (Pinus attenuata), bishop (P. muricata), and ponderosa (P. ponderosa) pines were highly infectious, whereas several important species such as loblolly pine (P. taeda) and Douglas fir (Pseudotsuga menziesii) showed no infection. P. pinifolia was also not recovered from slash (Pinus elliottii) and eastern white (P. strobus) pines. This study is important because it demonstrates other economically important tree hosts are at risk by P. pinifolia, should it enter the United States.
The Co-occurrence of Pediatric Chronic Pain and Depression
Authors: Soltani Sabine , Kopala-Sibley Daniel C. , Noel Melanie
Published: May 2019

Objectives:

Internalizing mental health issues co-occur with pediatric chronic pain at high rates and are linked to worse pain and functioning. Although the field has prioritized anxiety and posttraumatic stress disorder, little is known about co-occurring depression and chronic pain in youth, despite its high prevalence. The purpose of this narrative review was to examine the existing literature on the co-occurrence of pediatric chronic pain and depressive disorders and symptoms and propose a conceptual model of mutual maintenance to guide future research.

Methods:

The literature from both fields of pediatric pain and developmental psychology were searched to review the evidence for the co-occurrence of pediatric chronic pain and depression. Conceptual models of co-occurring mental health issues and chronic pain, as well as child depression, were reviewed. From both literatures, we provide evidence for a number of proposed child, parent, and neurobiological factors that may serve to mutually maintain both conditions over time. On the basis of this evidence, we propose a conceptual model of mutual maintenance and highlight several areas for future research in this area.

Results:

Evidence was found for the prevalence of depression in pediatric chronic pain as well as the co-occurrence of both conditions. The key mutually maintaining factors identified and proposed included neurobiological, intrapersonal (eg, cognitive biases, sleep disturbances, emotion regulation, and behavioral inactivation), and interpersonal (eg, parent mental health and pain, genes, and parenting) factors.

Discussion:

Given the dearth of research on mutual maintenance in this area, this review and conceptual model could drive future research in this area. We argue for the development of tailored treatments for this unique population of youth to improve outcomes.
Lever sign test: is it sensitive for the diagnosis of anterior cruciate ligament disruption?
Authors: Fahmy Fahmy Samir , Fathi Hossam
Published: May 2019

Background:

Anterior cruciate ligament (ACL) tear is a common knee injury with various manual tests used for clinical diagnosis. The aim of this prospective study was to evaluate the lever sign test sensitivity as a new clinical test for diagnosis of ACL disruptions compared to other manual diagnostic tests.

Methods:

One hundred patients with chronic ACL tears were included in this study between January 2017 and March 2018. The mean age was 29.1±8.2 yr. Four clinical tests (anterior drawer, Lachman test, pivot shift, and lever sign) were obtained in all patients by two different clinicians. The contralateral uninjured knees were used as controls for comparison. The sensitivity of these tests was estimated with recording of the interobserver reliability for lever sign test. Statistically significant differences between the lever test and other clinical tests were assessed using chi-square analysis.

Results:

The recorded sensitivities of anterior drawer, pivot-shift, and Lachman tests were 82%, 88%, and 91%, respectively. The sensitivity of the lever sign test was much lower (34%) with 100% interrater reliability. There was a statistically significant difference between the lever sign test and other physical tests (P-value<0.05).

Conclusions:

The lever sign test has much lower sensitivity than other clinical diagnostic tests in patients with chronic ACL lesions. More biomechanical studies should be carried out to prove the validity of this test for the diagnosis of ACL injuries.

Level of evidence:

Level III.
Are Nonpharmacologic Interventions for Chronic Low Back Pain More Cost Effective Than Usual Care? Proof of Concept Results From a Markov Model
Authors: Herman Patricia M. , Lavelle Tara A. , Sorbero Melony E. , Hurwitz Eric L. , Coulter Ian D.
Published: May 2019

Study Design.

Markov model.

Objective.

Examine the 1-year effectiveness and cost-effectiveness (societal and payer perspectives) of adding nonpharmacologic interventions for chronic low back pain (CLBP) to usual care using a decision analytic model-based approach.

Summary of Background Data.

Treatment guidelines now recommend many safe and effective nonpharmacologic interventions for CLBP. However, little is known regarding their effectiveness in subpopulations (e.g., high-impact chronic pain patients), nor about their cost-effectiveness.

Methods.

The model included four health states: high-impact chronic pain (substantial activity limitations); no pain; and two others without activity limitations, but with higher (moderate-impact) or lower (low-impact) pain. We estimated intervention-specific transition probabilities for these health states using individual patient-level data from 10 large randomized trials covering 17 nonpharmacologic therapies. The model was run for nine 6-week cycles to approximate a 1-year time horizon. Quality-adjusted life-year weights were based on six-dimensional health state short form scores; healthcare costs were based on 2003 to 2015 Medical Expenditure Panel Survey data; and lost productivity costs used in the societal perspective were based on reported absenteeism. Results were generated for two target populations: (1) a typical baseline mix of patients with CLBP (25% low-impact, 35% moderate-impact, and 40% high-impact chronic pain) and (2) high-impact chronic pain patients.

Results.

From the societal perspective, all but two of the therapies were cost effective (<$50,000/quality-adjusted life-year) for a typical patient mix and most were cost saving. From the payer perspective fewer were cost saving, but the same number was cost-effective. Assuming all patients in the model have high-impact chronic pain increases the effectiveness and cost-effectiveness of most, but not all, therapies indicating that substantial benefits are possible in this subpopulation.

Conclusion.

Modeling leverages the evidence produced from clinical trials to provide more information than is available in the published studies. We recommend modeling for all existing studies of nonpharmacologic interventions for CLBP.

Level of Evidence: 4
Abdominal Vascular Injury During Posterior Lumbar Discectomy, Experience from Three Cases and Review of Literature
Authors: Goel Anshul , Kumar Pranaw , Bahadur Raj
Published: May 2019

Study Design.

Case series and review of literature.

Objective.

To report three cases of vascular injury during posterior lumbar disc surgery, two of these occurred during open discectomy, and one during an endoscopic surgery. Aim is to highlight importance of early diagnosis and prompt steps taken to prevent morbidity and mortality.

Summary of Background Data.

Vascular injury during lumbar discectomy is rare injury. Also no case has been reported so far occurring during an endoscopic discectomy.

Methods.

Three patients were treated for lumbar intervertebral disc prolapse, two had undergone open posterior discectomy while the third patient underwent endoscopic discectomy and all of them were diagnosed to have suffered an abdominal vascular injury.

Results.

In two cases pseudo-aneurysm was found while third case was diagnosed as an arterio-venous fistula. All the three cases were managed with endovascular stenting and followed for a minimum period of 2 years. No further complications were detected.

Conclusion.

Vascular injury during a disc surgery is difficult to diagnose due to the rarity of occurrence and subtle signs which need to be recognized to start early management.

Level of Evidence: 5
Anatomy and Biomechanics of the Sacroiliac Joint
Authors: Zlomislic Vinko , Garfin Steve R.
Published: May 2019

Sacroiliac (SI) joint pain is a difficult problem that is becoming increasingly recognized for its contribution to low back pain. In certain circumstances it may present independently. However, in many scenarios the SI joint represents one of many factors contributing to axial back pain and its various referral patterns. Low back pain remains a significant burden on the health care system, accounting for ∼12 million physician office visits per year in the United States. It remains among the leading causes of disability, with expenditures in excess of $80 billion dollars every year. Surgical management of low back pain results in variable success rates ranging from 35% to 89%, suggesting that the etiology of back pain is complex, often multifactorial, and frequently not clearly known. Studies have shown that SI joint pathology may present in association with, or contribute directly to, back pain as often as 20% to 45% of the time. Despite this, the SI joint is often overlooked as a contributing source of back pain. It is necessary to maintain an index of suspicion, as well as understand the relevant anatomy, biomechanics, and clinical presentation involved in SI joint mediated pain, to be able to arrive at an appropriate diagnosis. This section presents a review of SI joint anatomy and biomechanics to establish a foundation necessary for understanding the clinical manifestations of SI joint dysfunction and treatment options.
At-Risk Drinking Is Independently Associated With Acute Kidney Injury in Critically Ill Patients
Authors: Gacouin Arnaud , Lesouhaitier Mathieu , Frerou Aurelien , Painvin Benoit , Reizine Florian , Rafi Sonia , Maamar Adel , Le Tulzo Yves , Tadié Jean Marc
Published: May 2019

Objectives:

Unhealthy use of alcohol and acute kidney injury are major public health problems, but little is known about the impact of excessive alcohol consumption on kidney function in critically ill patients. We aimed to determine whether at-risk drinking is independently associated with acute kidney injury in the ICU and at ICU discharge.

Design:

Prospective observational cohort study.

Setting:

A 21-bed polyvalent ICU in a university hospital.

Patients:

A total of 1,107 adult patients admitted over a 30-month period who had an ICU stay of greater than or equal to 3 days and in whom alcohol consumption could be assessed.

Interventions:

None.

Measurements and Main Results:

We assessed Kidney Disease Improving Global Outcomes stages 2–3 acute kidney injury in 320 at-risk drinkers (29%) and 787 non–at-risk drinkers (71%) at admission to the ICU, within 4 days after admission and at ICU discharge. The proportion of patients with stages 2–3 acute kidney injury at admission to the ICU (42.5% vs 18%; p < 0.0001) was significantly higher in at-risk drinkers than in non–at-risk drinkers. Within 4 days and after adjustment on susceptible and predisposing factors for acute kidney injury was performed, at-risk drinking was significantly associated with acute kidney injury for the entire population (odds ratio, 2.15; 1.60–2.89; p < 0.0001) in the subgroup of 832 patients without stages 2–3 acute kidney injury at admission to the ICU (odds ratio, 1.44; 1.02–2.02; p = 0.04) and in the subgroup of 971 patients without known chronic kidney disease (odds ratio, 1.92; 1.41–2.61; p < 0.0001). Among survivors, 22% of at-risk drinkers and 9% of non–at-risk drinkers were discharged with stages 2–3 acute kidney injury (p < 0.001).

Conclusions:

Our results suggest that chronic and current alcohol misuse in critically ill patients is associated with kidney dysfunction. The systematic and accurate identification of patients with alcohol misuse may allow for the prevention of acute kidney injury.
Severe gastrointestinal toxicity of MEK inhibitors
Authors: Mourad Nadim , Lourenço Nelson , Delyon Julie , Eftekhari Pirayeh , Bertheau Philippe , Allayous Clara , Ballon Alice , Pagès Cécile , Allez Matthieu , Lebbé Céleste , Baroudjian Barouyr
Published: May 2019

Gastrointestinal toxicities of MEK inhibitors in melanoma patients are frequent. In clinical trials, the most common digestive adverse events were nausea, vomiting, and diarrhoea. However, severe toxicities such as colitis and gastrointestinal perforation, some with fatal outcomes, have been reported. These rare but severe adverse events are not well described. We performed a retrospective analysis of all patients with stage IV and unresectable stage III melanoma treated with a MEK inhibitors at Saint-Louis Hospital, Paris, between 1 August 2013 and 15 October 2018. Among 119 patients exposed to MEK inhibitors, 78 were treated with trametinib, 19 with cobimetinib, four with binimetinib, and 18 patients with two different MEK inhibitors at separate times. All grade digestive adverse events were observed in 39 (32.7%) patients. Grade 3 and 4 adverse events occurred in 6 (5%) patients: 2 (1.7%) developed perforations, 3 (2.5%) had colitis and 1 (0.8%) had grade 4 diarrhoea. These adverse events were all reversible following a permanent discontinuation of the MEK inhibitors, or a temporary interruption followed by resumption at a dose lower than conventional posology. There were no fatal outcomes; however one patient had a permanent ileostomy. The mechanism underlying these toxicities is not well known. Clinicians should be aware of such toxicities.
The programmed cell death protein-1/programmed cell death ligand 1 expression, CD3+ T cell infiltration, NY-ESO-1 expression, and microsatellite instability phenotype in primary cutaneous melanoma and mucosal melanoma and their clinical significance and prognostic value: a study of 89 consecutive cases
Authors: Ren Yu , Lv Qing , Yue Wuheng , Liu Baorui , Zou Zhengyun
Published: May 2019

We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), and NY-ESO-1 antigen; the infiltration of CD3+ T cells; and the microsatellite instability (MSI) phenotype, as well as the relationship of each factor to survival in malignant melanoma patients. Malignant melanoma samples from 89 patients were stained by immunohistochemistry to evaluate PD-1, PD-L1, CD3+ tumor-infiltrating lymphocytes (TILs), NY-ESO-1, and MSI. PD-1 and PD-L1 were expressed in 19.1 and 32.6% of the 89 samples, respectively. There was a significant correlation between PD-1 and PD-L1 expression (r = 0.207, P = 0.046). High infiltration of CD3+ T cells was observed in 41.6% of the samples, and increased cell infiltration was associated with increased PD-1 expression (P = 0.001). NY-ESO-1 antigen was detected in 13.5% of all samples, and the expression of NY-ESO-1 was positively correlated with the expression of PD-1 (P < 0.001). In our research, MSI was detected in 18 samples (20.2%). Survival analysis showed that a high infiltration of CD3+ T cells was related to longer progression-free survival (PFS) [24.0 months, 95% confidence interval (CI): 7.4–40.6 vs. 11.0 months, 95% CI: 7.1–12.9, P = 0.031], similarly, the median overall survival (OS) of the CD3+ T cell high-infiltration patients was also longer (53.0 vs. 38.0 months), but with no statistical significance (P = 0.200). The results for the immune markers mentioned above provide a theoretical basis for the prognosis and immunotherapy selection of malignant melanoma patients.
Disseminated intravascular coagulation and melanoma: a novel case occurring in metastatic melanoma with BRAF and NRAS mutations and systematic review
Authors: Haggstrom Lucy , Duong Tuan Anh , Thomas Benjamin , Brungs Daniel , Aghmesheh Morteza , Parmar Gurdeep
Published: May 2019

Disseminated intravascular coagulation is a complex and potentially lethal complication of malignancy, in which the fundamental abnormality is excessive activation of the coagulation system. It is a rare complication of melanoma which can be difficult to diagnose in some circumstances, leading to delay in treatment. Herein, we describe the first case of disseminated intravascular coagulation occurring in BRAF and NRAS-mutant metastatic melanoma, and systematically review the literature regarding disseminated intravascular coagulation in melanoma. This review summarizes the reported cases of disseminated intravascular coagulation in melanoma and those secondary to the novel treatment of melanoma, and explores the pathophysiology of disseminated intravascular coagulation in melanoma, highlighting the key role of expression of markers of coagulation and fibrinolysis in disseminated intravascular coagulation, as well as more widely in melanoma. Current limitations in the literature are also identified and discussed, particularly with respect to improving the management of this lethal complication. Disseminated intravascular coagulation is a rare complication of melanoma that typically portends poor prognosis.
Is an Acetabular Cage and Cement Fixation Sufficiently Durable for the Treatment of Destructive Acetabular Metastases?
Authors: Rowell Philip , Lowe Martin , Sommerville Scott , Dickinson Ian
Published: May 2019

Background

Destructive bony acetabular metastases cause pain, pathological fractures, and loss of mobility. Although multiple fixation options are available, we have favored a rigid stainless steel partial pelvic cage for acetabular fixation in these patients; however, little is known about the durability of this approach.

Question/purposes

(1) How common was loss of fixation in a small series of metastatic acetabular defects treated with an acetabular cage and cemented total hip replacement? (2) What is the implant survival free from reoperation or revision at 2 and 4 years using a competing-risks survivorship estimator in patients thus treated? (3) What complications were associated with the treatment? (4) What level of postoperative mobility was achieved?

Methods

Between 2006 and 2017, we treated all acetabular metastases that needed surgical intervention, not amenable to conventional cemented THA alone with our single technique of acetabular partial pelvic cage and cemented total hip replacement. We treated 47 hips in 46 patients whose acetabular metastasis led to acetabular collapse or who were unresponsive to nonoperative measures of radiation therapy and analgesia. Routine followup occurred at 3 and 12 months; 17 of 46 patients (37%) died before 1 year, and all other patients were followed beyond 1 year. Only one patient who remains alive has not been seen in the past 5 years. Loss of fixation was determined by radiological or clinical signs of cage loosening. Survivorship free from reoperation or revision at 2 and 4 years was determined using competing-risks analysis. We did not assess patient-reported outcomes, but we did have data on the proportion of patients who were able to ambulate in the community and if so, what assistive devices they used, which we obtained by chart review.

Results

One patient experienced cage loosening identified 8 years postoperatively as a result of local disease progression and has been managed with observation. No patients underwent revision for loss of acetabular fixation. The cumulative incidence of reoperation or revision was 8% at 2 years (95% CI, 3.6–12.6) and 16% at 4 years (95% CI, 9.2–23.2). Four patients had postoperative dislocations, of which three underwent reoperation. One patient developed a postoperative deep infection and underwent reoperation. One patient died within 30 days of surgery. Only one patient did not ambulate in the community postoperatively; 23 ambulated independently, 10 with the use of a walking stick and 12 using a walker.

Conclusions

In this small series, we found this approach sufficiently durable to continue its use for patients with acetabular metastases with collapse or those not responding to nonoperative measures. However, comparison studies are needed to determine whether it is superior or inferior to other available alternatives.

Level of Evidence

Level IV, therapeutic study.
Therapeutic Drug Monitoring of Oral Anticancer Drugs: The Dutch Pharmacology Oncology Group–Therapeutic Drug Monitoring Protocol for a Prospective Study
Authors: Groenland Stefanie L. , van Eerden Ruben A. G. , Verheijen Remy B. , Koolen Stijn L. W. , Moes Dirk Jan A. R. , Desar Ingrid M. E. , Reyners Anna K. L. , Gelderblom Hans J. , van Erp Nielka P. , Mathijssen Ron H. J. , Huitema Alwin D. R. , Steeghs Neeltje ,   on behalf of the Dutch Pharmacology Oncology Group (DPOG)
Published: May 2019

Background:

Oral anticancer drugs show a high interpatient variability in pharmacokinetics (PK), leading to large differences in drug exposure. For many of these drugs, exposure has been linked to efficacy and toxicity. Despite this knowledge, these drugs are still administered in a one-size-fits-all approach. Consequently, individual patients have a high probability to be either underdosed, which can lead to decreased antitumor efficacy, or overdosed, which could potentially result in increased toxicity. Therapeutic drug monitoring (TDM), personalized dosing based on measured drug levels, could be used to circumvent underdosing and overdosing and thereby optimize treatment outcomes.

Methods:

In this prospective clinical study (www.trialregister.nl; NL6695), the feasibility, tolerability, and efficacy of TDM of oral anticancer drugs will be evaluated. In total, at least 600 patients will be included for (at least) 23 different compounds. Patients starting regular treatment with one of these compounds at the approved standard dose can be included. PK sampling will be performed at 4, 8, and 12 weeks after the start of treatment and every 12 weeks thereafter. Drug concentrations will be measured, and trough concentrations (Cmin) will be calculated. In cases where Cmin falls below the predefined target and acceptable toxicity, a PK-guided intervention will be recommended. This could include emphasizing compliance, adapting concomitant medication (due to drug–drug interactions), instructing to take the drug concomitant with food, splitting intake moments, or recommending a dose increase.

Discussion:

Despite a strong rationale for the use of TDM for oral anticancer drugs, this is currently not yet widely adopted in routine patient care. This prospective study will be a valuable contribution to demonstrate the additional value of dose optimization on treatment outcome for these drugs.
The “Heart Valve Clinic” Pathway for the Management of Frail Patients With Valvular Heart Disease: From “One for All” to “All for One”
Authors: Pavone Natalia , Chiariello Giovanni A. , Bruno Piergiorgio , Marzetti Emanuele , Spalletta Claudio , Nesta Marialisa , Mazza Andrea , Cammertoni Federico , Colizzi Christian , Iafrancesco Mauro , Pasquini Annalisa , Di Molfetta Arianna , Burzotta Francesco , Massetti Massimo
Published: May 2019

Valvular heart disease (VHD) is frequently diagnosed in old patients with clinical evidence of heart failure. This elderly population typically presents a high prevalence of frailty and comorbidities, which are associated with increased operative risk for surgical and percutaneous procedures. Recently, the Euro Heart Survey reported a clear gap between treatment guidelines and their application in the “real world”. A more realistic approach to the treatment of older VHD patients treatment, mostly if associated with heart failure, is advocated. A multidisciplinary approach, as obtained with the Heart Valve Clinic methodology (intended to put the patient in the “center” of the scene and the specialists “around him”), has been applied in a group of 79 patients, aged >70 years, with symptomatic VHD, divided in 2 groups according to their frailty status (58 robust and 21 frail). No in-hospital mortality and no difference in late mortality and complications were observed. Infections were more frequent (14.3 vs. 1.7 %; P = 0.02) in frail patients. In patients with postoperative complications, serum levels of interleukin 6 (67.6 vs. 49.6; P = 0.01) and of CAF (C-terminal agrin fragment) as sarcopenia marker (67.9 vs. 62.0; P = 0.04) were higher than that in uncomplicated patients. This study was designed to determine the outcomes of the multidimensional geriatric assessment in the management of older patients with heart failure eligible for heart valve surgery. Geriatric assessment and measurement of inflammatory and sarcopenia markers may represent valid tools for a more realistic evaluation of elderly patients with VHD.
Phacotrabeculectomy in Eyes With Uveitic Glaucoma: A Retrospective Case-Control Study
Authors: Wadke Vidya , Lingam Vijaya , George Ronnie , George Amala E. , Ganesh Sudha K. , Biswas Jyotirmay , Balekudaru Shantha
Published: May 2019

Precis:

Phacotrabeculectomy with adjunctive mitomycin C is a good option for the management of coexisting cataract and glaucoma. Strict preoperative control of inflammation and close follow-up are essential in the management of eyes with uveitic glaucoma (UG).

Purpose:

The purpose of this study was to compare the outcomes of phacotrabeculectomy with adjunctive antimetabolites in the management of patients with UG and patients with primary open-angle glaucoma (POAG).

Materials and Methods:

A retrospective case-control study of 112 patients with UG and 120 patients with POAG who underwent phacotrabeculectomy with mitomycin C and had a follow-up of ≥12 months between January 2000 and June 2015 was performed. Patients who had undergone intraocular surgery or cyclodestructive procedures earlier were excluded. The primary outcome was intraocular pressure (IOP) control; secondary outcomes included visual acuity and complication rates.

Results:

IOP control was similar at the final visit in the UG group (14.52±6.74 mm Hg) and the POAG group (14.39±4.18 mm Hg) (P=0.867). Kaplan-Meier survival analysis showed a cumulative probability of survival (IOP: 6 to 18 with or without medications) in 71% and 77% at the end of 5 years (P=0.094) in the UG and POAG groups, respectively. Visual outcomes were worse in the UG group (0.5±0.68 logMAR units), as compared with the POAG group (0.27±0.47 logMAR units) (P=0.002). Complications such as cystoid macular edema (P=0.025) and posterior capsular opacification (P=0.004) were more common in the UG group. Recurrence of inflammation occurred in 34 eyes (30.04%) in the UG group.

Conclusion:

Meticulous control of perioperative and postoperative inflammation could have contributed to the favorable long-term outcomes of phacotrabeculectomy in UG, as compared with POAG.