bluuebunny/crossref_metadata_2025 huggingface dataset:
A War of Position? The Thatcher Government’s Preparation for the 1984 Miners’ Strike
Authors: Vinen Richard
Published: January 2019

It has sometimes been suggested that the government of Margaret Thatcher responded to the miners’ strike of 1984/5 with plans that had been conceived long in advance. This article argues that Conservatives certainly discussed the prospect of a strike from the mid-1970s. However, they did not have clearly worked-out plans or much confidence in their ability to win such a dispute, and they became even more cautious after their humiliating retreat when faced with the threat of a strike in February 1981. Stockpiling coal was, initially, designed to deter a strike rather than to defeat one. Only slowly did some Tories reconcile themselves to the prospect that there was likely to be a strike and that 1984 was the least bad time to face it. Furthermore, Margaret Thatcher herself was not always keen to confront the miners and many of those who did the most to prepare and execute government strategy were not Thatcherites; some were civil servants rather than politicians.
Vedolizumab in Combination With Corticosteroids for Induction Therapy in Crohn’s Disease: A Post Hoc Analysis of GEMINI 2 and 3
Authors: Sands Bruce E , Van Assche Gert , Tudor David , Akhundova-Unadkat Gamar , Curtis Rebecca I , Tan Tjoeke
Published: January 2019

Background

Combined therapy with vedolizumab and corticosteroids may improve clinical response or remission in Crohn’s disease. The aim of this study is to assess efficacy and safety/tolerability of vedolizumab plus stable doses of corticosteroids at baseline during induction therapy in moderately to severely active Crohn’s disease.

Methods

A post hoc exploratory analysis was performed on data from GEMINI 2 (NCT00783692) and GEMINI 3 (NCT01224171), which assessed outcomes following induction therapy over 6- and 10-week periods, respectively. Patients receiving vedolizumab or placebo were stratified by corticosteroid use at baseline. Efficacy endpoints were clinical remission (CR; Crohn’s Disease Activity Index [CDAI] score ≤150 points) and enhanced clinical response (ECR; decrease of ≥100 points in CDAI score from baseline), assessed at week 6 (GEMINI 2 and GEMINI 3) and week 10 (GEMINI 3). Safety endpoints included the incidence of adverse events.

Results

Vedolizumab plus corticosteroids resulted in higher CR rates than placebo plus corticosteroids at week 6 in GEMINI 2 and at week 6 and week 10 in GEMINI 3. More patients receiving vedolizumab plus corticosteroids achieved CR at week 6 in GEMINI 2 and at week 10 in GEMINI 3 than patients receiving vedolizumab alone. Vedolizumab plus corticosteroids also resulted in significantly higher ECR rates than placebo plus corticosteroids at all timepoints in both studies. More patients receiving vedolizumab plus corticosteroids achieved higher ECR rates at week 6 in GEMINI 2 and at week 10 in GEMINI 3 than patients receiving vedolizumab alone. Adverse event incidence was similar across groups.

Conclusions

Vedolizumab in combination with stable doses of corticosteroids at baseline may improve induction of clinical response or remission in moderately to severely active Crohn’s disease.

Trial registration numbers

NCT00783692, NCT01224171.
When phenotypes fail to illuminate underlying genetic processes in fish and fisheries science
Authors: Kuparinen Anna , Hutchings Jeffrey A
Published: January 2019

Advances in genetic and genomic technologies have become widely available and have potential to provide novel insights into fish biology and fisheries science. In the present overview, we explore cases for which genomic analyses have proven instrumental in the rejection of hypotheses that have been well-motivated based on phenotypic and ecological properties of individuals and populations. We focus on study systems for which information derived using genomic tools contradicts conclusions drawn from traditional fisheries science methodologies and assumptions. We further illustrate the non-intuitive interplay of genomics and ecology in Atlantic salmon (Salmo salar L.) owing to the recently detected genetic architecture of age at maturity in this species. To this end, we explore a salmon management strategy applied in Québec, Canada and find that management measures aimed at protecting large, old individuals can lead to unexpected and undesired outcomes. Finally, we envisage ways in which genomic tools could be used more effectively in contemporary fisheries research and how their application could illuminate the ecological and evolutionary drivers of species and ecosystem dynamics.
Fishers’ knowledge improves the accuracy of food web model predictions
Authors: Bentley Jacob W , Serpetti Natalia , Fox Clive , Heymans Johanna J , Reid David G
Published: January 2019

Fisher's knowledge offers a valuable source of information to run parallel to observed data and fill gaps in our scientific knowledge. In this study we demonstrate how fishers' knowledge of historical fishing effort was incorporated into an Ecopath with Ecosim (EwE) model of the Irish Sea to fill the significant gap in scientific knowledge prior to 2003. The Irish Sea model was fitted and results compared using fishing effort time-series based on: (i) scientific knowledge, (ii) fishers' knowledge, (iii) adjusted fishers' knowledge, and (iv) a combination of (i) and (iii), termed “hybrid knowledge.” The hybrid model produced the best overall statistical fit, capturing the biomass trends of commercially important stocks. Importantly, the hybrid model also replicated the increase in landings of groups such as “crabs & lobsters” and “epifauna” which were poorly simulated in scenario (i). Incorporating environmental drivers and adjusting vulnerabilities in the foraging arena further improved model fit, therefore the model shows that both fishing and the environment have historically influenced trends in finfish and shellfish stocks in the Irish Sea. The co-production of knowledge approach used here improved the accuracy of model simulations and may prove fundamental for developing ecosystem-based management advice in a global context.
Towards a Discourse Approach to Critical Lexicography
Authors: Chen Wenge
Published: January 2019

Ideology and power, the vital concerns of critical lexicography, are aspects of a dictionary that a lexicographer and a discerning dictionary user have to encounter in any serious lexicographical enterprise (Kachru 1995); however, critical lexicography as a theme did not receive much attention until Kachru and Kahane (1995). This term later appeared in Hornscheidt (2011) and Moon (2014). However, to date there has not been any systematic theoretical exemplification of what critical lexicography is and how critical lexicographical research is done. Additionally, the scope and function of critical lexicography is relatively limited when we consider the global context, since it fails to take into account theoretical and methodological inspirations from other disciplines such as Critical Discourse Studies and/or Postcolonial Studies, which would make it more theoretically robust and analytically explanatory. With this gap in mind, this paper proposes a discourse approach to Critical Lexicography, termed Critical Lexicographical Discourse Studies (CLDS), as a response to the call for lexicographers’ ‘social accountability’. Specifically, the article puts forward a definition of CLDS and its key concepts, denotes its ontological, epistemological and methodological orientations, delineates its principles, proposes a tentative analytic framework and demonstrates a simplified case study. The article argues that a discourse approach to critical lexicography opens up space to understand different meaning-making practices and contestation in lexicography. In doing so, this article contributes to the development of international (English) lexicography and the language(s) it represents.
Animal Research Pathology: Regulatory and Safety Considerations
Authors: Wallace J M , Trundy R L
Published: January 2019

Animal research pathology encompasses a wide array of procedures and may involve work with a variety of animal species and hazards. To protect laboratory personnel and ensure data integrity, pathologists must be familiar with the activities performed in their laboratories and the applicable regulatory and safety requirements. Failure to address issues proactively may result in exposure of personnel to hazardous materials and/or collection of data in a manner that does not conform to animal welfare or quality control standards. This manuscript provides a brief introduction to important animal research pathology regulatory and safety considerations. The importance of close communication between the principal investigator, pathologist, laboratory personnel, Institutional Animal Care and Use Committee, and institutional safety office/experts is emphasized and a mechanism for improving communication is discussed.
Rapid Boosting of HIV-1 Neutralizing Antibody Responses in Humans Following a Prolonged Immunologic Rest Period
Authors: Spearman Paul , Tomaras Georgia D , Montefiori David C , Huang Ying , Elizaga Marnie L , Ferrari Guido , Alam S Munir , Isaacs Abby , Ahmed Hasan , Hural John , McElrath M Juliana , Ouedraogo Laissa , Pensiero Michael , Butler Chris , Kalams Spyros A , Overton Edgar Turner , Barnett Susan W ,   HVTN 088 Protocol Team and the NIH/NIAID HIV Vaccine Trials Network
Published: January 2019

Background

The durability and breadth of human immunodeficiency virus type 1 (HIV-1)–specific immune responses elicited through vaccination are important considerations in the development of an effective HIV-1 vaccine. Responses to HIV-1 envelope subunit protein (Env) immunization in humans are often described as short-lived.

Methods

We enrolled 16 healthy volunteers who had received priming with an HIV-1 subtype B Env vaccine given with MF59 adjuvant 5–17 years previously and 20 healthy unprimed volunteers. Three booster immunizations with a heterologous subtype C trimeric gp140 protein vaccine were administered to the primed group, and the same subtype C gp140 protein vaccination regimen was administered to the unprimed subjects.

Results

Binding antibodies and neutralizing antibodies to tier 1 viral isolates were detected in the majority of previously primed subjects. Remarkably, a single dose of protein boosted binding and neutralizing antibody titers in 100% of primed subjects following this prolonged immunologic rest period, and CD4+ T-cell responses were boosted in 75% of primed individuals.

Conclusions

These results demonstrate that HIV-1 protein immunogens can elicit durable memory T- and B-cell responses and that strong tier 1 virus neutralizing responses can be elicited by a single booster dose of protein following a long immunologic rest period. However, we found no evidence that cross-clade boosting led to a significantly broadened neutralizing antibody response.
The Location of Hosted Asylum Seekers in OECD Regions and Cities
Authors: Proietti Paola , Veneri Paolo
Published: January 2019

This document provides a comparative assessment on the location of hosted asylum seekers in 18 European countries at the level of TL3 regions and in six countries at the municipal level. The assessment is based on an ad-hoc data collection from national statistical offices and governmental agencies in charge of monitoring the hosting of asylum seekers. The analysis aims to maximize data comparability across countries by focusing on those asylum seekers who are hosted in the reception system. Results show that, on average, asylum seekers are less concentrated in urban areas than the resident population. This result is robust at different geographical scales, namely at the scale of small administrative regions (OECD TL3), at that of functional urban areas—a comparable definition of cities applied to OECD countries—and at the municipal level. In the subset of countries where information was available, the share of asylum seekers in rural areas has on average increased between 2011 and 2015. The dispersal measures implemented in several of the countries considered might have played a role in this respect.
‘These Curly-Bearded, Olive-Skinned Warriors’: Medicine, Prosthetics, Rehabilitation and the Disabled Sepoy in the First World War, 1914–1920
Authors: Nair Aparna
Published: January 2019

The sepoy had always been a central figure in colonial governance and policing and had played important roles in both world wars. Focusing on World War I, this article explores the sepoys’ corporeal experience of the war through their own letters. The article explores how the war had a catalytic impact on colonial perceptions of and responses to disability in the colony and how medicine, prosthetics and rehabilitation came to be seen as the ‘promise’ made by the Crown to Indian soldiers for their service. The article also examines the introduction of cultures and institutions of rehabilitation into the colony in the form of the Queen Mary Technical Institute and explores the intersections of race, empire and disability at these sites of rehabilitation.
Neutrophil activation in occupational asthma
Authors: Choi Youngwoo , Lee Youngsoo , Park Hae-Sim
Published: January 2019

Purpose of review

The aim of this review is to emphasize the role of neutrophils in patients with occupational asthma. This review facilitates a better understanding, accurate diagnosis, and proper management of asthmatic reactions provoked at the workplace.

Recent findings

Increased recruitment and infiltration of neutrophils are found in patients with occupational asthma. Activated neutrophils release several mediators including pro-inflammatory cytokines and extracellular traps, leading to stimulation of airway epithelium and other inflammatory cells.

New insights into neutrophils in the pathogenesis of occupational asthma may provide a novel approach to the individual patient with occupational asthma.
One Small Step for Step 1
Authors: Andolsek Kathryn M.
Published: January 2019

Step 1 of the United States Medical Licensing Examination (USMLE) is a multiple-choice exam primarily measuring knowledge about foundational sciences and organ systems. The test was psychometrically designed as pass/fail for licensing boards to decide whether physician candidates meet minimum standards they deem necessary to obtain the medical licensure necessary to practice. With an increasing number of applicants to review, Step 1 scores are commonly used by residency program directors to screen applicants, even though the exam was not intended for this purpose. Elsewhere in this issue, Chen and colleagues describe the “Step 1 climate” that has evolved in undergraduate medical education, affecting learning, diversity, and well-being.

Addressing issues related to Step 1 is a challenge. Various stakeholders frequently spend more time demonizing one another rather than listening, addressing what lies under their respective control, and working collaboratively toward better long-term solutions. In this Invited Commentary, the author suggests how different constituencies can act now to improve this situation while aspirational future solutions are developed.

One suggestion is to report Step 1 and Step 2 Clinical Knowledge scores as pass/fail and Step 2 Clinical Skills scores numerically. Any changes must be carefully implemented in a way that is mindful of the kind of unintended consequences that have befallen Step 1. The upcoming invitational conference on USMLE scoring (InCUS) will bring together representatives from all stakeholders. Until there is large-scale reform, all stakeholders should commit to taking (at least) one small step toward fixing Step 1 today.
Effect of Tuberosity Healing on Clinical Outcomes in Elderly Patients Treated With a Reverse Shoulder Arthroplasty for 3- and 4-Part Proximal Humerus Fractures
Authors: Simovitch Ryan W. , Roche Chris P. , Jones Richard B. , Routman Howard D. , Marczuk Yann , Wright Thomas W. , Zuckerman Joseph D.
Published: January 2019

Objectives:

To evaluate tuberosity union rate and clinical outcome after 3- and 4-part proximal humerus fractures in the elderly.

Design:

Retrospective, multicenter database cohort study.

Setting:

Level I and Level II trauma centers.

Patients:

Fifty-five patients older than 65 years had insertion of reverse shoulder arthroplasty (RTSA) for OTA/AO 11-B and 11-C proximal humerus fractures.

Intervention:

Treatment with RTSA using a dedicated low profile onlay fracture stem using variable tuberosity fixation.

Main Outcome Measures:

Constant score, the American Shoulder and Elbow Surgeons score, Shoulder Pain and Disability Index score, University of California at Los Angeles score, Simple Shoulder Test score, visual analog pain score, shoulder function score, active range of motion, external rotation (ER)-specific tasks and position, rate of greater tuberosity healing, effect of tuberosity healing on overall clinical metrics, incidence of humeral lucency, and scapular notching.

Results:

Eighty-three percent of the greater tuberosities that were repaired united. Greater tuberosity union resulted in greater active ER (P = 0.0415). There was a statistically significant difference in the ability to do ER-type activities between the 2 cohorts reflected in the ability to position one's hand behind their head with the elbow forward (P = 0.002) and comb their hair (P < 0.001).

Conclusion:

The use of a low profile onlay fracture stem in RTSA for acute 3- and 4-part proximal humerus fractures in the elderly can result in a high tuberosity union rate. Greater tuberosity healing significantly influences ER and ER-type activities that are not apparent by analysis of the overall metrics studied.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Psychiatric Illness Is Common in Elderly Fracture Patients
Authors: Gitajn Ida L. , Titus Alexander , Mastrangelo Sand , Ali Shuaibu , Sparks Michael , Jevsevar David
Published: January 2019

Objectives:

To (1) describe the prevalence of psychiatric illness in fracture patients ≥70 years of age and (2) investigate the association between psychiatric illness and complications requiring unplanned readmission in elderly patients.

Design:

Retrospective cohort study.

Patients/participants:

One thousand one hundred eighty-six patients ≥70 years of age with surgically treated fractures and ≥1-month follow-up treated from 2012 to 2017.

Intervention:

None.

Main outcome measure:

Complication requiring unplanned readmission.

Results:

Forty-four percent of patients ≥70 years of age have psychiatric comorbidities, and of those, 34% had >1 diagnosis. There was a higher rate of readmission among patients with psychiatric diagnosis compared with those without psychiatric diagnosis (35% vs. 21%, P < 0.001). There was a higher prevalence of psychiatric illness among patients 70 years of age or older compared with patients less than 70 years of age (44% vs. 39%, P = 0.007). Multivariate regression analysis controlling for age, sex, Charlson Comorbidity Index, dementia, delirium during admission, tobacco use, substance abuse, Injury Severity Score, fracture location, number of procedures, and number of fractures demonstrated an independent association between psychiatric illness and unplanned readmission (adjusted OR 1.54, 95% confidence interval, 1.15–2.07, P = 0.003).

Conclusions:

Almost half of the elderly patients in the present cohort have psychiatric comorbidities. Furthermore, psychiatric illness is an independent predictor of unplanned readmission, which may have substantial consequences for recovery and cost of care. This emphasizes the need for more attention to these issues in geriatric patient populations and the need to identify means to influence the downstream consequences of these comorbidities.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Dysglycemia and Neurologic Outcome in Mechanically Ventilated Patients With Guillain-Barré Syndrome
Authors: Polito Andrea , Polito Angelo , Bouchereau Eléonore , Moneger Guy , Ritzenthaler Thomas , Annane Djillali , Heming Nicholas , Sharshar Tarek
Published: January 2019

Objectives:

Acute respiratory failure is a frequent complication of Guillain-Barré syndrome, associated with high morbidity and mortality. Adjuvant treatments are needed to improve the outcome of Guillain-Barré syndrome. Since dysglycemia is a risk factor for development of axonal polyneuropathy in critically ill patients and since insulin therapy may be neuroprotective, we sought to explore the association between dysglycemia and neurologic status in Guillain-Barré syndrome patients.

Design:

Retrospective study.

Setting:

Single-center study.

Interventions:

All plasma levels of glycemia measured by enzymatic technique as well as capillary glycemia were collected in a cohort of mechanically ventilated Guillain-Barré syndrome patients. Insulin administration and dysglycemia were correlated to neurologic status at discharge defined by disability grade and arm grade.

Measurements and Main Results:

In a multivariate analysis, disability grade and arm grade at ICU discharge were independently and inversely correlated with mean blood glucose. Disability grade and arm grade did not correlate with any other dysglycemic variables or with insulin administration or length of stay.

Conclusions:

In the present study, we found that neurologic disability at ICU discharge correlated with dysglycemia in mechanically ventilated Guillain-Barré syndrome patients. These finding indicates that dysglycemia may delay motor recovery and impact the functional outcome of Guillain-Barré syndrome. Blood glucose control might be an adjuvant therapy for improving Guillain-Barré syndrome recovery.
Anterior decompression and fusion versus laminoplasty for cervical myelopathy due to ossification of posterior longitudinal ligament
Authors: Chen Tao-ping , Qian Li-gang , Jiao Jian-bao , Li Qing-gui , Sun Bo , Chen Kang , Wang Yun-fei , Liang Zhi-xing , Chen Yu-min , Meng Jie
Published: January 2019

Background:

Both anterior decompression and fusion (ADF) and laminoplasty (LAMP) are frequently used for the treatment of cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL). However, some controversies still remained in surgical options. We investigated whether ADF had better neurological outcome than LAMP in the treatment of cervical myelopathy due to OPLL. Secondary outcomes included operation time, blood loss, rate of complication and reoperation.

Methods:

PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for treatment of cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Quality assessment was performed according to Cochrane Handbook and meta-analysis was conducted using Stata 12.0 software.

Results:

Nine studies involving 712 patients were finally included in this analysis. Compared with LAMP, ADF was associated with an increase of the Japanese Orthopaedic Association (JOA) score (WMD = 1.86, 95% CI 0.43 to 3.29, P = .011) and recovery JOA score at final follow-up (WMD = 30.94, 95% CI 20.56 to 41.33, P = .000). And, ADF was associated with a decrease of the late neurologic deterioration than LAMP group (RR = 0.34, 95% CI 0.12 to 0.92, P = .003). However, ADF was associated with an increase of the postoperative cervical lordosis (WMD = 4.47, 95% CI 1.58 to 7.36, P = .002) than LAMP. There was no significant difference between the complication, reoperation rate (P > .05). What's more, ADF was associated with an increase of the operation time than LAMP (P < .05).

Conclusions:

ADF yields better neurological improvement, but higher cervical lordosis and longer operation time compared with LAMP for cervical myelopathy caused by OPLL. No significant difference was found in the complication and re-operation rate.
Apatinib monotherapy for advanced VEGFR-2-negative nasopharyngeal carcinoma
Authors: Jin Jun , Du Jiahao , Wu Yanwei
Published: January 2019

Rationale:

Due to the anatomical and biological characteristics of nasopharyngeal carcinoma (NPC), radiotherapy is the standard treatment of choice. Recent advances in small molecule therapies targeting tumor angiogenesis also hold promise for the treatment of advanced NPC.

Patient concerns:

The patient's symptoms, including nasal obstruction, nasal bleeding, and headache, reappeared periodically and eventually became so severe that the patient's vision became impaired. In January 2016, the patient presented with blurred vision, diplopia, language impairment, left temporal paralysis, and bilateral eyelid ptosis.

Diagnosis:

Advanced NPC without metastasis in a 55-year-old man.

Interventions:

The patient refused treatment with radiotherapy or chemotherapy and was treated with Chinese herbal medicines. Following a worsening of symptoms, the patient was subsequently treated with apatinib monotherapy (0.25 g, once daily).

Outcomes:

Symptom improvement, including decreased nasal bleeding and headache, was observed after 1 week of apatinib treatment. After 100 days of treatment, the patient was nearly asymptomatic with stable disease and improved quality of life.

Lessons:

For patients with advanced NPC who refuse standard radiotherapy and chemotherapy, apatinib monotherapy may be a suitable treatment option to improve symptoms and quality of life even in those with vascular endothelial growth factor receptor-negative tumors.
Case report: Staphylococcus aureus endocarditis in 2 premature newborns
Authors: Duperril Marie , Rapin Stéphanie , Vuillard Cécilia , Rayet Isabelle , Patural hugues
Published: January 2019

Rationale:

Neonatal infectious endocarditis (IE) in a healthy heart is rare. The infectious agents most frequently found in newborns are Staphylococcus aureus and fungi. Infection at the site of central intravenous catheter is generally thought to be the cause of this pathology.

Patient concerns:

We present 2 cases of premature newborns whose condition is evolving positively. They presented S aureus endocarditis during their first week of life.

Diagnosis:

Modified Duke diagnostic criteria—from clinical, echocardiogram and microbiological findings—based on those used for adults, can be used for children and newborns, but the very low prevalence of neonatal IE often delays diagnosis. Diagnosis on the basis of transthoracic heart ultrasound requires an extension report, given the very high embolic risk. Intervention: In the large majority of cases, long-term antibiotic therapy efficaciously treats the infection, although sometimes surgery is necessary. These 2 newborns needed only antibiotic therapy.

Outcome:

Despite the various complications, especially embolic, these 2 children are followed and are doing well.

Lessons:

Long-term pediatric heart monitoring combined with prophylactic antibiotics are essential, according to the European Society of Cardiology guidelines.
Simplified MIPI-B prognostic stratification method can predict the outcome well—retrospective analysis of clinical characteristics and management of newly-diagnosed mantle cell lymphoma patients from China
Authors: He Jing-Song , Chen Xi , Wei Guo-Qing , Sun Jie , Zheng Wei-Yan , Shi Ji-Min , Wu Wen-Jun , Zhao Yi , Zheng Gao-Feng , Huang He , Cai Zhen
Published: January 2019

Mantle cell lymphoma (MCL) is an invasive B-cell lymphoma with significant individual differences. Currently, MCL international prognostic index (MIPI) score and tumor cell proliferation index Ki-67 have been proved to be the most important prognostic factors. But the prognostic effect of these factors in Asian population is uncertain. This study aimed to analyze the disease characteristics and prognostic factors of Chinese MCL patients.

A total of 83 cases of newly-diagnosed MCL patients diagnosed by the Department of Pathology of our hospital between January 1, 2011, and May 31, 2016, were enrolled. The disease characteristics, treatment effects, and outcomes of the patients were collected and analyzed.

According to our analysis, MCL cases accounted for 6.2% of non-Hodgkin lymphoma (NHL) cases and mainly occurred in elderly males. But the proportion of patients at stage IV by Ann Arbor staging system and high-risk group by simplified-MIPI (s-MIPI) were significantly lower than that among European patients. Immunochemotherapy containing rituximab was significantly more effective than chemotherapy (overall response rate, [ORR]: 88.5% vs 65.2%, P = .021) and significantly prolonged patient survival (progression free survival [PFS]: 45.5 m vs 16.2 m, P = .001; overall survival [OS]: 58.3 m vs 22.8 m, P = .001). The multivariate analysis showed that the B symptoms, s-MIPI and administration of immunochemotherapy were independent prognostic factors that affected PFS and OS of the patients. s-MIPI and B symptom make up s-MIPI-B stratification method, by which patients in low-risk group of s-MIPI without B symptom were classified as low-risk, patients in high-risk group of s-MIPI and patients in low-risk group of s-MIPI with B symptom as high-risk, the rest as middle-risk. 3-year PFS of the 3 groups were 74.9%, 43.4% and 16.1%, respectively (P = .001). 3-year OS were 84.4%, 62.2%, 27.6% (P <.001).

Chinese MCL was male predominance. We have a minor proportion of late-stage and high-risk patients compared to European patients. Immunochemotherapy was proved to significantly improve the prognosis of MCL patients. B symptoms, s-MIPI, and administration of rituximab independently influenced the outcome. s-MIPI-B prognostic stratification method may better predict the prognosis of Asian MCL patients. Still, further confirmation in larger populations is needed.
PITX2 methylation: a novel and effective biomarker for monitoring biochemical recurrence risk of prostate cancer
Authors: Jiang Qi , Xie Mixue , He Mengye , Yan Feifei , Chen Ming , Xu Suzhen , Zhang Xiaochen , Shen Peng
Published: January 2019

Aims:

Prostate cancer is one of the most common malignancies in men. Biochemical recurrence (BCR) and progression following curative treatment pose a significant public health challenge. Thus, it is essential to explore effective biomarkers for disease progression monitoring and risk stratification. The promoter region of the paired-like homeodomain transcription factor 2 (PITX2) gene has been found to be frequently methylated in prostate cancer. However, the prognostic role of PITX2 methylation in prostate cancer and which patients most likely to be recommended for PITX2 methylation tests to assess BCR risk remain controversial. Therefore, a systematic review was performed to explore the relationship of PITX2 methylation with the BCR risk of prostate cancer.

Methods:

The PubMed, EMBASE, and Cochrane Library databases were systematically searched for eligible studies. Seven studies with a total of 2185 patients were included. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated.

Results:

The overall HR was 2.71 (95% CI, 2.21–3.31), suggesting that PITX2 methylation has an adverse impact on BCR of prostate cancer. The pooled estimate of 5-year BCR-free survival for patients with a high methylation status was significantly lower than that for patients with a low methylation status (71% vs 90%; odds ratio [OR] = 3.50; 95% CI, 2.67–4.60, P = .000). A subgroup analysis was conducted according to detection method; the combined HRs were 2.68 (95% CI, 2.02–3.55) for quantitative methylation-specific PCR (qMSP) and 3.29 (95% CI, 2.31–4.68) for microarray EpiChip. In subgroups defined by region, Gleason score, pathological stage, surgical margin status and ethnicity, high methylation status was also associated with BCR of prostate cancer.

Conclusions:

As an effective biomarker, PITX2 methylation is feasible for individualized BCR risk assessment of prostate cancer following radical prostatectomy.
Risk factors for failure of hydrostatic reduction of intussusception in pediatric patients
Authors: Xiaolong Xie , Yang Wu , Qi Wang , Yiyang Zhao , Bo Xiang
Published: January 2019

The aim of this current study was to explore the risk factors associated with failure of hydrostatic reduction of intussusception in pediatric patients.

Patients with intussusception treated with hydrostatic reduction from January 2010 to December 2016 were retrospectively analyzed. Candidates for inclusion in the study were children from 0 to 18 who were diagnosed with intussusception and treated with hydrostatic reduction. We excluded the patients who had contraindications for hydrostatic reduction, which included peritonitis, perforation signs, and non-responsive shock that required surgery. The data collected included: demographic data (sex, age, and bodyweight), symptoms (vomiting, abdominal pain, rectal bleeding, diarrhea, distention, constipation, and duration of symptoms), signs (temperature, palpable mass, and location of the mass), and other investigations (white blood cell counts, neutrophils, electrolytes, and ultrasound findings).

The risk factors for failure of hydrostatic reduction of intussusception were analyzed using the univariable analysis and the multivariable analysis. In the univariable model, the significant risk factors for failure of hydrostatic reduction of intussusception analyzed were age, bodyweight, duration of symptoms, rectal bleeding, constipation, palpable abdominal mass, poor prognosis signs on ultrasound scans and location of mass (the P value for each parameter are stated in Table 1

JOURNAL/medi/04.03/00005792-201901040-00016/table1/v/2023-09-14T035325Z/r/image-tiff

). After the multivariable analysis was done, we found that the significant risk factors for failure of hydrostatic reduction of intussusception were an age of under 1-year-old (OR = 3.915, P = .027), duration of symptoms more than or equal to 48 h (OR = 0.056, P < .001), rectal bleeding (OR = 0.283, P = .003), constipation (OR = 0.086, P < .001), palpable abdominal mass (OR = 0.370, P = .010), and location of mass (left over right side) (OR = 13.782, P < .001).

Our study found that an age of under 1-year-old, a duration of symptoms of more than or equal to 48 h, rectal bleeding, constipation, palpable abdominal mass and location of mass (left over right side) were risk factors for the failure of hydrostatic reduction of intussusception.
X-linked dominant chondrodysplasia punctata with severe phenotype in a female fetus
Authors: Liu Yan , Wang Li , Xu Bin , Yang Yike , Shan Dan , Wu Qingqing
Published: January 2019

Rationale:

X-linked dominant chondrodysplasia punctata type 2 (CDPX2) is a condition involving facial, skin, and skeletal dysplasia as a result of a mutation in emopamil binding protein (EBP). It usually presents with mild symptoms in female patients but is fatal in male patients.

Patient concerns:

A fetus was diagnosed with asymmetrical short limbs and a narrow and small thorax by prenatal ultrasound examination at 24+5 weeks gestation. The pregnancy was terminated at 27 weeks of gestation; gross examination, postnatal X-ray and, whole exome analysis were performed to clarify the diagnosis.

Diagnosis:

A provisional diagnosis of fatal skeletal dysplasia was given and the definite diagnosis of CDPX2 was based on postnatal X-ray and genetic testing of the aborted fetus.

Intervention:

The pregnancy was terminated at 27 weeks’ gestation after a fetal ultrasound indicated a severe abnormal phenotype.

Outcomes:

Whole exome analysis of aborted tissue confirmed EBP mutation in this case. Unlike most case reports, this female patient presented a severe phenotype that was considered to be related to X-chromosome inactivation.

Lessons:

Chondrodysplasia punctata (CDP) should be considered if prenatal ultrasound shows high punctuate echoes at the metaphysis of long bones and asymmetrical short lower limbs. Postnatal X-ray and measurement of sterol levels in the amniotic fluid may aid in the diagnosis of CDP, but the condition can be confirmed with genetic testing of a blood sample or aborted tissue after delivery.
Application of computer simulation in the treatment of traumatic cubitus varus deformity in children
Authors: Jiang Hai , Li Min , Wu Yongtao
Published: January 2019

Cubitus varus deformity is common in children. The purpose of this study was to assess the usefulness of computer simulation based on three-dimensional computed tomography (3D-CT) reconstruction with regard to preoperative planning and surgical treatment in children with traumatic cubitus varus deformity.

The study included 13 patients with traumatic cubitus varus deformity between January 2012 and January 2015. The original 3D-CT data were transferred to Mimics 10.01 software. Special tools were used for simulation of supracondylar lateral wedge osteotomy of the humerus. Intraoperative elbow arthrography was used to identify the articular surface of the elbow joint for assisting the judgment of the osteotomy site. Kirschner wires were used to determine the osteotomy plane and angle. The osteotomy site was fixed by crossing Kirschner wires and steel wire tension band.

Of the 13 patients, 11 were male and 2 were female. The left side was affected in 8 patients, and the right side was affected in 5 patients. The patient age ranged from 2 years to 14 years (mean age, 6 years and 7 months). The varus angle ranged from 12° to 35° (mean angle, 20°). The carrying angle on the contralateral side ranged from 5° to 18° (mean angle, 10°). The varus deformities showed good correction. The 13 patients were followed up for 24 to 60 months (mean follow-up, 38 months). According to the Flynn score of elbow joint function after surgery: 10 patients had excellent function, 2 had good function, and 1 had fair function. The excellent rate was 92.3%. At the final follow-up, the ipsilateral carrying angle ranged from 4° to 15° (mean angle, 11°).

Computer simulation based on 3D-CT reconstruction can provide good information on the right humeral osteotomy position and osteotomy angle. It can guide the actual operation and provide better results after surgery. Intraoperative elbow arthrography is useful to determine the level of elbow joint osteotomy, and it can assist in the operation.

Level of evidence: Level IV-retrospective case, treatment study.
A randomized controlled trial of ultrasound-guided pulsed radiofrequency for patients with frozen shoulder
Authors: Yan Juan , Zhang Xian-min
Published: January 2019

Background:

This study assessed the effectiveness and safety of ultrasound-guided pulsed radiofrequency (UGPRF) for patients with frozen shoulder (FS).

Methods:

This study was designed as a randomized, double-blind, sham control trial. A total of 136 patients with FS were recruited and then were equally randomly allocated into a treatment group (n = 68) and a sham group (n = 68). The patients in the treatment group received UGPRF, while the subjects in the sham group underwent sham UGPRF. Patients in both groups were treated for a total of 12 weeks. The primary outcome was the pain intensity, measured by the visual analog scale (VAS). The secondary outcomes consisted of shoulder disorder, measured by the score of shoulder pain and disability index (SPADI); quality of life, assessed by the Short Form-36 questionnaire (SF-36); and any adverse events (AEs) during the treatment period. All outcomes were measured at baseline, at the end of 6-week, and 12-week treatment.

Results:

At the end of 6 weeks, and 12 weeks, UGPRF showed more promising outcome results in pain relief, as measured by VAS (P <.01), improvement of shoulder disorder, as assessed by SPADI score (pain, P <.01; disability, P <.01; total, P <.01), and enhancement of quality of life, as measured by the SF-36 scale (PCS, P <.01; MCS, P <.01), compared with sham UGPRF in this study.

Conclusion:

The findings of this study showed that UGPRF may benefit for patients with FS after 12 weeks treatment.
Microsatellite instability and manifestations of angiogenesis in stage IV of sporadic colorectal carcinoma
Authors: Otto Włodzimierz , Macrae Finlay , Sierdziński Janusz , Smaga Justyna , Król Maria , Wilińska Ewa , Zieniewicz Krzysztof
Published: January 2019

Angiogenesis represents one of the critical mechanisms that facilitates carcinoma development. The study objective was to evaluate whether the microsatellite instability of colorectal carcinoma has impact on the angiogenesis activity in liver metastases.

In a cohort of 80 randomly selected patients with stage IV colorectal carcinoma, 30% were recognized as microsatellite unstable (Microsatellite instability high-frequency (MSI-H)). The endothelial progenitor cell fraction (CD309+) was counted within the subpopulation of CD34+CD45+ cell and CD34+CD45- cells by flow cytometer. vascular endothelial growth factor (VEGF) factor levels were quantified in serum samples by enzyme-linked immunosorbent assay (ELISA). A control group consisted of 36 healthy volunteers. The relationship of genomic instability to angiogenesis activity was evaluated by multivariate analysis in comparison to the controls, adopting a P < .05 value as statistically significant.

The expression of endothelial progenitor cells (EPCs) and VEGF was significantly higher in MSI-H compared to both microsatellite stability (MSS) patients and healthy controls (P < .008). Multi-parametric analysis showed microsatellite instability (OR=9.12, P < .01), metastases in both lobes (OR = 32.83, P < .001) and simultaneous metastases outside liver (OR = 8.32, P < .01), as independent factors associated with increased angiogenesis as assessed by measures of EPC and VEGF. A higher percentage of EPCs within the white blood cell fraction (total % EPCs / white blood cells (WBC)) and higher serum concentrations of VEGF were present in patients with MSI-H colorectal cancer, and not with MSS cancers (P < .001).

MSI-H patients with colorectal cancer metastases are associated with the overexpression of circulating EPCs and VEGF, potentially driving angiogenesis. This should be considered in therapeutic decision-making.
Congenital internal carotid artery hypoplasia
Authors: Hou Dianbin , Mei Yu , Ji Yongqiang , Wu Hongliang , Zhang Huilong , Sun Zhongwen , Li Wenjuan , Li Bing , Ren Chao , Guan Lina , Liu Chuanyu
Published: January 2019

Rationale:

Congenital internal carotid artery hypoplasia (CICAH) is rarely reported. This study aimed to discuss the epidemiological characteristics, clinical manifestation, imaging and treatment of CICAH.

Patient concerns:

The case was male who showed barylalia and limited abilities of the left limbs as their main clinical manifestation. This patient was diagnosed CICAH by digital subtraction angiography (DSA) and computed tomography (CT).

Diagnosis:

CICAH.

Interventions:

The patient underwent anti platelet aggregation, lipid-lowering, improving cerebral circulation.

Outcomes:

The patient was in a stable condition after management of cerebrovascular risk.

Lessons:

Given the asymptomatic and congenital nature of carotid agenesis, no treatment is necessary or possible to re-establish the internal carotid artery (ICA). However, with the high risk of aneurysm and cerebrovascular insufficiency, management of cerebrovascular risk is important. Urgent radiological assessment is necessary for patients with suspicious neurological symptoms.
Comorbidity is associated with higher risk of financial burden in Medicare beneficiaries with cancer but not heart disease or diabetes
Authors: Jones Salene M.W. , Chennupati Shasank , Nguyen Trung , Fedorenko Catherine , Ramsey Scott D.
Published: January 2019

The aim of the study was to examine how multimorbidity influences the prevalence of financial burden among older adults with heart disease, diabetes, or cancer.

The study was a cross-sectional analysis of prospective observational cohort survey study.

Older adults (age 65 or older) who did not report 1/6 major chronic illnesses (n = 2773; reference group), reported 1/3 major chronic illnesses without comorbidity (heart disease n = 206; diabetes n = 460; cancer n = 417), and reported 1/3 major chronic illnesses with comorbidity (heart disease n = 232; diabetes n = 202; cancer n = 109).

The measures were presence of chronic diseases (heart disease, diabetes, cancer), comorbid chronic diseases (stroke, lung disease, dementia), medical-related financial burden (credit card debt due to medical costs, paying medical bills over time), and overall financial burden (financial help from family, credit card debt, help with food, utilities, and other necessities).

The proportion reporting financial burden ranged from 15% to 27% across samples. Heart disease was unrelated to medical or overall financial burden, regardless of comorbidity. Diabetes was unrelated to financial burden except diabetes without comorbidity was associated with lower odds of overall financial burden compared to healthy older adults (odds ratio [OR] = 0.655, 95% confidence interval [CI]: 0.468–0.917). Cancer with comorbidity, but not cancer without comorbidity, was associated with greater odds of medical related (OR = 1.678, 95% CI: 1.057–2.664) and overall financial burden (OR = 1.748, 95% CI: 1.064–2.872).

The association of multimorbidity with financial burden likely varies based on specific diseases. Future research on financial burden should focus on specific disease combinations such as cancer with comorbidity.
Novel EZH2 mutation in a patient with secondary B-cell acute lymphocytic leukemia after deletion 5q myelodysplastic syndrome treated with lenalidomide
Authors: Burgos Sebastian , Montalban-Bravo Guillermo , Fuente Lucia , Jabbour Elias J. , Kanagal-Shamanna Rashmi , Soltysiak Kelly A. , Garcia-Manero Guillermo , Mela-Osorio Maria J.
Published: January 2019

Rationale:

The gene deletion (5)(q22q35) is reported in 10–20% of myelodysplastic syndrome (MDS) cases and is associated with response to lenalidomide and favorable prognosis. The authors report here a clinical case of MDS transformation to B-cell acute lymphocytic leukemia (B-ALL) with an associated accrual of an additional mutation following treatment with lenalidomide.

Patient Concerns:

A 69-year-old man presented with progressive anemia, normal white blood cell count, and thrombocytopenia consistent with MDS. He was administered lenalidomide for 27 months, then developed acute B-cell lymphocytic leukemia and acquired a previously unreported mutation in the gene enhancer of zeste homolog 2 (EZH2).

Diagnoses:

After 27 months of therapy with lenalidomide, a surveillance bone marrow aspiration (BMA) revealed 90% cellularity with persistent multilineage dysplasia and a population of blasts comprising 54% of all bone marrow elements by morphology, consistent with B-ALL, even though the patient was asymptomatic. Conventional karyotype showed no signs of del(5)(q22q35) MDS, however bone marrow next–generation sequencing (NGS) demonstrated the accrual of a nonsense mutation (c.211del pL71∗) in exon 3 of EZH2. A confirmatory BMA yielded 70% blasts and clinical features indicative of B-ALL.

Interventions:

Mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 × 4 doses) was administered for 21 days.

Outcomes:

A follow-up BMA was performed 2 months after mini-hyper-CVD therapy, showing dysplastic features with 25% ring sideroblasts, but no evidence of B-ALL. The patient is currently receiving monthly-low dose decitabine, ofatumumab, and dexamethasone, and is transfusion independent and asymptomatic after 7 cycles.

Lessons:

The present study shows an extremely rare progression of del(5)(q22q35) MDS to B-ALL with accompanying NGS data and a newly described acquisition of an EZH2 frameshift mutation. This case highlights the importance of NGS as a diagnostic and surveillance tool for MDS.