bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiation risk amongst orthopaedic surgeons – Do we know the risk?
Authors: Gowda Sushmith R , Mitchell Chris J , Abouel-Enin Sherif , Lewis Charlotte
Published: June 2018

Radiation risk amongst orthopaedic surgeons and theatre personnel is increasing with increased use of fluoroscopy imaging. Increased radiation risk has been shown to be associated with an increased risk of malignancies, ocular and thyroid disorders. Very high exposures have been reported in spinal surgery and during intra-medullary nailing. With an increase in modern and percutaneous methods, the use of intra-operative fluoroscopy has increased as well. The aim of this article was to review the available evidence of radiation risk amongst healthcare personnel. A systematic search was carried out in PubMED, CINAHL and Cochrane on intra-operative radiation in trauma and orthopaedic operating room. Inclusion criteria were clinical studies and systematic reviews reporting on radiation exposure, fluoroscopy time and references to specific safety guidelines. This article highlights the safety aspects of radiation protection and harmful effects of radiation during orthopaedic procedures. The responsibility to minimise radiation exposure in operating theatre lies with the team within the operating room.
Reliability evaluation of four different assays for therapeutic drug monitoring of infliximab levels
Authors: Pérez Irene , Fernández Lidia , Sánchez-Ramón Silvia , Alba Cristina , Zatarain Ana , Cañas Mercedes , López Olga N. , Olivares David , Rey Enrique , Taxonera Carlos
Published: June 2018

Background:

The aim of this study was to evaluate reliability of four different assays for measuring infliximab trough levels and antibodies to infliximab (ATI).

Methods:

In this non-interventional, cross-sectional study including IBD patients, infliximab levels and ATI were measured using four different assays: Lisa-Tracker, Promonitor, Q-Inflixi and Sanquin. Reliability and agreement for infliximab levels was assessed using the intraclass correlation coefficient (ICC) and Bland–Altman plots. Qualitative agreement for infliximab (based on a pre-established target window of trough levels between 3 µg/ml and 7 µg/ml) and for ATI were estimated by Cohen’s kappa.

Results:

Serum samples of 84 IBD patients were evaluated for infliximab using the four assays. Reliability was ‘substantial’ between Lisa-Tracker versus Promonitor and ‘almost perfect’ between the remaining assay pairs, with ICCs [95% confidence interval (CI)] ranging from 0.93 (0.70–0.97) for Lisa-Tracker versus Promonitor to 0.97 (0.95–0.98) for Q-Inflixi versus Sanquin. Bland–Altman plots showed significant bias between assays except Promonitor versus Q-Inflixi, which had excellent agreement. The greatest differences in mean infliximab were found between Promonitor versus Lisa-Tracker (–0.91 µg/ml) and Lisa-Tracker versus Q-Inflixi (0.69 µg/ml). Qualitative agreement for infliximab was ‘almost perfect’ for Promonitor versus Q-Inflixi (kappa 0.84) and Q-Inflixi versus Sanquin (kappa 0.81), and ‘substantial’ for the remaining pairs. More than 10% of patients who had infliximab levels within the target interval by Lisa-Tracker had suboptimal concentrations (<3 µg/ml) with Promonitor and Q-Inflixi. Furthermore, 11% of patients within the target interval by Q-Inflixi had supra-optimal levels (>7 µg/ml) by Lisa-Tracker. In the remaining paired comparisons, fewer than 5% of patients were placed in different subgroups. Qualitative agreement for ATI fluctuated between ‘moderate’ and ‘almost perfect’.

Conclusions:

All four assays seem suitable for therapeutic drug monitoring of infliximab. Promonitor and Q-Inflixi had the best agreement, making those assays fully interchangeable. Systematic biases between Lisa-Tracker with Promonitor and Q-Inflixi suggest that these assays should not be interchanged during the follow up of an individual patient.
Sources of variability in hospital administrative data: Clinical coding of postoperative ileus
Authors: Resslar Mary A , Ivanitskaya Lana V , Perez Mario A , Zikos Dimitrios
Published: June 2018

Background:

Multiple studies have questioned the validity of clinical codes in hospital administrative data. We examined variability in reporting a postoperative ileus (POI).

Objective:

We aimed to analyse sources of coding variations to understand how clinical coding professionals arrive at POI coding decisions and to verify existing knowledge that current clinical coding practices lack standardised applications of regulatory guidelines.

Method:

Two medical records (cases 1 and 2) were provided to 15 clinical coders employed by a midsize nonprofit hospital in the northwest region of the United States. After coding these cases, the study participants completed a survey, reported on the application of guidelines, and participated in a focus group led by a health information management regulatory compliance expert.

Results:

Only 5 of the 15 clinical coders correctly indicated no POI complication in case 1 where the physician documentation did not establish a link between the POI as a complication of care and the surgery. In contrast, 13 of the 15 study participants correctly coded case 2, which included clear physician documentation and contained the clinical parameters for the coding of the POI as a complication of care. Clinical coder education, credentials, certifications, and experience did not relate to the coding performance. The clinical coders inconsistently prioritised coding rules and valued experience more than education.

Conclusion and implications:

The application of International Classification of Diseases, Ninth Revision, Clinical Modification; coding conventions; Centers for Medicare and Medicaid Services coding guidelines; and American Hospital Association coding clinic advice was subject to the clinical coders’ interpretation; they perceived them as conflicting guidance. Their reliance on subjective experience in dealing with this conflicting guidance may limit the accuracy of reporting outcomes of clinical performance.
Exploring phase control in a quantum dot light-emitting diode
Authors: Al Husseini H , Abdalah SF , Al Naimee KAM , Meucci R , Arecchi FT
Published: June 2018

We report phase control in a periodically driven chaotic nanosystem consisting of a quantum dot light-emitting diode. Such a dynamical system is a class C laser, whence the charactering features are intrinsically chaotic. Phase control relies on the addition of small parametric harmonic perturbations with adjustable phase. Phase control is demonstrated by changing both frequency and strength of the controlling perturbations. Our results show that phase control has two crucial effects on a quantum dot light-emitting diode. First, it can enhance the spiking behavior in either regular or chaotic regimes; second, it is able to turn periodic behavior to chaotic behavior with a minimal perturbation when a resonance condition at half of the driving frequency is achieved.
High Concentration of Insulin Induces MUC5AC Expression via Phosphoinositide 3 Kinase/AKT and Mitogen-activated Protein Kinase Signaling Pathways in Human Airway Epithelial Cells
Authors: Na Hyung Gyun , Kim Yong-Dae , Bae Chang Hoon , Choi Yoon Seok , Jin Hyun Jung , Shin Kyeong-Cheol , Song Si-Youn
Published: June 2018

Background

Insulin is involved in a glucose homeostatic regulation and a cellular metabolism via phosphorylation of phosphoinositide 3 kinase (PI3K) pathway and mitogen-activated protein kinase (MAPK) pathway. Hyperinsulinemia reduces insulin sensitivity and is an obvious potential factor affecting airway inflammation in chronic airway diseases. MUC5AC is a major secreted mucin, which plays a critical role in inflammatory response in the respiratory tract. However, the relationship between insulin and MUC5AC expression has not been studied.

Objective

This study investigated the effect and the brief signaling pathway of high concentration of insulin (HI) on MUC5AC expression in human airway epithelial cell.

Methods

In NCI-H292 cells and primary cultures of normal nasal epithelial cells, the effect and signaling pathway of HI on MUC5AC expression were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA).

Results

HI significantly increased MUC5AC expression and activated PI3K/AKT, extracellular signal-related kinase 1/2 (ERK1/2) and p38 MAPKs. The specific PI3K and AKT inhibitor as well as knockdown of AKT1 and AKT2 by the respective siRNAs significantly blocked HI-mediated expression of MUC5AC. Meanwhile, the specific ERK1/2 MAPK and p38 MAPK inhibitor as well as knockdown of ERK1, ERK2, and p38 MAPK by the respective siRNAs also attenuated HI-induced expression of MUC5AC.

Conclusion

The results of this study suggest that HI induces MUC5AC expression via PI3K/AKT and MAPK signaling pathways in human airway epithelial cells.
Calgranulin C (S100A12) Is Differentially Expressed in Subtypes of Chronic Rhinosinusitis
Authors: Pulsipher Abigail , Davis Brock M. , Smith Kristine A. , Ashby Shaelene , Qin Xuan , Firpo Matt , Orlandi Richard R. , Alt Jeremiah A.
Published: June 2018

Background

Calgranulin C (S100A12) is an innate immune peptide at the air–mucosal interface associated with neutrophil involvement, which when overexpressed has been implicated as a biomarker of inflammatory diseases. Decreased epithelial expression of certain innate immune peptides has been reported in chronic rhinosinusitis (CRS). We hypothesized that S100A12 is differentially expressed in the sinonasal mucosa of patients with CRS compared to controls and that S100A12 is a potential biomarker of CRS-specific quality of life (QOL) and disease severity.

Methods

A prospective observational study was conducted which included 70 patients: 17 controls, 28 having CRS without (CRSsNP), and 25 with (CRSwNP) nasal polyps. The expression of S100A12 and human neutrophil elastase (HNE) was assessed in the anterior ethmoid tissues from all patients using enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analyses. Disease-specific QOL (Rhinosinusitis Disability Index) and disease severity (computed tomography [CT] and endoscopy) were evaluated and correlated to the expression levels of S100A12.

Results

S100A12 and HNE were significantly elevated in patients with CRSsNP compared to normal controls ( P < .05 and P < .001, respectively) and patients with CRSwNP ( P < .05 and P < .001, respectively), as measured by ELISA and IHC analyses. Patients with CRS exhibited worse CRS-specific disease severity compared to normal controls ( P < .05), and the increased protein levels of S100A12 were significantly correlated to disease severity, represented by CT scores ( P < .05).

Conclusions

S100A12 is differentially expressed in CRS subtypes and is significantly elevated in patients with CRSsNP and associated with CRS-specific disease severity.
Intravenous treprostinil via an implantable pump in pediatric pulmonary arterial hypertension
Authors: Desole Susanna , Richter Manuel Jonas , Heine Alexander , Ewert Ralf
Published: June 2018

Intravenous prostacyclin‐based therapy improves survival in children with pulmonary arterial hypertension (PAH), but is typically administered via an external infusion pump, which places a considerable burden on the patient. Implanted pumps may overcome some of the limitations of external pumps. We describe the first long‐term use of an implanted pump for intravenous treprostinil delivery in a pediatric patient with PAH. Our patient was experiencing marked dyspnea on exertion despite triple combination therapy with bosentan, sildenafil, and inhaled iloprost. Parenteral prostacyclin‐based therapy was discussed and the patient rejected options involving external pumps; she finally chose intravenous treprostinil delivery via an implanted pump (LENUS Pro®; fixed flow rate; 20 ml reservoir). The patient underwent pump implantation in July 2012 (aged 14 years) under general anesthesia with no peri‐ or postoperative complications. She showed marked improvements in fatigue and dyspnea over the subsequent weeks, and her inhaled iloprost regimen was slowly decreased and stopped after six months. During follow‐up, the pump showed an unexpected, progressive increase in flow rate that allowed a treprostinil dose of 170 ng/kg/min to be achieved, but at the cost of shortened intervals between refills. The pump was therefore replaced in August 2017 with a newer model with an adjustable flow rate (Siromedes®). A catheter dislocation was corrected under local anesthesia one week after the replacement surgery. The patient is currently receiving treprostinil 170 ng/kg/min with percutaneous refills every 12–13 days. Thus, implantable pumps might be a valuable alternative to external pumps for treprostinil infusion in pediatric PAH.
Strong inverse associations of Mediterranean diet, physical activity and their combination with cardiovascular disease: The Seguimiento Universidad de Navarra (SUN) cohort
Authors: Alvarez-Alvarez Ismael , de Rojas Javier Pérez , Fernandez-Montero Alejandro , Zazpe Itziar , Ruiz-Canela Miguel , Hidalgo-Santamaría María , Bes-Rastrollo Maira , Martínez-González Miguel Á
Published: June 2018

Background

Inverse associations of the Mediterranean diet (MedDiet) and physical activity with cardiovascular disease have been previously reported. We investigated the individual and combined contributions of both to this inverse association in a Mediterranean cohort.

Design

We used data from 19,536 participants from a prospective cohort of Spanish university graduates, the ‘Seguimiento Universidad de Navarra’ (SUN) cohort, followed up between December 1999 and December 2016.

Methods

Adherence to the MedDiet was obtained from a 136-item validated food-frequency questionnaire and categorized in tertiles using four previously reported dietary scores. A validated questionnaire assessed the physical activity levels according to volume, intensity and frequency.

Results

Participants were followed up during a median time of 10.4 years. Compared with the lowest category of adherence to the MedDiet (≤3 in the Mediterranean Diet Score), higher adherence (6–9 points) was strongly inversely associated with cardiovascular disease (multivariable adjusted hazard ratio = 0.33; 95% confidence interval (CI) 0.20–0.55). Also, engaging in an active lifestyle (6–8 points in an eight-item score) compared with low activity (<2 points) was associated with a reduced risk of incident cardiovascular disease (hazard ratio = 0.43; 95% CI 0.20–0.90). Greater adherence to the MedDiet and engaging in high levels of active lifestyle showed a 75% relatively reduced risk of cardiovascular disease (hazard ratio = 0.25; 95% CI 0.13–0.48).

Conclusions

The combined effect of adherence to the MedDiet and adopting an active lifestyle showed a synergistic inverse association with cardiovascular disease risk.
The role of hydroxychloroquine in catastrophic antiphospholipid syndrome case: Series of two case reports and review of literature
Authors: Hindi Zakaria , Hussein Mosa , Gad Abdallah , Khaled Abdallah A. , Zahoor Talal
Published: June 2018

Catastrophic antiphospholipid syndrome is a rare disorder that remains under-recognized causing a high mortality rate even with treatment. Factors such as infections and systemic lupus erythematosus flare play as an inciting event in the thrombotic crisis which underlies catastrophic antiphospholipid syndrome. The use of plasmapheresis has improved the outcome of such cases with a reduction in mortality rate from over 50% to less than 30%, according to some studies. However, the definitive treatment of this disabling and fatal condition remains an area warranting research. Case 1. A case of 32-year-old female with a background of epilepsy and recurrent abortions who presented with difficulty in breathing, dry cough, and bilateral lower limb swelling. The patient initially received treatment with cyclophosphamide and systemic corticosteroids after being diagnosed with systemic lupus erythematosus. She also underwent plasmapheresis for suspected pulmonary hemorrhage as her condition deteriorated rapidly requiring intensive care. The diagnosis was revised as catastrophic antiphospholipid syndrome given the typical multi-organ involvement, namely, cerebritis, Libman–Sacks endocarditis, and nephritis apart from the pulmonary involvement. Eventually, hydroxychloroquine was added to the regimen which led to a remarkable improvement in her condition after a few days. Case 2. A case of 28-year-old female with history of recurrent abortions presented with abdominal pain and was admitted as a case of pancreatitis. The patient received intravenous fluids and analgesics with no significant improvement. Later, she developed multi-organ failure requiring critical care. Given her history and clinical presentation along with the multi-organ involvement in an acute setting, she underwent extensive workup that favored catastrophic antiphospholipid syndrome and she was started on Aspirin initially, and then, hydroxychloroquine was administered. Few days after initiation, her condition improved markedly and with complete resolution of her abdominal symptoms.

Hydroxychloroquine’s antithrombotic effect in synergy with other therapies has been observed in our cases. Yet, its role in the early course of catastrophic antiphospholipid syndrome merits further investigation.
Singing, sharing, soothing – biopsychosocial rationales for parental infant-directed singing in neonatal pain management
Authors: Ullsten Alexandra , Eriksson Mats , Klässbo Maria , Volgsten Ulrik
Published: June 2018

Infant-directed singing is a medium for parents and infants to communicate in a mutual relationship. Parental infant-directed singing is a multisensory, biopsychosocial communication that applies to ill and vulnerable hospitalised infants. The primary musical features of infant-directed singing are ideal for emotional coordination and sharing between parent and infant without the risk of over-stimulation. In this article, we suggest that parental infant-directed singing is regarded as a nonpharmacological emotion regulation intervention, which may modify the painful experience for both the infant and the parent before, during and after painful procedures in the neonatal intensive care context. Parents have the biopsychosocial resources to alleviate their infant’s pain through infant-directed singing, if they are empowered to do so and coached in this process. A music therapist specialised in neonatal music therapy methods can mentor parents in how to use entrained and attuned live lullaby singing in connection to painful procedures. Pain and the vast amount of painful procedures early in infancy, combined with early parent–infant separation and lack of parental participation in the care of the infant during neonatal intensive care, place arduous strain on the new family’s attachment process and on the infant’s and parents’ mental health, both from a short and long-term perspective. Therefore, we argue with biopsychosocial rationales, that live parental infant-directed singing should be promoted in neonatal pain care worldwide. Consequently, parents should be welcomed round the clock and invited as prescribed pain management for their infant.
Does Marital Duration Moderate (Dis)Similarity Effects of Personality on Marital Satisfaction?
Authors: Abe Shingo , Oshio Atsushi
Published: June 2018

This study examined the actor, partner, and (dis)similarity effects of personality on marital satisfaction, considering the interaction with marital duration. Participants were 749 Japanese married couples. The results of an actor–partner interdependence model, which includes interaction with marital duration, showed that there was little interaction between actor and partner effects and marital duration, indicating that both one’s own and the partner’s personality have consistent effects on satisfaction throughout marital duration. In contrast, similarity effects did interact with marital duration. In shorter marital duration, similar couples were less satisfied, whereas similarity had no effect on satisfaction in longer marital duration. We discuss the possible influence of the transition from a romantic relationship to a marital relationship.
Digital Political Talk and Political Participation: Comparing Established and Third Wave Democracies
Authors: Vaccari Cristian , Valeriani Augusto
Published: June 2018

We investigate whether and how informal political talk on digital media contributes to citizens’ political participation with unique surveys based on samples representative of Internet users in seven Western democracies. We show that political talk on both social networking sites and mobile instant messaging platforms is positively associated with institutional and extra-institutional political participation. However, the relationship between talk on social networking sites and both types of participation is significantly stronger in established democracies (Denmark, France, United Kingdom, and United States) than in “third wave” democracies (Greece, Poland, and Spain). By contrast, the strength of the relationship between political talk on mobile instant messaging platforms and participation is not significantly different when comparing established and more recent democracies. These findings suggest that informal political talk on digital platforms can contribute to citizens’ participatory repertoires and that different institutional settings, in combination with different technological affordances, play an important role in shaping these patterns.
Surgical, Radiographic, and Patient-Related Risk Factors for Proximal Junctional Kyphosis: A Meta-Analysis
Authors: Kim Jun S. , Phan Kevin , Cheung Zoe B. , Lee Nam , Vargas Luilly , Arvind Varun , Merrill Robert K. , Gidumal Sunder , Di Capua John , Overley Samuel , Dowdell James , Cho Samuel K.
Published: June 2018

Study Design:

Meta-analysis.

Objective:

Proximal junctional kyphosis (PJK) is a complication of surgical management for adult spinal deformity with a multifactorial etiology. Many risk factors are controversial and their relative importance are not fully understood. We aimed to identify the surgical, radiographic, and patient-related risk factors associated with PJK and proximal junctional failure (PJF).

Methods:

A systematic literature search was performed using PubMed, Cochrane Database of Systematic Reviews, and EMBASE. The inclusion criteria included prospective randomized control trials and prospective/retrospective cohort studies of adult patients with radiographic evidence of PJK, which was defined as a proximal junctional sagittal Cobb angle ≥10° and at least 10° greater than the preoperative measurement. Studies required a minimum of 10 patients and 12 months of follow-up.

Results:

A total of 14 unique studies, including 1908 patients were included. The pooled analysis showed significant differences between the PJK and non-PJK groups in age (weighted mean difference [WMD] −3.80; P = .03), prevalence of osteopenia/osteoporosis (odds ratio [OR] 1.99; P = .0004), preoperative sagittal vertical axis (SVA) (WMD −17.52; P = .02), preoperative lumbar lordosis (LL) (WMD −1.22; P = .002), pedicle screw instrumentation at the upper instrumented vertebra (UIV) (OR 1.67; P = .02), change in SVA (WMD −11.87; P = .01), fusion to sacrum/pelvis/ilium (OR 2.14; P < .00 001), change in LL (WMD −5.61; P = .01), and postoperative SVA (WMD −7.79; P = .008).

Conclusions:

Our meta-analysis suggests that age, osteopenia/osteoporosis, high preoperative SVA, high postoperative SVA, low preoperative LL, use of pedicle screws at the UIV, SVA change/correction, LL change/correction, and fusion to sacrum/pelvis/iliac region are risk factors for PJK.
Clinical Evaluation of an Arthroscopic Knotless Suprapectoral Biceps Tenodesis Technique: Loop ’n’ Tack Tenodesis
Authors: Duerr Robert A. , Nye Darin , Paci James M. , Akhavan Sam
Published: June 2018

Background:

Pathology of the long head of the biceps tendon is a well-known cause of shoulder pain that is commonly managed with arthroscopic suprapectoral biceps tenodesis when conservative treatment fails.

Purpose:

To present an arthroscopic knotless suprapectoral biceps tenodesis technique known as “Loop ’n’ Tack” tenodesis and to report the clinical outcomes of patients with a minimum 2 years of follow-up.

Study Design:

Case series; Level of evidence, 4.

Methods:

A retrospective review of all patients who had undergone Loop ’n’ Tack tenodesis between January 2009 and May 2014 was completed. Charts were reviewed, and patients were contacted for demographic data, time from surgery, concomitant procedures, and workers’ compensation status, as well as visual analog scale for pain, American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation, and University of California, Los Angeles (UCLA) scores.

Results:

Complete follow-up evaluations were performed for 59 of 68 patients (87%). Mean follow-up was 43 months. A majority (88%) of patients had at least 1 additional procedure performed at the time of biceps tenodesis. The mean ASES shoulder score improved from 42.6 preoperatively to 91.0 postoperatively ( P < .001), and 54 of 59 patients (91.5%) had a good/excellent outcome, with a UCLA shoulder score >27 and ASES shoulder score >70. Three patients (5%) reported biceps cramping pain with overuse, and 2 (3.3%) reported intermittent anterior shoulder pain. No patients had developed a “Popeye” deformity at final clinical examination, and 97% reported that they were overall satisfied with the procedure.

Conclusion:

The Loop ’n’ Tack tenodesis technique results in a high rate of patient satisfaction, significant improvement in shoulder outcome scores, and a low incidence of postoperative pain, with no reoperations for biceps-related pathology.
Do Articular-Sided Partial-Thickness Rotator Cuff Tears After a First-Time Traumatic Anterior Shoulder Dislocation in Young Athletes Influence the Outcome of Surgical Stabilization?
Authors: Rahu Madis , Kartus Jüri-Toomas , Põldoja Elle , Pedak Kirsti , Kolts Ivo , Kask Kristo
Published: June 2018

Background:

Because of the high risk for redislocations after a first-time traumatic anterior shoulder dislocation with conservative treatment, recent publications have recommended early arthroscopic intervention, especially for young athletes. Concomitant rotator cuff tendon damage may occur when the shoulder dislocates; however, its presence and influence on clinical results have not been well described in this patient category.

Hypothesis:

In opposition to current opinion, a substantial number of articular-sided partial-thickness rotator cuff tears (APTRCTs) would be found at surgery after a first-time traumatic anterior shoulder dislocation in young athletes. However, the impact of these injuries on 2-year postoperative results would be negligible.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Sixteen male patients (mean age, 21 years [range, 16-25 years]) with a first-time traumatic anterior shoulder dislocation without bony Bankart lesions were included in this study. The indications for surgical treatment were age less than 25 years and being active in collision or contact sports at a competitive level. Arthroscopic surgery was performed at a mean 7.8 days (range, 2-14 days) after injury. Rowe and American Shoulder and Elbow Surgeons (ASES) scores as well as range of motion were evaluated at a minimum 2 years after an arthroscopic Bankart procedure, and a comparison of the clinical results between patients with and without APTRCTs was conducted.

Results:

An anterior-inferior capsulolabral injury was found in all patients. There were no bony Bankart lesions. An APTRCT was found in 9 of the 16 patients. At 2 years after surgical treatment, there were no significant differences between the patients with and without APTRCTs in terms of the Rowe score (90.0 and 87.1, respectively; P = .69) and ASES score (94.6 and 90.4, respectively; P = .67).

Conclusion:

APTRCTs were found in the superior part of the shoulder joint after a first-time traumatic anterior shoulder dislocation in a majority of young male athletes treated with surgical stabilization. There were no significant differences found between patients with and without APTRCTs in terms of the Rowe and ASES scores at 2 years after surgical treatment.
The emerging accountability regimes for the Sustainable Development Goals and policy integration: Friend or foe?
Authors: Karlsson-Vinkhuyzen Sylvia , Dahl Arthur L , Persson Åsa
Published: June 2018

The 17 Sustainable Development Goals and the full Agenda 2030 in which they are embedded are aspirational and intended to be both transformational and integrative in a number of ways. The need for integration across policy domains is stressed throughout the agenda. The Sustainable Development Goals are also accompanied by an emerging system for follow-up and review centered on a long list of indicators that are intended to enable countries to be accountable towards their citizens. There is, however, in the accountability literature indication that some accountability mechanisms can be counterproductive for integrative policies. This paper is centered around the question whether an accountability regime, and if so how, is compatible with a high degree of policy integration both conceptually and in the context of the Sustainable Development Goals. We approach this question through looking both at the literature on integrative governance and some of the central concepts it covers such as (environmental) policy integration and mainstreaming, and the accountability literature. This enables us to provide an analytical framework for evaluating the potential of the emerging accountability regimes for the Sustainable Development Goals to enhance more integrated policy making and action. We conclude that there are little or no strong hierarchical elements of accountability relationships at the global level which can be good news for more integrative policies – but only if there is a strong sense of shared responsibility among actors at all levels, available information on the types of behavioural efforts that support integration, and accountholders that take an active interest in integration. At the national level, there may be hierarchical accountability mechanisms with sanction possibilities that may discourage integration. Here, those who hold actors to account can counteract this if they have deeper understanding of the underlying interlinkages among the goals and targets, and based on this, engage in accountability mechanisms.
Distinct roles of mesenchymal stem and progenitor cells during the development of acute myeloid leukemia in mice
Authors: Xiao Pingnan , Sandhow Lakshmi , Heshmati Yaser , Kondo Makoto , Bouderlique Thibault , Dolinska Monika , Johansson Anne-Sofie , Sigvardsson Mikael , Ekblom Marja , Walfridsson Julian , Qian Hong
Published: June 2018

Key Points

MLL-AF9 AML cell–induced BM niche alteration is correlated with leukemia burden. Ebf2 + MSPCs participate in AML niche formation, and Ebf2+ cell depletion accelerates AML development.
Risk stratification of smoldering multiple myeloma: predictive value of free light chains and group-based trajectory modeling
Authors: Wu Vernon , Moshier Erin , Leng Siyang , Barlogie Bart , Cho Hearn Jay , Jagannath Sundar , Madduri Deepu , Mazumdar Madhu , Parekh Samir , Chari Ajai
Published: June 2018

Key Points

FLCr ≥100 and BMPC ≥60% identify high-risk SMM, although with more modest median TTP and 2-year PD than previously published. Baseline immunoparesis, eMP, eHb, and edFLC can help identify an ultra-high-risk SMM cohort.
Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: a multisite study
Authors: Muhlebach Marianne S. , Hatch Joseph E. , Einarsson Gisli G. , McGrath Stef J. , Gilipin Deirdre F. , Lavelle Gillian , Mirkovic Bojana , Murray Michelle A. , McNally Paul , Gotman Nathan , Davis Thomas Sonia , Wolfgang Matthew C. , Gilligan Peter H. , McElvaney Noel G. , Elborn J. Stuart , Boucher Richard C. , Tunney Michael M.
Published: June 2018

Anaerobic and aerobic bacteria were quantitated in respiratory samples across three cystic fibrosis (CF) centres using extended culture methods. Subjects aged 1–69 years who were clinically stable provided sputum (n=200) or bronchoalveolar lavage (n=55). 18 anaerobic and 39 aerobic genera were cultured from 59% and 95% of samples, respectively; 16 out of 57 genera had a ≥5% prevalence across centres.

Analyses of microbial communities using co-occurrence networks in sputum samples showed groupings of oral, including anaerobic, bacteria, whereas typical CF pathogens formed distinct entities.Pseudomonaswas associated with worse nutrition and F508del genotype, whereas anaerobe prevalence was positively associated with pancreatic sufficiency, better nutrition and better lung function. A higher total anaerobe/total aerobe CFU ratio was associated with pancreatic sufficiency and better nutrition. Subjects grouped by factor analysis who had relative dominance of anaerobes over aerobes had milder disease compared with aPseudomonas-dominated group with similar proportions of subjects that were homozygous for F508del.

In summary, anaerobic bacteria occurred at an early age. In sputum-producing subjects anaerobic bacteria were associated with milder disease, suggesting that targeted eradication of anaerobes may not be warranted in sputum-producing CF subjects.
Profiling of healthy and asthmatic airway smooth muscle cells following interleukin-1β treatment: a novel role for CCL20 in chronic mucus hypersecretion
Authors: Faiz Alen , Weckmann Markus , Tasena Haitatip , Vermeulen Corneel J. , Van den Berge Maarten , ten Hacken Nick H.T. , Halayko Andrew J. , Ward Jeremy P.T. , Lee Tak H. , Tjin Gavin , Black Judith L. , Haghi Mehra , Xu Cheng-Jian , King Gregory G. , Farah Claude S. , Oliver Brian G. , Heijink Irene H. , Burgess Janette K.
Published: June 2018

Chronic mucus hypersecretion (CMH) contributes to the morbidity and mortality of asthma, and remains uncontrolled by current therapies in the subset of patients with severe, steroid-resistant disease. Altered cross-talk between airway epithelium and airway smooth muscle cells (ASMCs), driven by pro-inflammatory cytokines such as interleukin (IL)-1β, provides a potential mechanism that influences CMH. This study investigated mechanisms underlying CMH by comparing IL-1β-induced gene expression profiles between asthma and control-derived ASMCs and the subsequent paracrine influence on airway epithelial mucus productionin vitro.

IL-1β-treated ASMCs from asthmatic patients and healthy donors were profiled using microarray analysis and ELISA. Air–liquid interface (ALI)-cultured CALU-3 and primary airway epithelial cells were treated with identified candidates and mucus production assessed.

The IL-1β-inducedCCL20expression and protein release was increased in ASMCs from moderate compared with mild asthmatic patients and healthy controls.IL-1β induced lowerMIR146Aexpression in asthma-derived ASMCs compared with controls. DecreasedMIR146Aexpression was validatedin vivoin bronchial biopsies from 16 asthmatic patientsversus39 healthy donors. miR-146a-5p overexpression abrogated CCL20 release in ASMCs. CCL20 treatment of ALI-cultured CALU-3 and primary airway epithelial cells induced mucus production, while CCL20 levels in sputum were associated with increased levels of CMH in asthmatic patients.

Elevated CCL20 production by ASMCs, possibly resulting from dysregulated expression of the anti-inflammatory miR-146a-5p, may contribute to enhanced mucus production in asthma.
Development and validation of a radiological diagnosis model for hypersensitivity pneumonitis
Authors: Salisbury Margaret L. , Gross Barry H. , Chughtai Aamer , Sayyouh Mohamed , Kazerooni Ella A. , Bartholmai Brian J. , Xia Meng , Murray Susan , Myers Jeffrey L. , Lagstein Amir , Konopka Kristine E. , Belloli Elizabeth A. , Sheth Jamie S. , White Eric S. , Holtze Colin , Martinez Fernando J. , Flaherty Kevin R.
Published: June 2018

High-resolution computed tomography (HRCT) may be useful for diagnosing hypersensitivity pneumonitis. Here, we develop and validate a radiological diagnosis model and model-based points score.

Patients with interstitial lung disease seen at the University of Michigan Health System (derivation cohort) or enrolling in the Lung Tissue Research Consortium (validation cohort) were included. A thin-section, inspiratory HRCT scan was required. Thoracic radiologists documented radiological features.

The derivation cohort comprised 356 subjects (33.9% hypersensitivity pneumonitis) and the validation cohort comprised 424 subjects (15.5% hypersensitivity pneumonitis). An age-, sex- and smoking status-adjusted logistic regression model identified extent of mosaic attenuation or air trapping greater than that of reticulation (“MA-AT>Reticulation”; OR 6.20, 95% CI 3.53–10.90; p<0.0001) and diffuse axial disease distribution (OR 2.33, 95% CI 1.31–4.16; p=0.004) as hypersensitivity pneumonitis predictors (area under the receiver operating characteristic curve 0.814). A model-based score >2 (1 point for axial distribution, 2 points for “MA-AT>Reticulation”) has specificity 90% and positive predictive value (PPV) 74% in the derivation cohort and specificity 96% and PPV 44% in the validation cohort. Similar model performance is seen with population restriction to those reporting no exposure (score >2: specificity 91%).

When radiological mosaic attenuation or air trapping are more extensive than reticulation and disease has diffuse axial distribution, hypersensitivity pneumonitis specificity is high and false diagnosis risk low (<10%), but PPV is diminished in a low-prevalence setting.
Prevalence, characteristics and management of frequently exacerbating asthma patients: an observational study in Sweden (PACEHR)
Authors: Janson Christer , Lisspers Karin , Ställberg Björn , Johansson Gunnar , Thuresson Marcus , Telg Gunilla , Larsson Kjell
Published: June 2018

The aim of the study was to investigate the prevalence, management and characteristics of asthma patients with frequent exacerbations.

Data from asthma patients (aged ≥18 years) identified in primary care medical records were linked to Swedish national health registries. Exacerbations were defined as hospitalisations, emergency visits and/or collection of oral steroids. Frequent exacerbations were defined as two or more exacerbations per year during the 3-year observation period.

Of 18 724 asthma patients, 81.49% had no exacerbations and 6.3% had frequent exacerbations in the year prior to the index date. Frequent exacerbations were observed yearly for 1.8% of the patients. Frequent exacerbators were older, more often females, and had increased eosinophil and neutrophil counts, lower lung function, and more comorbidities than patients without exacerbations. There was a slight increase in asthma medication claims and a slight decrease in physician visits compared with baseline, both in the group with and the group without frequent exacerbations.

Patients with frequent exacerbations were characterised by greater age, female predominance, high eosinophil and neutrophil counts, and high prevalence of comorbidities. This study indicates that the Swedish healthcare system lacks efficiency to adjust treatment and management for this patient group. With new treatment options targeting severe asthma available, identification of these patients should be in focus to ensure reduction of exacerbations.
Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS
Authors: Grégoire Murielle , Uhel Fabrice , Lesouhaitier Mathieu , Gacouin Arnaud , Guirriec Marion , Mourcin Frederic , Dumontet Erwan , Chalin Arnaud , Samson Michel , Berthelot Laure-Line , Tissot Adrien , Kerjouan Mallorie , Jouneau Stéphane , Le Tulzo Yves , Tarte Karin , Zmijewski Jaroslaw W. , Tadié Jean-Marc
Published: June 2018

Exaggerated release of neutrophil extracellular traps (NETs) along with decreased NET clearance and inability to remove apoptotic cells (efferocytosis) may contribute to sustained inflammation in acute respiratory distress syndrome (ARDS). Recent studies in experimental models of ARDS have revealed the crosstalk between AMP-activated protein kinase (AMPK) and high-mobility group box 1 (HMGB1), which may contribute to effectiveness of efferocytosis, thereby reducing inflammation and ARDS severity.

We investigated neutrophil and NET clearance by macrophages from control and ARDS patients and examined how bronchoalveolar lavage (BAL) fluid from control and ARDS patients could affect NET formation and efferocytosis. Metformin (an AMPK activator) and neutralising antibody against HMGB1 were applied to improve efferocytosis and NET clearance.

Neutrophils from ARDS patients showed significantly reduced apoptosis. Conversely, NET formation was significantly enhanced in ARDS patients. Exposure of neutrophils to ARDS BAL fluid promoted NET production, while control BAL fluid had no effect. Macrophage engulfment of NETs and apoptotic neutrophils was diminished in ARDS patients. Notably, activation of AMPK in macrophages or neutralisation of HMGB1 in BAL fluid improved efferocytosis and NET clearance.

In conclusion, restoration of AMPK activity with metformin or specific neutralisation of HMGB1 in BAL fluid represent promising therapeutic strategies to decrease sustained lung inflammation during ARDS.
Stability or improvement in forced vital capacity with nintedanib in patients with idiopathic pulmonary fibrosis
Authors: Flaherty Kevin R. , Kolb Martin , Vancheri Carlo , Tang Wenbo , Conoscenti Craig S. , Richeldi Luca
Published: June 2018

In the Phase III INPULSIS® trials, nintedanib reduced the annual rate of decline in forced vital capacity (FVC)versusplacebo in patients with idiopathic pulmonary fibrosis (IPF).

We conductedpost hocanalyses of the distribution of changes in FVC in the INPULSIS® trials and FVC changes in the open-label extension trial INPULSIS®-ON in subgroups of patients based on whether patients had shown an improvement or no decline in FVC in INPULSIS®. Analyses were descriptive.

Based on the annual rate of change in FVC, 158 of 638 patients (24.8%) treated with nintedanib and 38 of 423 patients (9.0%) treated with placebo had an improvement/no decline in FVC in the INPULSIS® trials. In patients whose FVC improved/did not decline, median (interquartile range) improvements in FVC at week 52 were 76.5 (31–152) mL and 57.5 (31–103) mL in the nintedanib and placebo groups, respectively. Changes in FVC from baseline to week 48 of INPULSIS®-ON were similar in patients whose FVC improved or declined in the preceding INPULSIS® trial.

In the INPULSIS® trials, treatment with nintedanib resulted in a greater proportion of patients with IPF showing an improvement/no decline in FVC compared to taking placebo. Mechanisms underlying improvement in FVC in patients with IPF are unknown.
Cannons and sparrows: an exact maximum likelihood non-parametric test for meta-analysis of k 2 × 2 tables
Authors: Paul Lawrence M.
Published: June 2018

Background

The use of meta-analysis to aggregate multiple studies has increased dramatically over the last 30 years. For meta-analysis of homogeneous data where the effect sizes for the studies contributing to the meta-analysis differ only by statistical error, the Mantel–Haenszel technique has typically been utilized. If homogeneity cannot be assumed or established, the most popular technique is the inverse-variance DerSimonian–Laird technique. However, both of these techniques are based on large sample, asymptotic assumptions and are, at best, an approximation especially when the number of cases observed in any cell of the corresponding contingency tables is small.

Results

This paper develops an exact, non-parametric test based on a maximum likelihood test statistic as an alternative to the asymptotic techniques. Further, the test can be used across a wide range of heterogeneity. Monte Carlo simulations show that for the homogeneous case, the ML-NP-EXACT technique to be generally more powerful than the DerSimonian–Laird inverse-variance technique for realistic, smaller values of disease probability, and across a large range of odds ratios, number of contributing studies, and sample size. Possibly most important, for large values of heterogeneity, the pre-specified level of Type I Error is much better maintained by the ML-NP-EXACT technique relative to the DerSimonian–Laird technique. A fully tested implementation in the R statistical language is freely available from the author.

Conclusions

This research has developed an exact test for the meta-analysis of dichotomous data. The ML-NP-EXACT technique was strongly superior to the DerSimonian–Laird technique in maintaining a pre-specified level of Type I Error. As shown, the DerSimonian–Laird technique demonstrated many large violations of this level. Given the various biases towards finding statistical significance prevalent in epidemiology today, a strong focus on maintaining a pre-specified level of Type I Error would seem critical.
Sustained complete response of advanced hepatocellular carcinoma with metronomic capecitabine: a report of three cases
Authors: Brandi Giovanni , Venturi Michela , De Lorenzo Stefania , Garuti Francesca , Frega Giorgio , Palloni Andrea , Garajovà Ingrid , Abbati Francesca , Saccoccio Gioconda , Golfieri Rita , Pantaleo Maria Abbondanza , Barbera Maria Aurelia
Published: June 2018

Background

Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer‐related death. Sorafenib, a multitarget angiogenesis inhibitor, is an approved frontline treatment for advanced HCC in Western countries, although a complete response (CR) to treatment is infrequently reported. Capecitabine, an oral fluoropyrimidine, has been shown to be effect in both treatment‐naïve patients and those previously treated with sorafenib. To date, however, only one case of sustained CR to metronomic capecitabine has been reported.

Case presentation

We describe three cases of advanced HCC treated with metronomic capecitabine where a CR was obtained. In the first case, capecitabine was administered as first line therapy; in the second case, capecitabine was used after intolerance to sorafenib; while in the third case, capecitabine was administered after sorafenib failure.

Conclusion

Capecitabine is a potentially important treatment option for patients with advanced HCC and may even represent a cure in certain cases.