bluuebunny/crossref_metadata_2025 huggingface dataset:
High lipoprotein(a) and high risk of mortality
Authors: Langsted Anne , Kamstrup Pia R , Nordestgaard Børge G
Published: December 2018

Aims

Several lipoprotein(a)-lowering therapies are currently being developed with the long-term goal of reducing cardiovascular disease and mortality; however, the relationship between lipoprotein(a) and mortality is unclear. We tested the hypothesis that lipoprotein(a) levels are associated with risk of mortality.

Methods and results

We studied individuals from two prospective studies of the Danish general population, of which 69 764 had information on lipoprotein(a) concentrations, 98 810 on LPA kringle-IV type 2 (KIV-2) number of repeats, and 119 094 on LPA rs10455872 genotype. Observationally, lipoprotein(a) >93 mg/dL (199 nmol/L; 96th–100th percentiles) vs. <10 mg/dL (18 nmol/L; 1st–50th percentiles) were associated with a hazard ratio of 1.50 (95% confidence interval 1.28–1.76) for cardiovascular mortality and of 1.20 (1.10–1.30) for all-cause mortality. The median survival for individuals with lipoprotein(a) >93 mg/dL (199 nmol/L; 96th–100th percentiles) and ≤93 mg/dL (199 nmol/L; 1st–95th percentiles) were 83.9 and 85.1 years (log rank P = 0.005). For cardiovascular mortality, a 50 mg/dL (105 nmol/L) increase in lipoprotein(a) levels was associated observationally with a hazard ratio of 1.16 (1.09–1.23), and genetically with risk ratios of 1.23 (1.08–1.41) based on LPA KIV2 and of 0.98 (0.88–1.09) based on LPA rs10455872. For all-cause mortality, corresponding values were 1.05 (1.01–1.09), 1.10 (1.04–1.18), and 0.97 (0.92–1.02), respectively. Finally, for a similar cholesterol content increase, lipoprotein(a) was more strongly associated with cardiovascular and all-cause mortality than low-density lipoprotein, implying that the mortality effect of high lipoprotein(a) is above that explained by its cholesterol content.

Conclusion

High levels of lipoprotein(a), through corresponding low LPA KIV-2 number of repeats rather than through high cholesterol content were associated with high risk of mortality. These findings are novel.
State evolution for approximate message passing with non-separable functions
Authors: Berthier Raphaël , Montanari Andrea , Nguyen Phan-Minh
Published: December 2018

Given a high-dimensional data matrix $\boldsymbol{A}\in{{\mathbb{R}}}^{m\times n}$, approximate message passing (AMP) algorithms construct sequences of vectors $\boldsymbol{u}^{t}\in{{\mathbb{R}}}^{n}$, ${\boldsymbol v}^{t}\in{{\mathbb{R}}}^{m}$, indexed by $t\in \{0,1,2\dots \}$ by iteratively applying $\boldsymbol{A}$ or $\boldsymbol{A}^{{\textsf T}}$ and suitable nonlinear functions, which depend on the specific application. Special instances of this approach have been developed—among other applications—for compressed sensing reconstruction, robust regression, Bayesian estimation, low-rank matrix recovery, phase retrieval and community detection in graphs. For certain classes of random matrices $\boldsymbol{A}$, AMP admits an asymptotically exact description in the high-dimensional limit $m,n\to \infty $, which goes under the name of state evolution. Earlier work established state evolution for separable nonlinearities (under certain regularity conditions). Nevertheless, empirical work demonstrated several important applications that require non-separable functions. In this paper we generalize state evolution to Lipschitz continuous non-separable nonlinearities, for Gaussian matrices $\boldsymbol{A}$. Our proof makes use of Bolthausen’s conditioning technique along with several approximation arguments. In particular, we introduce a modified algorithm (called LoAMP for Long AMP), which is of independent interest.
Variation in Morphology and Kinematics Underlies Variation in Swimming Stability and Turning Performance in Freshwater Turtles
Authors: Mayerl C J , Youngblood J P , Rivera G , Vance J T , Blob R W
Published: December 2018

Among swimming animals, stable body designs often sacrifice performance in turning, and high turning performance may entail costs in stability. However, some rigid-bodied animals appear capable of both high stability and turning performance during swimming by propelling themselves with independently controlled structures that generate mutually opposing forces. Because such species have traditionally been studied in isolation, little is known about how variation within rigid-bodied designs might influence swimming performance. Turtles are a lineage of rigid-bodied animals, in which most species use contralateral limbs and mutually opposing forces to swim. We tested the stability and turning performance of two species of turtles, the pleurodire Emydura subglobosa and the cryptodire Chrysemys picta. Emydura subglobosa exhibited both greater stability and turning performance than C. picta, potentially through the use of subequally-sized (and larger) propulsive structures, faster limb movements, and decreased limb excursions. These data show how, within a given body design, combinations of different traits can serve as mechanisms to improve aspects of performance with competing functional demands.
Two kinematically distinct old globular cluster populations in the Large Magellanic Cloud
Authors: Piatti Andrés E , Alfaro Emilio J , Cantat-Gaudin Tristan
Published: December 2018

We report results of proper motions of 15 known Large Magellanic Cloud (LMC) old globular clusters (GCs) derived from the Gaia DR2 data sets. When these mean proper motions are gathered with existent radial velocity measurements to compose the GCs’ velocity vectors, we found that the projection of the velocity vectors on to the LMC plane and those perpendicular to it tells us about two distinct kinematic GC populations. Such a distinction becomes clear if the GCs are split at a perpendicular velocity of 10 km s−1 (absolute value). The two different kinematic groups also exhibit different spatial distributions. Those with smaller vertical velocities are a part of the LMC disc, while those with larger values are closely distributed like a spherical component. Since GCs in both kinematic–structural components share similar ages and metallicities, we speculate with the possibility that their origins could have occurred through a fast collapse that formed halo and disc concurrently.
Hyperglycemia and Risk of All-cause Mortality Among People Living With HIV With and Without Tuberculosis Disease in Myanmar (2011–2017)
Authors: Kyaw Nang Thu Thu , Satyanarayana Srinath , Oo Htun Nyunt , Kumar Ajay M V , Harries Anthony D , Aung Si Thu , Kyaw Khine Wut Yee , Phyo Khaing Hnin , Aung Thet Ko , Magee Matthew J
Published: December 2018

Background

There is limited empirical evidence on the relationship between hyperglycemia, tuberculosis (TB) comorbidity, and mortality in the context of HIV. We assessed whether hyperglycemia at enrollment in HIV care was associated with increased risk of all-cause mortality and whether this relationship was different among patients with and without TB disease.

Methods

We conducted a retrospective analysis of adult (≥15 years) HIV-positive patients enrolled into HIV care between 2011 and 2016 who had random blood glucose (RBG) measurements at enrollment. We used hazards regression to estimate associations between RBG and rate of all-cause mortality.

Results

Of 25 851 patients, 43% were female, and the median age was 36 years. At registration, the median CD4 count (interquartile range [IQR]) was 162 (68–310) cell/mm3, the median RBG level (IQR) was 88 (75–106) mg/dL, and 6.2% (95% confidence interval [CI], 6.0%–6.5%) had hyperglycemia (RBG ≥140 mg/dL). Overall 29% of patients had TB disease, and 15% died during the study period. The adjusted hazard of death among patients with hyperglycemia was significantly higher (adjusted hazard ratio [aHR], 1.2; 95% CI, 1.1–1.4) than among those with normoglycemia without TB disease, but not among patients with TB disease (aHR, 1.0; 95% CI, 0.8–1.2). Using 4 categories of RBG and restricted cubic spline regression, aHRs for death were significantly increased in patients with RBG of 110–140 mg/dL (categorical model: aHR, 1.3; 95% CI, 1.2–1.4; restricted spline: aHR, 1.1; 95% CI, 1.0–1.1) compared with those with RBG <110 mg/dL.

Conclusions

Our findings highlight an urgent need to evaluate hyperglycemia screening and diagnostic algorithms and to ultimately establish glycemic targets for PLHIV with and without TB disease.
Factors and outcomes associated with paediatric emergency department arrival patterns through the day
Authors: Almubarak Hathami , Meckler Garth , Doan Quynh
Published: December 2018

Introduction

Steadily increasing emergency department (ED) utilization has prompted efforts to increase resource allocation to meet demand. Little is known about the distribution and characteristics of patient arrivals by time of day. This study describes the variability and patterns of ED resource utilization related to patient, acuity, clinical, and disposition characteristics over a 24-hour period.

Methods

Retrospective cross-sectional study of all visits to a tertiary children’s hospital over a 1-year period. We use descriptive statistics to present ED visit details stratified by shift of arrival, and multivariable regression to explore the association between shift of presentation and hospital admission at index and 7-day return ED visits.

Results

Of 46,942 visits during the study period, 12% arrived overnight, 42% during the day, and 45% during the evening with variability in pattern of shift arrival by day of week. Overnight arrivals had a higher acuity (Canadian Triage and Acuity Scale [CTAS]) and different presenting complaints (more viral infection, less minor trauma) than day and evening arrivals, but similar ED length of stay. Shift of arrival was not associated with admission to hospital, but age, gender, socioeconomic status (SES), and day of week were.

Discussion

ED utilization patterns vary by shift of arrival. Though overnight arrivals represent a smaller proportion of total daily arrivals, their acuity is higher, and the spectrum of disease differs from day or evening arrivals.

Conclusions

Understanding variations and patterns of ED utilization by shift of arrival and day of week may be helpful in tailoring resource allocation to more accurately and specifically meet demands.
Reboxetine and hyoscine butylbromide improve upper airway function during nonrapid eye movement and suppress rapid eye movement sleep in healthy individuals
Authors: Lim Richard , Carberry Jayne C , Wellman Andrew , Grunstein Ron , Eckert Danny J
Published: December 2018

Study Objectives

Recent findings indicate that noradrenergic and antimuscarinic processes are crucial for sleep-related reductions in pharyngeal muscle activity. However, there are few human studies. Accordingly, this study aimed to determine if a combined noradrenergic and antimuscarinic intervention increases pharyngeal dilator muscle activity and improves airway function in sleeping humans.

Methods

Genioglossus (GG) and tensor palatini electromyography (EMG), pharyngeal pressure, upper airway resistance, and breathing parameters were acquired in 10 healthy adults (5 female) during two overnight sleep studies after 4 mg of reboxetine (REB) plus 20 mg of hyoscine butylbromide (HBB) or placebo using a double-blind, placebo-controlled, randomized, cross-over design.

Results

Compared with placebo, peak and tonic GG EMG were lower (Mean ± SD: 83 ± 73 vs. 130 ± 75, p = 0.021 and 102 ± 102 vs. 147 ± 123 % wakefulness, p = 0.021, respectively) but the sleep-related reduction in tensor palatini was less (Median [25th, 75th centiles]: 53[45, 62] vs. 34[28, 38] % wakefulness, p = 0.008) with the drug combination during nonrapid eye movement (non-REM) sleep. These changes were accompanied by improved upper airway function including reduced pharyngeal pressure swings, airway resistance, respiratory load compensation, and increased breathing frequency during N2. REB and HBB significantly reduced rapid eye movement sleep compared with placebo (0.6 ± 1.1 vs. 14.5 ± 6.8 % total sleep time, p < 0.001).

Conclusions

Contrary to our hypothesis, GG muscle activity (% wakefulness) during non-REM sleep was lower with REB and HBB. However, sleep-related reductions in tensor palatini activity were less and upper airway function improved. These findings provide mechanistic insight into the role of noradrenergic and antimuscarinic processes on upper airway function in humans and have therapeutic potential for obstructive sleep apnea.

Clinical Trial Registration

Australian New Zealand Clinical Trials Registry, https://www.anzctr.org.au, trial ID: ACTRN12616000469415.
Invasive molecular prenatal diagnosis of alpha and beta thalassemia among Hakka pregnant women
Authors: Wu Heming , Wang Huaxian , Lan Liubing , Zeng Mei , Guo Wei , Zheng Zhiyuan , Zhu Huichao , Wu Jie , Zhao Pingsen
Published: December 2018

This study is a retrospective analysis of the prenatal genetic diagnosis results of fetuses with high risk of major thalassemia to provide information for clinical genetic counseling and to better control the birth of major thalassemia child in Hakka population. Totally, 467 fetuses in at-risk pregnancies were collected from Meizhou people's hospital from January 2014 to December 2017. Genomic DNAs were extracted from peripheral blood of the couples and villus, amniotic fluid or cord blood of the fetuses. DNA-based diagnosis was performed using polymerase chain reaction (PCR) and flow-through hybridization technique. Follow-up visits were done half a year after the fetuses were born. Around 467 fetus at-risk pregnancies were performed prenatal diagnosis. We detected 88 CVS samples, 375 amniocentesis fluid samples and, 4 cord blood samples. The 356 fetuses in α-thalassemia families consisted of 69 (19.38%) with Bart's hydrops syndrome, 20 (5.62%) fetuses with Hb H disease, and 184 (51.68%) fetuses with heterozygote. And the 111 fetuses in β-thalassemia families consisted of 31 (27.93%) thalassemia major, 51 (45.95%) fetuses with heterozygote. There are 13 fetuses with α+β-thalassemia, including 2 cases with severe β-thalassemia. DNA-based testing prenatal diagnosis of thalassemia was found to be highly reliable. Our findings provide key information for clinical genetic counseling of prenatal diagnosis for major thalassemia in Hakka pregnant women. Our work plays an important role in the prevention and control of thalassemia in Hakka population. We will also combine other techniques to further improve our molecular prenatal diagnostic capabilities, including the next-generation sequencing (NGS), Sanger sequencing and MLPA.
Multiple myeloma with crystal-storing histiocytosis, crystalline podocytopathy, and light chain proximal tubulopathy, revealed by retinal abnormalities
Authors: Boudhabhay Idris , Titah Chérif , Talbot Alexis , Harel Stéphanie , Verine Jérôme , Touchard Guy , Kaaki Sihem , Gabison Eric , Vasseur Vivien , Mauget-Faÿsse Martine , Sené Thomas
Published: December 2018

Rationale:

Crystal sorting histiocytosis (CSH) is a rare disorder that is morphologically characterized by the accumulation of monoclonal immunoglobulin crystals, predominantly of a kappa light chain type, within lysosomes of macrophages. CSH may result in a variety of clinical manifestations depending on the involved organs. In this case report, we aim to describe a patient with ophthalmic manifestations which lead to the diagnosis of multiple myeloma with crystal-storing histiocytosis, crystalline podocytopathy, and light chain proximal tubulopathy.

Patient concerns:

A 60-year-old male patient presented with progressive bilateral decreased vision for 2 years.

Diagnosis:

Ophthalmic explorations showed bilateral macular and papillary edema, and multiple crystalline deposits in the anterior stromal cornea and in the retina. Laboratory tests showed nephrotic syndrome and renal dysfunction. Further work-up revealed IgG kappa multiple myeloma, with biopsy-proven combined crystalline podocytopathy and tubulopathy.

Interventions:

The patient received chemotherapy (bortezomib, cyclophosphamide, and dexamethasone for 3 cycles, then bortezomib, lenalidomide, and dexamethasone).

Outcomes:

Despite partial hematologic response and improvement of the papilledema and macular edema, the patient developed dialysis-dependent end-stage renal failure.

Lessons:

This report, highlighting the protean presentation of paraprotein-mediated injuries, provides additional information on the ocular anomalies not previously described that may be associated with crystal-storing histiocytosis.
Population genetic difference of pharmacogenomic VIP gene variants in the Lisu population from Yunnan Province
Authors: Zhang Chan , Jiang Xiaochun , Chen Wanlu , Li Qi , Yun Fubin , Yang Xin , Dai Run , Cheng Yujing
Published: December 2018

Individual differences in drug clinical response are related to pharmacogenomics. The genetic variation of drug-metabolizing enzymes, drug receptors, and their downstream protein genes is the main factor causing individual differences in drug response. The genetic backgrounds among different ethnic groups are quite different. In this study, we aimed to detect the distribution difference of genotype frequency in very important pharmacogenetic (VIP) gene variants in the Lisu.

Using the chi-squared test, we compared the genotype frequencies of the VIP variants in 105 Lisu people with those in 26 populations from the 1000 Genome project separately. Bonferroni's multiple adjustment was also conducted (P < .05/(26∗49)). Moreover, Arlequin v3.5 and Structure v2.3.4 software were used to analyze the genetic distance and genetic structure.

There were 9, 9, 11, 12, 11, 11, 9, 17, 13, 13, 16, 5, 3, 5, 3, 4, 17, 14, 16, 17, 16, 10, 13, 12, 10, and 9 single nucleotide polymorphisms that differed in frequency distribution, when Lisu people compared with the 26 populations separately. Only CYP2E1 rs2070676 was different in the Lisu population compared with the 26 groups from the 1000 Genome project. PTGS2 rs5275 and CYP2D6 rs1065852 were different in the Lisu population compared with most of the populations. Additionally, genetic backgrounds of Lisu and Han Chinese in Beijing were closest according to the lowest F-statistics value and resemblance in genetic structures.

Our results complete the information of the Lisu population in pharmacogenomics database.
Increased risk of appendectomy in patients with gastroesophageal reflux disease
Authors: Kim So Young , Kim Hyung-Jong , Lim Hyun , Lim Man Sup , Kim Miyoung , Choi Hyo Geun
Published: December 2018

The purpose of this study is to confirm and complement previous data regarding an association between gastroesophageal reflux disease and appendectomy.

The Korean National Health Insurance Service-National Sample Cohort includes data from people ≥ 20 years old collected from 2002 to 2013. A total of 13,484 participants who received an appendectomy were matched with 53,936 controls at a 1:4 ratio. We analyzed the previous histories of gastroesophageal reflux disease (GERD) in the appendectomy and control groups. Appendectomies were identified using operation codes (Q2860-Q2863) exclusive for appendicitis (International Classification of Disease-10 (ICD-10): K35). GERD was defined using the ICD-10 (K21), and patients who were treated ≥ 2 times and were prescribed a proton pump inhibitor (PPI) for ≥ 2 weeks were included. Crude (simple) and adjusted odds ratios (ORs) for GERD and appendectomy were analyzed using conditional logistic regression analyses.

A higher GERD rate was detected in the appendectomy group (11.4% [1,713/15,062]) than in the control group (8.2% [4,947/60,248], P < .001). Adjusted ORs for GERD were 1.37 (95% confidence interval [CI] = 1.30–1.45) (P < .001). Subgroup analyses stratified according to age and sex revealed consistent findings. The adjusted OR for GERD in participants prescribed PPIs for ≥ 30 days was 1.31 (95% CI = 1.20–1.43), and the adjusted OR for GERD in participants prescribed PPIs for ≥ 60 days was 1.30 (95% CI = 1.15–1.48).

The Odds for GERD were higher in the appendectomy group than in the control group.
Prolonged neuromuscular block associated with cholinesterase deficiency
Authors: Zhang Chao , Cao Hui , Wan Zhi Gang , Wang Jie
Published: December 2018

Rationale:

Hereditary genetic mutations may cause congenital cholinesterase deficiency. When succinylcholine and mivacurium are applied on cholinesterase-deficient patients during general anesthesia, prolonged postoperative asphyxia occurs, which is an uncommon but very serious complication.

Patient concerns:

A previously healthy 30-year-old female presented prolonged spontaneous breathing recovery after general anesthesia.

Diagnoses:

After the patient's postoperative spontaneous breathing recovery delayed, the plasma cholinesterase was found to be 27 U/L, which was far below the normal level (4000 U/L to 13500 U/L). This patient had no disease that can cause plasma cholinesterase deficiency and was therefore diagnosed as congenital cholinesterase deficiency.

Interventions and outcomes:

The patient was sent to the intensive care unit (ICU) intubated for mechanical ventilator support, and on the next day the tracheal tube was removed without any complications when her spontaneous respiration resumed.

Lessons:

Cholinesterase is an enzyme secreted by the liver involved in many physiological processes in human body. Plasma cholinesterase commonly contains acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). When succinylcholine and mivacurium are applied on patients with cholinesterase-deficiency during general anesthesia, prolonged postoperative asphyxia occurs, which is an uncommon but very serious complication. Lately, new evidences have suggested that hereditary genetic mutations may be responsible for congenital cholinesterase deficiency.
The clinical outcome of recurrent sacral chordoma with further surgical treatment
Authors: Yang Yongkun , Li Yuan , Liu Weifeng , Xu Hairong , Niu Xiaohui
Published: December 2018

Case series.

To analyze the clinical results and related factors of further surgical treatment for recurrent sacral chordomas.

Chordomas are rare primary malignant tumors with a high recurrence rate. The treatment of recurrent tumors is difficult and controversial. Contamination by previous operations and disturbed local anatomical structures may increase the risk of reoperation. Most previous studies have focused on the primary tumor; there are very few reports on the clinical diagnosis, treatment, and prognosis of recurrent sacral chordomas.

Thirty-four patients with recurrent sacral chordomas from 1979 to 2014 were included in this study. The patients comprised 25 men and 9 women with an average age of 50.7 (24–75) years. The average time until recurrence was 19.4 (4–51) months postoperatively, and 85.3% of the recurrent tumors were located in bone. The patients had an average of 1.2 (1–3) recurrences before further operations were performed in our hospital. The mean maximum tumor diameter was 8.1 (4.6–12.0) cm. Thirty-one patients underwent further tumor resection in our hospital. The postoperative recurrence, metastasis, and survival results were followed and analyzed.

The mean follow-up after surgical treatment of recurrence was 49.6 (12–144) months. Nine patients (37.5%) developed recurrence again after an average of 26.7 months. The 3-year and 5-year recurrence-free survival rate was 69.4% and 63.1%, respectively. Multivariate analysis showed that the tumor level within the sacrum (P = .001) and the surgical margin (P = .001) were significant recurrence-related factors. Four patients (16.7%) developed lung metastasis. Eighteen patients were alive at last follow-up. The 5-year and 10-year survival rate after surgical treatment of recurrence was 67.3% and 53.9%, respectively.

Most recurrent tumors are located in bone, and a safe osteotomy margin is important. The surgical margin is the only controllable factor of further tumor recurrence. Some patients with recurrence achieve long survival and obtain a clinical benefit from repeated operations if complete resection is achieved.
Traditional Chinese medicine classic herbal formula Xiaoqinglong decoction for acute exacerbation of chronic obstructive pulmonary disease
Authors: Zhen Gao , Jing Jing , Fengsen Li
Published: December 2018

Background:

Xiaoqinglong decoction (XQLD) is 1 of the traditional Chinese medicine (TCM) classic herbal formula that is widely used in Asian for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). In recent years, there has been increasing interest in the use of XQLD to treat COPD in China. So it is necessary to update the research and re-evaluate the efficacy and safety of XQLD to provide up-to-date evidence for COPD management. Therefore, we provide a protocol for a systematic review of XQLD for COPD. This protocol is described for a systematic review to investigate the beneficial effects and safety of XQLD for AECOPD.

Methods:

A systematic literature search for article up to October 2018 will be performed in 3 Chinese electronic databases and 2 English electronic databases: Pubmed, Cochrane library, China national knowledge infrastructure (CNKI), Chinese science and technology periodical database (VIP), and Wanfang database. Inclusion criteria are randomized control trials of XQLD in treating AECOPD. The primary outcomes were total clinical efficacy rate, TCM symptom scores, TCM Symptom relief time. The secondary outcome was lung function, blood gas analysis, inflammatory cytokines and C-reactive protein (CRP). The summary results will be pooled using the random-effects model or fixed-effects model according to the heterogeneity of the included studies.

Result:

This systematic review will provide an evidence of XQLD for AECOPD, and will submit to a peer-reviewed journal for publication.

Conclusion:

The conclusion of this systematic review will provide evidence to judge whether XQLD is an effective intervention for AECOPD patients.
Imaging features of spinal atypical teratoid rhabdoid tumors in children
Authors: Wu Hui-Ying , Xu Wen-Biao , Lu Lian-Wei , Li He-Hong , Tian Jin-Sheng , Li Jian-Ming , Chen Zheng-Rong
Published: December 2018

This study aims to analyze and summarize the imaging features of spinal atypical teratoid/rhabdoid tumors (AT/RT) in children.

Imaging features in 8 children with spinal AT/RT confirmed by surgical pathology were retrospectively analyzed. All patients had underwent total spine 3.0 T magnetic resonance imaging (MRI) and 64-slice spiral computed tomography (CT). Among these 8 patients, head MR non-enhanced and spinal enhanced scanning was applied to 5 patients, while CT examination was applied to 3 patients.

All 8 patients were characterized by cauda equina syndrome. The lesions of 7 patients were in the thoracolumbar spinal junction, while the lesion of the remaining patient was in the lumbar spine. Furthermore, among these patients, the lesions of 5 patients were limited to the intraspinal canal (1 lesion in the epidural space, and 4 lesions in the subdural space), while the lesions of 3 patients invaded the paravertebra (2 lesions in the epidural space and 1 lesion in the subdural space). Three or more spinal segments were invaded by tumors in 7 patients, while sacral canal was affected in 5 patients. All 8 patients experienced bleeding in the tumors. Enhanced MRI revealed meningeal enhancement in 6 patients, and bilateral nerve root enhancement in 4 patients. The masses in 3 patients brought damages to the intervertebral foramen or sacral pore. The lesion of 1 patient was featured by skip growth. One patient had total spinal metastasis and 3 had hydrocephalus. The masses in 2 patients had a slightly low density when detected by CT, and enhanced scanning revealed a mild to moderate enhancement.

Spinal AR/TR had the following characteristics: children were characterized by cauda equina syndrome; the mass that invaded the thoracolumbar spinal junction and the extramedullary space of multiple segments grew along the spinal longitudinal axis; bleeding mass was revealed in MRI imaging; meninges, nerve root, and sacral canal metastases occurred. The gold standard for the definite diagnosis of AT/RT is biopsy combined with immunohistochemistry.
Vitiligo-like lesions in a patient treated with nivolumab for renal cell carcinoma
Authors: Lolli Cristian , Medri Matelda , Ricci Michela , Schepisi Giuseppe , Filograna Alessia , De Giorgi Ugo , Stanganelli Ignazio
Published: December 2018

Rationale:

The introduction of immune check-point inhibitors (ICIs) in the treatment of solid neoplasms is associated with the need to know and manage a new type of side effects that are commonly defined immune-mediated adverse events. Dermatologic immune-mediated adverse events are relatively common. Vitiligo-like lesions, defined as hypopigmented skin lesions, have already been associated with the use of ICIs in particular in patients with malignant melanoma, probably due to a common autoimmune mechanism against both melanoma cells and normal melanocytes. The onset of vitiligo-like lesions is very rare in non-melanoma patients and nowadays only few cases are described in the literature.

Patient concerns:

We described the case of a heavily pre-treated woman affected by renal cell carcinoma that has been treated with nivolumab for 2 years obtaining a stabilization of disease after an initial mild progression. After 9 months from the beginning of nivolumab, when the disease has reached its maximum stabilization, the patient developed vitiligo-like lesions of the back win halo nevi.

Diagnoses:

Vitiligo like lesion of the back not pre-existing before nivolumab treatment. The etiology was assumed to be nivolumab related as a result of an autoimmune activation against normal melanocytes.

Interventions:

The patient was followed with dermatological evaluations without changes in nivolumab dose and schedule

Outcomes:

No variations of the described lesions were recorded after the first description. The patients underwent a durable stabilization of her tumor.

Lessons:

This case on the one hand is the first case of vitiligo-like lesions associated with ICIs in patients affected by renal cell carcinoma, and on the other hand it seems to confirm that the onset of immumomediate adverse reactions, but in particular vitiligo lesions, can probably be considered a sign of response to immunological treatments probably as a consequence of activation of the immune response.
Self-perceived limitations and difficulties by Primary Health Care Physicians to assist emergencies
Authors: Cernuda Martínez José Antonio , Castro Delgado Rafael , Arcos González Pedro
Published: December 2018

The study was aimed to identify the training received in Emergency Medicine by physicians and the limitations and difficulties self-perceived by those physicians to assist in emergencies, as well as to analyze the differences according to the work context.

Observational cross-sectional study made by a survey using a self-administered questionnaire to a representative simple random sample (with replacement) of 294 doctors (n) working at the Primary Health Care centers out of the total of 851 doctors (N) that form the staff of physicians of Primary Health Care system of Asturias (Spain).

In rural areas, the most frequently mentioned reasons were the lack of practical skills (32.65%), absence of adequate material (20.41%), lack of theoretical knowledge (8.16%), and poor equipment conditions (4.08%). In the semi-urban area, the most common reasons were the lack of practical skills (19.61%), lack of theoretical knowledge (10.78%), absence of adequate material (8.82%), and poor equipment conditions (4.90%). Finally, in the urban area, the main reason was the lack of practical skills (23.40%), absence of adequate material (20.21%), lack of theoretical knowledge (9.57%), and poor equipment conditions (4.26%). The differences were significant (P = .003) among the 3 work context.

The absence of practical skills is the most frequent cause referred by doctors of the 3 areas as a key to not act correctly in an emergency. The doctors of the rural area perceive that they are better prepared in general to solve emergencies and it is the professionals of 3 areas that report having carried out more basic cardiopulmonary resuscitation, advanced and attention to the polytraumatized patient courses.
Altered brain volume and its relationship to characteristics of carotid plaques in asymptomatic patients
Authors: Tuo Jia , Liu Yunhai , Liao Weihua , Gu Wenping , Yang Shuai , Tan Xinglin , Tang Tao , Chen Hua , Feng Jie , Wen Yanbin , He Wei , Huang Qing
Published: December 2018

Carotid plaque is an aggregate marker of exposure to vascular risk factors, which are linked to structural brain changes. We investigated prestroke global and regional changes in brain volume in a carotid plaque population of cognitively healthy individuals and the association between carotid plaque characteristics and these changes.

A total of 76 participants were divided into healthy control (HC, n = 28), vulnerable plaque (n = 27) and stable plaque groups (n = 21). All subjects underwent carotid ultrasound and brain magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) was used to examine differences in regional gray matter volumes (rGMVs) among the different groups.

The plaque group had a significantly lower mean total cerebral brain volume (TCBV) than the HC group (P = .03). Carotid intima-media thickness (CIMT) was negatively correlated with TCBV (r = -0.311, P = .006) and rGMV in the right thalamus (r = -0.589, P = .001). The rGMVs of the right middle occipital gyrus and bilateral lingual gyrus were significantly different between the unstable and stable groups. The gray-scale median (GSM) of the plaque and the total plaque risk score (TPRS) were correlated with the volume of the right middle occipital gyrus (r=-0.478, P = .001; r = 0.541, P = .001) and bilateral lingual gyrus (r = -0.419, P = .003; r = 0.288, P = .04).

Carotid plaque is related to the volume of the brain parenchyma and right thalamus. The rGMVs of the right middle occipital gyrus and bilateral lingual gyrus differed between the vulnerable plaque and stable plaque groups, and the characteristics of carotid plaques may serve as indexes that reflect these changes
Traditional Chinese medicine for post-stroke depression
Authors: Huang Wanlin , Liao Xiaoqin , Tian Jinhui , Wu Jing , Shan Yawei , Zhou Weini
Published: December 2018

Background:

Post-stroke depression (PSD) is common in stroke survivors, with significantly negative effects and serious impairments in terms of personal and social functioning. While both pharmacological and traditional Chinese medicine (TCM) interventions have been administered for PSD, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank, describing the protocol of a systematic review and network meta-analysis (NMA), the commonly used TCM interventions for PSD.

Methods and analysis:

We will search CENTRAL (the Cochrane Central Register of Controlled Trials), CINAHL, Embase, PubMed, CBM and PsycINFO, the US National Institutes of Health and the World Health Organisation International Trials Registry Platform search portal from inception to November 2018. There will be no restrictions on language, publication year or publication type. Only randomized clinical trials (RCTs) accessing any TCM treatments against active comparator or other controls for PSD will be included. The primary outcomes will be efficacy (the total number of participants, declining more than 50% on the total score between baseline) and acceptability of treatment (dropout rate due to any cause). A Bayesian NMA will be performed to compare all relative outcome of different TCM interventions. we will conduct the network meta-regression meta-analyses of data on the sex ratio, the types of stroke and the treatment duration of TCM interventions. Potential explanations in extra subgroup analyses according to the results of heterogeneity and inconsistency will be explored, and sensitivity analyses will be conducted to assess the robustness of the findings.

Trials registration number:

PROSPERO CRD42018082400.

Conclusion:

Our study will generate evidence for TCM in the treatment of PSD and help to reduce the uncertainty about the effectiveness of PSD management, which will encourage further suggestions for TCM clinical practice or guideline.
Transcutaneous auricular vagus nerve stimulation in treating major depressive disorder
Authors: Wu Chunxiao , Liu Peihui , Fu Huaili , Chen Wentao , Cui Shaoyang , Lu Liming , Tang Chunzhi
Published: December 2018

Background:

Transcutaneous auricular vagus nerve stimulation (taVNS), as a noninvasive intervention, has beneficial effects on major depressive disorder based on clinical observations. However, the potential benefits and clinical role of taVNS in the treatment of major depressive disorder are still uncertain and have not been systematically evaluated. Therefore, we performed a systematic review and meta-analysis to evaluate the effectiveness and safety of taVNS in treating major depressive disorder.

Methods:

Four electronic databases, namely, Embase, MEDLINE, the Cochrane Library and PsycINFO, were searched for all related trials published through May 1, 2018. We extracted the basic information and data of the included studies and evaluated the methodological quality with the Cochrane risk of bias tool and the nonrandomized studies-of interventions (ROBINS-I) tool. A meta-analysis of the comparative effects was conducted using the Review Manager 5.3 software.

Results:

A total of 423 citations from the databases were searched, and 4 studies with 222 individuals were included in the meta-analysis. The taVNS technique could decrease 24-item HAMD scores more than the sham intervention (MD: −4.23, 95% CI: −7.15, −1.31; P = .005) and was also more effective in decreasing Self-Rating Depression Scale scores ((MD: −10.34, 95% CI: −13.48, −7.20; P < .00001), Beck Depression Inventory scores (MD: −10.3, 95% CI: −18.1, −2.5; P = .01) and Self-Rating Anxiety Scale scores (MD: −6.57, 95% CI: −9.30, −3.84; P < .00001). However, there was no significant difference in the Hamilton Anxiety Rating Scale scores between the taVNS and sham taVNS groups (MD: −1.12, 95% CI: −2.56, 0.32; P = .13). No obvious adverse effects of taVNS treatment were reported in the included studies.

Conclusion:

The results of the analysis preliminarily demonstrated that taVNS therapy can effectively ameliorate the symptoms of major depressive disorder, providing an alternative technique for addressing depression. However, more well-designed RCTs with larger sample sizes and follow-ups are needed in future studies to confirm our findings.
Modified grade 4 osteotomy for kyphosis due to old osteoporotic vertebral compression fractures
Authors: Liu Feng-Yu , Zhao Zheng-Qi , Ren Liang , Gu Zhen-Fang , Li Feng , Ding Wen-Yuan , Sun Xian-Ze
Published: December 2018

Rationale:

The kyphosis caused by old osteoporotic vertebral compression fracture usually requires osteotomy to correct it. Various osteotomy techniques have been reported, but each has its own advantages and disadvantages.

Patient concerns:

We reviewed 2 cases of old osteoporotic vertebral compression fractures with kyphosis in our hospital. One patient complained of persistent low-back pain, another patient complained of low-back pain and weakness of both lower extremities.

Diagnosis:

Old osteoporotic vertebral compression fractures with kyphosis were diagnosed based on computer tomography and magnetic resonance imaging.

Interventions:

We performed modified grade 4 osteotomy for 2 patients.

Outcomes:

Both patients said significant improvement in preoperative symptoms, and x-ray showed that the kyphosis was corrected. Both patients were satisfied with the treatment at the last follow-up, and the kyphosis was not aggravated.

Lessons:

Modified grade 4 osteotomy is an effective option for the treatment of old osteoporotic fracture with kyphosis. It can restore the spine sequence and achieve better clinical result.
Ectopic relapse of IgG4-related disease presenting as IgG4-related sclerosing cholecystitis
Authors: Ishigami Keisuke , Shitani Masahiro , Kimura Yasutoshi , Hasegawa Tadashi , Masaki Yoshiharu , Ito Ayako , Akutsu Noriyuki , Yamamoto Motohisa , Motoya Masayo , Sasaki Shigeru , Takahashi Hiroki , Takemasa Ichiro , Nakase Hiroshi
Published: December 2018

Rationale:

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a chronic inflammatory disorder characterized by high levels of serum IgG4, swollen organs with fibrosis and abundant infiltration of IgG4-positive plasmacytes.

Patient Concerns:

An 82-year-old male visited our hospital for an evaluation of a pancreatic enlargement and a bilateral submandibular adenopathy. Further investigation revealed elevation of serum IgG4 and bilateral lacrimal submandibular adenopathy. We diagnosed him with IgG4-related disease (IgG4-RD) and started administration of corticosteroid (CS) therapy. Both pancreatic enlargement and adenopathy rapidly improved; however, there was a new occurrence of diffuse wall thickening of the gallbladder during CS treatment.

Diagnosis:

Radiological examination revealed diffuse wall thickening of the gallbladder, and its inner layer was smooth and homogenous. These findings suggested an inflammatory change, but the possibility of malignancy could not be excluded.

Interventions:

The patient underwent laparoscopic cholecystectomy for a pathological diagnosis.

Outcomes:

Histological examination revealed a transmural infiltration of IgG4 positive plasma cells and dense fibrosis. The patient was pathologically diagnosed with IgG4 related cholecystitis presenting as an ectopic relapse.

Lessons:

There are 2 major types of IgG4-related cholecystitis, a diffuse wall thickening type and a mass formation type. It is sometimes difficult to differentiate IgG4-related cholecystitis with gallbladder cancer.

Corticosteroid (CS) is effective for induction of remission; however, we sometimes encounter disease relapse after reduction of CS dose. We should be mindful that some patients may relapse with new organ involvements even if the primary site and serum IgG4 level are well controlled.
Pharmacologic interventions for preventing delirium in adult patients after cardiac surgery
Authors: Wen Junru , Zeng Hai , Li Zunjiang , He Guoxin , Jin Yueling
Published: December 2018

Background:

Delirium is common in adult patients undergoing cardiac surgery and related to a high morbidity and mortality. Although a variety of pharmacologic interventions have been applied in delirium prevention, there is still uncertainty concerning which drug is optimal. Thus, we plan to conduct a systematic review and network meta-analysis (NMA) of published studies to assess the efficacy and safety of pharmacologic interventions for preventing delirium among those patients.

Methods:

A systematic literature search will be conducted in Embase, PubMed, and the Cochrane Library. The primary outcome will be the incidence of postoperative delirium. Secondary outcomes will include all-cause mortality and length of hospital or intensive care unit stay. A frequentist NMA will be conducted using Stata version 14.0. The inconsistency between direct and indirect comparisons will be evaluated using a node splitting method. In addition, surface under the cumulative ranking area will be used to evaluate superiority of different treatments.

Results:

The findings of our review will be submitted to a peer-reviewed publication.

Conclusion:

Our study will generate convincing evidence regarding the effectiveness and safety of different pharmacologic interventions for delirium prevention in cardiac surgery patients.
Sine causa tetraparesis
Authors: Galli Jessica , Gavazzi Francesco , De Simone Micaela , Giliani Silvia , Garau Jessica , Valente Marialuisa , Vairo Donatella , Cattalini Marco , Mortilla Marzia , Andreoli (Laura , Badolato Raffaele , Bianchi Marika , Carabellese Nice , Cereda Cristina , Ferraro Rosalba , Facchetti Fabio , Fredi Micaela , Gualdi Giulio , Lorenzi Luisa , Meini Antonella , Orcesi Simona , Tincani Angela , Zanola Alessandra , Rice Gillian , Fazzi Elisa
Published: December 2018

Tetraparesis is usually due to cerebral palsy (CP), inborn errors of metabolism, neurogenetic disorders and spinal cord lesions. However, literature data reported that about 10% of children with tetraparesis show a negative/non-specific neuroradiological findings without a specific etiological cause. Aicardi Goutières Syndrome (AGS) is a genetic encephalopathy that may cause tetraparesis. Interferon signature is a reliable biomarker for AGS and could be performed in sine-causa tetraparesis. The aim of the study was to examine the type I interferon signature and AGS related-genes in children with sine causa tetraparesis, to look for misdiagnosed AGS. A secondary aim was to determine which aspects of the patient history, clinical picture and brain imaging best characterize tetraparesis due to an interferonopathy.

Seven out of 78 patients affected by tetraparesis, characterized by unremarkable pre-peri-postnatal history and normal/non-specific brain magnetic resonance imaging (MRI) were selected and underwent anamnestic data collection, clinical examination, brain imaging review, peripheral blood interferon signature and AGS-related genes analysis.

At our evaluation time (mean age of 11.9 years), all the 7 patients showed spastic-dystonic tetraparesis. At clinical onset brain MRI was normal in 4 and with non-specific abnormalities in 3; at follow-up 3 patients presented with new white-matter lesions, associated with brain calcification in 1 case. Interferon signature was elevated in one subject who presented also a mutation of the IFIH1 gene.

AGS should be considered in sine-causa tetraparesis. Core features of interferonopathy-related tetraparesis are: onset during first year of life, psychomotor regression with tetraparesis evolution, brain white-matter lesions with late calcifications. A positive interferon signature may be a helpful marker to select patients with spastic tetraparesis who should undergo genetic analysis for AGS.
Discrepancy between perfusion- and diffusion-weighted images in ischemic stroke
Authors: Hur Wook , Kim Bum Joon , Shin Byoung-Soo , Kang Hyun Goo
Published: December 2018

Rationale:

With the development of multi-slice computed tomography (CT) technology, perfusion CT angiography (p-CTA) is now widely used for the diagnosis of acute cerebral infarction. Although p-CTA has the advantage of distinguishing between an ischemic penumbra and an infarct core, more research is needed with respect to its clinical use.

Patient concerns:

A healthy 36-year-old man experienced sudden dizziness while swimming. His dizziness persisted irrespective of the change in position, and then improved during transport. He had no neurological abnormality when he arrived at the emergency room.

Diagnoses:

CT perfusion findings suggested left cerebellar infarction. P-CTA revealed a markedly delayed mean transit time, delayed time to peak, and increased cerebral blood volume in the left posterior inferior cerebellar artery territory at admission. However, the diffusion-weighted image (DWI) taken a few hours later revealed a large right cerebellar infarction.

Interventions:

Because of the time window, thrombolysis could not be performed and anti-platelet therapy was started.

Outcomes:

Dysarthria and right-sided limb ataxia were newly developed before DWI (after p-CTA). Persistent foramen ovale was detected through transesophageal echography and identified as the cause of the stroke.

Lessons:

This case report suggests that dynamic image changes can occur within a short period of time depending on the vascular status and hemodynamic changes of the patients.