2019年 · 第132卷第12期

Complex higher-risk and indicated patients (CHIPs) refers to patients with severe coronary artery disease (CAD) needing revascularization. However, these patients are at an increased risk for this procedure.^[1]The CHIP population is attracting much interest in the field of interventional cardiology, since it was introduced in 2016 by Kirtaneet al,^[1]and the optimal treatment strategies for this population were fiercely discussed in almost every interventional forum at home and abroad. First of all, a comprehensive risk assessment must be conducted to determine which patients with CAD should undergo revascularization based on clinical presentation, functional tests, and anatomic characteristics. Percutaneous coronary intervention (PCI) might be a beneficial option when complete revascularization can be achieved, especially for patients are either inoperable or at higher surgical risk.^[2,3]To treat these high-risk patients safely and effectively with PCI, well-trained interventionalists exhibiting both technical and cognitive skills are needed.

Mental stress-induced myocardial ischemia (MSIMI) is closely associated with adverse cardiac events in patients with coronary artery disease (CAD) and we aimed to determine whether biomarkers and blood pressure could be potential predictors of MSIMI.

This study enrolled 82 patients with documented CAD between June 1, 2017 and November 9, 2017. Patient blood samples were obtained at resting period and at the end of mental arithmetic. Then, patients were assigned to MSIMI positive group and MSIMI negative group. The main statistical methods included linear regression, receiver operating characteristic (ROC) curves, and logistic regression.

Patients with CAD with MSIMI had significantly greater median resting N-terminal pro-brain natriuretic peptide (NT-proBNP, 141.02 [45.85–202.76] pg/mL vs. 57.95 [27.06–117.64] pg/mL; Z = -2.23, P = 0.03) and mean systolic blood pressure (SBP) (145.56 ± 16.87 mmHg vs. 134.92 ± 18.16 mmHg, Z = -2.13, P = 0.04) when compared with those without MSIMI. After 5-min mental stress task, those who developed MSIMI presented higher elevation of median post-stressor high sensitivity cardiac troponin I (hs-cTnI, 0.020 [0.009–0.100] ng/mL vs. 0.009 [0.009–0.010] ng/mL; Z = -2.45, P = 0.01), post-stressor NT-proBNP (138.96 [39.93–201.56] pg/mL vs. 61.55 [25.66–86.50] pg/mL; Z = -2.15, P = 0.03) compared with those without MSIMI. Using the ROC curves, and after the adjustment for basic characteristics, the multiple logistic regression analysis showed that patients presenting a post-stressor hs-cTnI ≥ 0.015 ng/mL had seven-fold increase in the risk of developing MSIMI (odds ratio [OR]: 7.09; 95% confidence interval [CI]: 1.65–30.48; P = 0.009), a rest NT-proBNP ≥ 80.51 pg/mL had nearly eight-fold increase (OR: 7.85; 95% CI: 1.51–40.82; P = 0.014), a post-stressor NT-proBNP ≥ 98.80 pg/mL had 35-fold increase (OR: 34.96; 95% CI: 3.72– 328.50; P = 0.002), a rest SBP ≥ 129.50 mmHg had 11-fold increase (OR: 11.42; 95% CI: 1.21–108.17; P = 0.034).

The present study shows that CAD patients with higher hs-cTnI level, and/or greater NT-proBNP and/or SBP are at higher risk of suffering from MSIMI when compared with those without MSIMI, indicating that hs-cTnI, NT-proBNP, SBP might be potential predictors of MSIMI.

Necroptosis plays an important role in human atherosclerosis and atheroma development. Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis, this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity.

A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study. Patients with CAD were divided into three subgroups: patients with stable coronary artery disease (SCAD), patients with unstable angina (UA), and patients with myocardial infarction (MI). The severity of atherosclerosis was determined by Gensini score (GSS). Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD. The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models.

Overall, plasma RIP3 levels were significantly higher than serum RIP3 levels. Plasma RIP3 levels in patients with CAD were significantly higher than those in controls. Plasma RIP3 levels were strongly associated with CAD (odds ratio: 6.00, 95% confidence interval 3.04–11.81; P < 0.001). Plasma RIP3 levels increased linearly from controls to patients with SCAD, then patients with UA, and finally to patients with MI. We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile. Plasma RIP3 levels were also associated with GSS (B 0.027; standard error 0.012; P < 0.05).

Plasma RIP3 levels were independently associated with CAD. Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.

The long-term predicted value of microvolt T-wave alternans (MTWA) for ventricular tachyarrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains unclear. Our study explored the characteristics of MTWA and its prognostic value when combined with an electrophysiologic study (EPS) in patients with ARVC.

All patients underwent non-invasive MTWA examination with modified moving average (MMA) analysis and an EPS. A positive event was defined as the first occurrence of sudden cardiac death, documented sustained ventricular tachycardia (VT), ventricular fibrillation, or the administration of appropriate implantable cardioverter defibrillator therapy including shock or antitachycardia pacing.

Thirty-five patients with ARVC (age 38.6 ± 11.0 years; 28 males) with preserved left ventricular (LV) function were recruited. The maximal TWA value (MaxValt) was 17.0 (11.0–27.0) μV. Sustained VT was induced in 22 patients by the EPS. During a median follow-up of 99.9 ± 7.7 months, 15 patients had positive clinical events. When inducible VT was combined with the MaxValt, the area under the curve improved from 0.739 to 0.797. The receiver operating characteristic curve showed that a MaxValt of 23.5 μV was the optimal cutoff value to identify positive events. The multivariate Cox regression model for survival showed that MTWA (MaxValt, hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01–1.11; P = 0.01) and inducible VT (HR, 5.98; 95% CI, 1.33–26.8; P = 0.01) independently predicted positive events in patients with ARVC.

MTWA assessment with MMA analysis complemented by an EPS might provide improved prognostic ability in patients with ARVC with preserved LV function during long-term follow-up.

Perioperative and median-term follow-up outcomes have not been compared among procedures using radiofrequency ablation devices for permanent atrial fibrillation with concomitant rheumatic valve disease. We compared the sinus rhythm restoration efficacy of "non-irrigation" ablation forceps and an "irrigation" ablation device in patients with rheumatic valve disease undergoing a modified Cox maze radiofrequency ablation procedure due to permanent atrial fibrillation.

Data of 278 patients with rheumatic valve disease from the Cardiac Surgery Department of Sichuan Provincial People’s Hospital who underwent the modified Cox maze radiofrequency ablation procedure between May 2013 and May 2017 were reviewed. The procedure was performed using "non-irrigation" ablation forceps (AtriCure, group A) in 149 patients and an "irrigation" ablation device (Medtronic, group M) in 129 patients. Data were collected prospectively, and follow-up was documented and compared between the groups.

The radiofrequency procedure duration was 28.9 ± 3.8 min in group A and 29.5 ± 2.8 min in group M (t = 1.623, P = 0.106). The predicted radiofrequency time to the left atrium diameter was (Ya = 0.4964 X + 0.3762, R² = 0.74) in group A and (Ym = 0.4331 X + 4.3563, R² = 0.8435) in group M. The sinus rhythm (SR) conversion rate without use of anti-arrhythmic drugs was similarly good in groups A and M, with 75.2%, 72.5%, and 70.5% vs. 73.6%, 71.3%, and 69.8% at discharge, 6 and 12 months, respectively (F = 0.084, F = 0.046, F = 0.046, P > 0.05, respectively).

Two types of radiofrequency ablation devices characteristic of "non-irrigation" and "irrigation" bipolar ablation forceps were similarly efficient at SR restoration.

Youths are disproportionally affected by the human immunodeficiency virus (HIV) infection. We aimed to assess antiretroviral therapy (ART) initiation and viral suppression rates among student and non-student youths in Hangzhou, China.

Data were taken from the Chinese HIV/acquired immune deficiency syndrome Comprehensive Response Information Management System. Youths aged 15 to 24 years who were newly diagnosed with HIV between 2012 and 2016 and were living in Hangzhou were included in the study. Comparisons between student and non-student youths were made for ART initiation within 30 days, 90 days, and 12 months of HIV diagnosis, and the viral suppression rate at 12 months of HIV diagnosis and at 12 months of ART initiation.

A total of 707 cases met inclusion criteria, 29.6% of which were students and 70.4% were non-student youths. The student group had a higher proportion of ART initiation compared with the non-student group within 30 days of diagnosis (45.5% vs. 37.0%, P = 0.044), and a slightly higher but not statistically significant proportion at 90 days (67.0% vs. 62.7%), and 12 months (83.7% vs. 78.5%) of HIV diagnosis. ART initiation within 30 days improved from <15% in 2012 to over 65% in 2016 in both groups, and ART initiation within 90 days improved from <30% in 2012 to >90% in 2016. A smaller proportion of students experienced viral suppression compared with the non-student group (9.6% vs. 17.1%, P = 0.011) at 12 months after HIV diagnosis, but the suppression rate was similar at 12 months of ART initiation (69.9% vs. 71.1%, P = 0.743).

ART initiation in both student and non-student youths has significantly improved between 2012 and 2016. However, the viral suppression rate remained unacceptably low at 12 months of HIV diagnosis in both student and non-student groups. Specific intervention strategies must be taken to address this challenge.

Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is an important issue with significant morbidity and mortality in clinical practice, especially in diabetes mellitus (DM). Studies focusing on S. aureus pneumonia in DM is limited, we sought to make a relatively comprehensive exploration of clinical characteristics, antimicrobial resistance, and risk factors for mortality of S. aureus pneumonia in DM and non-diabetics mellitus (non-DM).

A retrospective study was conducted in Ruijin Hospital from 2014 to 2017. The characteristics of DM and non-DM patients were assessed, including demographics, comorbidities, using of invasive mechanical ventilation, Hemoglobin A1c (HbA1C), confusion, urea, respiratory rate, blood pressure, age ≥65 years (CURB-65) score, length of hospital stay, clinical outcomes, antimicrobial susceptibility. Independent risk factors for mortality were identified by univariate and multivariate logistic regression analysis.

A total of 365 patients with S. aureus pneumonia were included in our study, including 144 with DM and 221 non-DM. DM patients were more susceptible to MRSA infection (65.3% vs. 56.1%, P > 0.05), suffered from much severer pneumonia with a higher CURB-65 score, invasive mechanical ventilation rate (46.5% vs. 28.1%, P < 0.01) and mortality rates (30.6% vs. 23.1%, P > 0.05); almost all DM patients had higher antimicrobial resistance than non-DM patients, the DM group had a higher coinfection rate (47.2% vs. 45.7%, P > 0.05), and Acinetobacter baumannii was the most common bacterium in DM, while Klebsiella pneumoniae ranked first in patients with non-DM. Independent risk factors for pneumonia-related mortality were MRSA and CURB-65. Higher HbA1c levels were linked to a higher MRSA infection and co-infection rate and more severe pneumonia, leading to an increase in mortality.

DM patients with poor glucose control are more susceptible to MRSA infection. They suffer from higher antimicrobial resistance, a higher co-infection rate, and much severer pneumonia than non-DM. MRSA itself is an independent risk factor for mortality in all patients.

Previous studies have shown that endogenous T cells play an important role in the prolonged survival time of highgrade glioma (HGG) patients. Our objectives were to investigate the features of T-cell receptor (TCR) repertoires in HGG patients and to elucidate any potential therapeutic value.

During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing Tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). Then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in TCR beta chain (TRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data.

The Shannon diversity index (SHDI) of TRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). The SHDI of TRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t = -5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t = -2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of TRBV9 and TRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of TRBV4 and TRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic TCR sequence.

HGG patients have less species diversity of TCR repertoires compared with that of healthy individuals. TRBV9 regions in TCRs may be protective factors for long-term survival of GBM patients.

Diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. This study aimed to compare the diagnostic performance of HIT expert probability (HEP) and 4T scores, and to evaluate the inter-observer reliability for the 4T score in a clinical setting.

This prospective study included HIT-suspected patients between 2016 and 2018. Three hematologists assessed the HEP and 4T scores. Correlations between scores and anti-platelet factor 4 (anti-PF4)/heparin antibodies were evaluated. Receiver operating characteristic curves and area under the curve (AUC) were used to assess the predictive accuracy of these two scoring models. The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement of 4T scores between residents and hematologists.

Of the 89 subjects included, 22 (24.7%) were positive for anti-PF4/heparin antibody. The correlations between antibody titer and either HEP or 4T scores were similar (r = 0.392, P < 0.01 for the HEP score; r = 0.444, P < 0.01 for the 4T score). No significant difference in the diagnostic performance was displayed between these two scores (AUC for the HEP score: 0.778 vs. AUC for the 4T score: 0.741, P = 0.357). Only 72 4T scores were collected from the residents, with a surprisingly low percentage of observers (43.1%) presenting the four individual item scores which made up their 4T score. The AUC of 4T score assessed by residents and hematologists was 0.657 (95% confidence interval [CI]: 536–0.765) and 0.780 (95% CI: 0.667–0.869, P < 0.05), respectively. The ICC of 4T score between residents and hematologists was 0.49 (95% CI: 0.29–0.65, P < 0.01), demonstrating a fair inter-observer agreement.

The HEP score does not display a better performance for predicting HIT than the 4T score. With the unsatisfactory completion rate, the inter-observer agreement of 4T score in a tertiary hospital is fair, underscoring the necessity for continuing education for physicians.

There is no absolute consensus for the best time for triggering. The aim of this study was to investigate the effect of different proportion of dominant follicles (PDF) on the human chorionic gonadotropin (HCG) day for the clinical outcomes in patients with polycystic ovary syndrome (PCOS) of different ovarian stimulation protocols.

A total of 371 cycles of the gonadotropin-releasing hormone (GnRH) agonist long protocol and 347 cycles of GnRH antagonist protocol from January 2014 to December 2016 were included in this retrospective study. Based on the PDF on the day of the HCG administration, the included patients were divided into three groups: Group A (low PDF), PDF <20%; Group B (medium PDF), 20%≤ PDF ≤40%; Group C (high PDF), PDF >40%. The measurements regarding ovarian stimulation characteristics, fertilization rate, top quality embryo rate, clinical pregnancy rate, and ovarian hyperstimualtion syndrome (OHSS) rate were compared in different PDF groups with different protocols.

In both the GnRH antagonist protocol and GnRH agonist long protocol, the characteristics such as mean age, anti-Mullerian hormone, antral follicle count (AFC), and body mass index were comparable between groups. The number of oocytes retrieved decreased statistically significantly as the PDF and rate of matured oocytes increased. In the GnRH agonist long protocol, the rate of normally fertilized oocytes was highest in Group A (59.74 ± 31.21 vs. 49.70 ± 37.95, 49.67 ± 36.62; F = 3.743, P = 0.025). There were no significant differences in the rate of top-quality embryos and the clinical pregnancy rate between the groups. The clinical pregnancy rate was similar in the three groups (63.6%, 62.5%, 67.5%, respectively, χ² = 0.989, P = 0.911). The moderate and severe OHSS rate increased statistically significantly when the PDF increased, which was highest in group C (1.4%, 3.1%, 6.7%, respectively, χ² = 12.014, P = 0.017). In the GnRH antagonist protocol, there were no significant differences in the rate of top-quality embryos, the rate of normally fertilized oocytes, the clinical pregnancy rate, and the moderate and severe OHSS rate between the groups. The clinical pregnancy rate in Group C was higher than that in Group A (57.9% vs. 46.6%, χ² = 10.850, P = 0.093).

In the GnRH antagonist protocol, PDF on the HCG day of less than 20% may be unfavorable to the clinical pregnancy rate in PCOS. In the GnRH agonist long protocol, delaying the HCG trigger timing has no good effect on clinical pregnancy and the risk of OHSS might increase in patients with PCOS.

This study was designed to evaluate the clinical and radiographic outcomes of patients with nutcracker syndrome (NCS) who were treated with three-dimensional printing (3DP) extravascular titanium stents (EVTSs). The 3DP EVTS was expected to release the hypertension of the left renal vein (LRV) produced by its compression between the superior mesenteric artery (SMA) and the aorta without causing any complications.

The pre-operative kidney model of each patient was printed out to enable surgical planning. After that, the EVTS was designed based on the LRV’s primitive physiologic structure using computer-aided design software, and each stent was printed out with a precision setting of 20 μm. Seventeen patients who had been suffering from NCS underwent laparoscopic 3DP EVTS placement. The surgical procedure was designed for the placement of EVTS, taking great care in positioning and fixing the stent. Surgical data, which included patient demographic characteristics as well as pre- and post-operative test results, were collected and analyzed.

The mean duration of surgery was 75 ± 9 min, and the mean blood loss was 20 ± 5 mL. Computed tomography examinations revealed that the pre- and post-operative angle between the SMA and the aorta ranged from 18.7° ± 4.3° to 48.0° ± 8.8° (P < 0.05); in patients with left varicocele, the mean diameter of the left spermatic vein ranged from 3.7 ± 0.5 to 1.3 ± 0.2 mm (P < 0.05). Moreover, Doppler ultrasound examinations showed that the peak velocity of blood flow at the hilar area ranged from 12.4 ± 3.3 to 18.5 ± 3.4 cm/s (P < 0.05). No side effects were observed in the 24 to 42 months following surgery.

The findings after 2 years of follow-up suggest that the 3DP EVTS is a safe and effective minimally invasive alternative for the treatment of NCS.

Low handgrip strength (HS) and declining gait speed (GS) are increasingly obvious with aging, requiring effective, and safe medication for treatment. Trimetazidine (TMZ) modified release tablets, a common anti-angina drug, has potential benefits for alleviating the condition, but this has not yet been fully studied and therefore is the aim of this study.

This is a prospective randomized controlled study. Fifty-eight eligible patients will be randomly assigned to one of two study groups: TMZ group or control group. For the TMZ group, a dose of 35 mg of oral TMZ will be administered with a meal twice a day for 3 months, in addition to any conventional treatments for angina. Only conventional treatments for angina will be administrated in the control group. The primary outcome will be the 6-min walking distance and the secondary outcomes will be: muscle strength (HS and pinch strength), GS, muscle endurance (five times sit-to-stand test), balance maintenance (tandem standing test), and the frequency of angina per week. Additionally, body mass index, circumferences (biceps, waist, hip, and calf), albumin levels, and the score on a five-question scale for sarcopenia will be obtained during the study.

This study aims to evaluate the usefulness of TMZ in a population with poor muscle function. The results may provide an effective and safe medical treatment to people with low muscle strength or physical performance.

Chinese Clinical Trial Registry, ChiCTR1800015000; www.chictr.org.cn/showproj.aspx?proj=25445.

The 3-N-butylphthalide (NBP) comprises one of the chemical constituents of celery oil. It has a series of pharmacologic mechanisms including reconstructing microcirculation, protecting mitochondrial function, inhibiting oxidative stress, inhibiting neuronal apoptosis, etc. Based on the complex multi-targets of pharmacologic mechanisms of NBP, the clinical application of NBP is increasing and more clinical researches and animal experiments are also focused on NBP. The aim of this review was to comprehensively and systematically summarize the application of NBP on neurologic diseases and briefly summarize its application to non-neurologic diseases. Moreover, recent progress in experimental models of NBP on animals was summarized.

Literature was collected from PubMed and Wangfang database until November 2018, using the search terms including "3-N-butylphthalide," "microcirculation," "mitochondria," "ischemic stroke," "Alzheimer disease," "vascular dementia," "Parkinson disease," "brain edema," "CO poisoning," "traumatic central nervous system injury," "autoimmune disease," "amyotrophic lateral sclerosis," "seizures," "diabetes," "diabetic cataract," and "atherosclerosis."

Literature was mainly derived from English articles or articles that could be obtained with English abstracts and partly derived from Chinese articles. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors’ files.

NBP has become an important adjunct for ischemic stroke. In vascular dementia, the clinical application of NBP to treat severe cognitive dysfunction syndrome caused by the hypoperfusion of brain tissue during cerebrovascular disease is also increasing. Evidence also suggests that NBP has a therapeutic effect for neurodegenerative diseases. Many animal experiments have found that it can also improve symptoms in other neurologic diseases such as epilepsy, cerebral edema, and decreased cognitive function caused by severe acute carbon monoxide poisoning. Moreover, NBP has therapeutic effects for diabetes, diabetes-induced cataracts, and non-neurologic diseases such as atherosclerosis. Mechanistically, NBP mainly improves microcirculation and protects mitochondria. Its broad pharmacologic effects also include inhibiting oxidative stress, nerve cell apoptosis, inflammatory responses, and anti-platelet and anti-thrombotic effects.

The varied pharmacologic mechanisms of NBP involve many complex molecular mechanisms; however, there many unknown pharmacologic effects await further study.

To the Editor:Compared with trans-femoral artery access (TFA), trans-radial artery access (TRA) for percutaneous coronary interventions (PCI) has been shown to significantly reduce 30-day mortality, in-hospital major adverse cardiac and cardiovascular events (a composite of 30-day mortality and in-hospital myocardial re-infarction, target vessel revascularization, and cerebrovascular events), major bleeding, and access site complications.^[1]TRA is more easily compressible, minimizing hematoma risk, and lower crossover rates to another access. Patients may ambulate immediately after procedure, that hospitalization can be shortened significantly. In some centers, patient with TRA can be discharged on the same day of procedure. It is also superior to TFA with closure devices, and becomes the preferred access site for recent PCI.^[2]

To the Editor:Persistent fifth aortic arch (PFAA) is a rare congenital cardiovascular malformation that occurs when the pharyngeal fifth aortic arch does not degenerate during the embryonic period. The first case of PFAA was described in an autopsy specimen in 1969.^[1]In 1973, the persistence of a left fifth aortic arch was first reported.^[2]Since then, several case reports have described PFAA in different forms. PFAA stenosis associated with type A interruption of the aortic arch (type-A IAA) is most common in clinical practice and requires surgical intervention. From 2013 to 2018, six cases [Table 1andTable 2] were diagnosed using echocardiography and computed tomography angiography (CTA). Five cases were successfully treated with surgery and followed-up. The purpose of this study was to summarize the clinical characteristics and diagnostic features of PFAA stenosis associated with type-A IAA to improve its diagnostic accuracy and allow for complete pre-operative preparation and proper treatment.

To the Editor:An 89-year-old woman was admitted with a 3-day history of dysphagia and lower jaw twitching. She had a history of hypertension, diabetes mellitus, surgically corrected left proximal humeral fracture, and right C5 dermatome postherpetic neuralgia. The jaw twitching had caused dysphagia with an inability to drink liquids. Physical examination confirmed the persistent lower jaw myoclonus (Supplementary Video; http://links.lww.com/CM9/A48). The patient was fully conscious and had no twitching or nystagmus in any of her other extremities. The results of neurological examination and biochemical analysis (including complete blood profile, electrolyte level, random glucose concentration, renal function test, and liver function test) were all within the normal range. Computed tomography of the brain was unremarkable and an electroencephalogram showed no evidence of seizure. A careful review of her prescribed medications revealed the following: the patient complained of allodynia over the right C5 dermatome around 3 months prior and was prescribed gabapentin. The dosage of gabapentin was increased to 300 mg total dissolved solids (TDS) around 2 months prior. Creatinine levels were normal but her glomerular filtration rate, as estimated by the Cockcroft-Gault equation, was 36 mL/min.^[1]Since the patient’s relatives supervised her medication intake, overdosage was not possible. Gabapentin was discontinued and replaced with pregabalin 50 mg BD and the patient was prescribed valium 2 mg TDS transiently. The jaw myoclonus subsided on the second day. After a consultation with a speech therapist, the patient resumed oral intake and remained tolerant of a normal diet. Upon review after 1 month, the patient remained free from jaw myoclonus.

To the Editor:Amyotrophic lateral sclerosis (ALS) is a heterogeneous disorder characterized by a loss of upper and lower motor neurons with neither clear pathogenesis nor effective treatment. Thus, potential biomarkers are needed to classify the disease and find new drug targets. Previous studies have shown that auto-antibodies against the low-density lipoprotein receptor-related protein 4 (LRP4), called the anti-LRP4 antibodies, are found in ~23% patients of Greek and Italian ALS cohorts,^[1]and in 10% of the American ALS population.^[2]Anti-LRP4 antibodies were previously identified in myasthenia gravis (MG), the most common neuromuscular junction (NMJ) disorder, and were shown to cause NMJ abnormality in animal studies.^[3]Here, we studied anti-LRP4 antibodies in Chinese patients and investigated the correlation between anti-LRP4 antibodies and abnormal neuromuscular transmission in ALS.

To the Editor:Alzheimer disease (AD) is the most common neurodegenerative disorder, accounting for the majority of cases of dementia. The global prevalence of AD is rising, representing an increasing challenge for older individuals and their families.^[1]Seven out of every ten patients with AD receive informal care at home, relying on co-resident family members, especially spouses.^[2]However, cultural differences exist in the effects of the disorder. For example, Chinese caregivers of patients with dementia had higher scores on measures of depression and caregiver burden compared with caregivers of patients with dementia in Western societies.^[3]It is important to consider that AD not only affects the patient but also their caregivers, particularly spousal caregivers who spend more than half their time with the patient.^[4]As AD progresses, patients become increasingly dependent on caregivers. Meanwhile, there is an increasingly heavy caregiver burden, characterized as the physical, psychological, or emotional, social, and financial problems experienced by family members who care for impaired older adults.^[5]Additionally, it is frequently reported that sleep disturbance symptoms are associated with health consequences among AD caregivers.^[6]

To the Editor: Mycoplasma pneumoniaeis a common pathogen that leads to respiratory tract infections in children, often causing immune-related injuries in multiple other organs and tissues. The involvement of central nervous system has been reported in 5% to 7% of patients withM. pneumoniaeinfection.^[1]The clinical manifestations ofM. pneumoniaeencephalitis are highly heterogeneous, and more than half of patients experience seizures during the acute phase, with status epilepticus occurring in severe cases.^[2]

To the Editor: A 24-year-old female patient was admitted to our department with complaints of fatigue and pedal edema. She was diagnosed with systemic lupus erythematosus (SLE) 4 years ago and thus the diagnostic criteria could not be traced. She had been treated with prednisolone, hydroxychloroquine, and cyclophosphamide for 2 years, and her disease was controlled in stable condition. Occasionally, pain on her lower extremity was her only complaint, which could be relieved by prednisolone. Eight months before admission to our hospital, she got progressive abdominal distension and edema of lower extremities. Abdominal ultrasonography at the local hospital showed ascites; so the patient was treated with diuretic, which made her feel much better. But the patient presented herself with shortness of breath to the local hospital 5 months later. Computed tomography (CT) scan of the thorax showed bilateral pleural effusion. Again, she took diuretic but no significant relief was achieved. In March 2017, the patient was admitted to our department. On physical examination, she had a normal temperature and blood pressure. She was identified with diminished breath sounds, ascites, and edema of the two legs. Her ankles were swollen and tender. Laboratory findings were as follows: white blood cell (WBC) was 1340/mm³, but there was no anemia or thrombocytopenia. C-reactive protein was 14 mg/dL. The antinuclear antibody titer was 1:320 (granular type), whereas anti-double-stranded DNA antibody, anti-Sm antibody, anticardiolipin antibodies, and lupus anticoagulant were negative. Complement C3 was 45.1 mg/dL (normal range 78.5–152.0 mg/dL) and C4 was 4.84 mg/dL (normal range 14.5–36 mg/dL). Coombs test was positive. Proteinuria was quantified at 0.36 g/24 h and kidney function was normal. Albumin was 3.35 g/dL and ferritin was 42.49 ng/mL. CA125 was 949 IU/mL (normal range 0–35 IU/mL), whereas other tumor markers including alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), and CA199 were normal. CT scan of the thorax showed pleuropericardial effusions, and abdominal ultrasonography showed massive ascites and splenomegaly.

To the Editor:Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic vascular disorder characterized by multiple venous malformations involving many organs. BRBNS can occur in various organs, but the most frequently involved organs are the skin and gastrointestinal tract. Gastrointestinal lesions of BRBNS can cause acute or chronic bleeding and anemia.^[1]Only several case reports of pregnant women with BRBNS could be found in the current database and most of them were complicated by hemorrhage of the gastrointestinal tract. We report a case of BRBNS during pregnancy that suffered from severe pulmonary embolism (PE) and was successfully resuscitated.

To the Editor:A 46-year old woman (gravida 3, para 1) presented at West China Second Hospital with complaints of a space-occupying lesion in the uterus that, 2 years before, had been diagnosed as a uterine cyst at West China Second Hospital. On that previous occasion, B-ultrasonography revealed a cystic mass with a compartmentalized structure (10.3 × 5.4 × 8.8 cm) on the left side of the pelvic cavity, and laparoscopic exploration found a cystic mass on the posterior uterine wall, which was diagnosed as "leiomyoma with cystic degeneration" based on pathology analysis of flash-frozen surgical tissues. Laparoscopic "myomectomy" was performed, and pathology analysis of paraffin-embedded tissue confirmed "leiomyoma with degeneration." Immunohistochemistry showed the lesion to be positive for caldesmon but negative for CD10. Rate of Ki67 positivity was less than 1%, indicating a benign lesion. The woman recovered well after the operation. Follow-up ultrasonography at 3 months after surgery identified a uterine cystic mass of 3.0 × 2.5 × 1.7 cm.

To the Editor:Pancreatic cancer (PC), a deadly malignancy with an overall 5-year survival rate of 5% to 15%, is ranked as the seventh leading cause of cancer death in the world in spite of its low occurrence rate.^[1,2]Early detection appears to be the most effective approach to improve the overall survival of patients with PC. However, the difficulty in early detection of PC is a lack of specific symptoms and reliable biomarkers. Currently, carbohydrate antigen 19-9 (CA 19-9) is a serum biomarker that is widely used in PC detection. However, 10% of patients with PC cannot produce CA 19-9 and serum CA 19-9 is frequently absent in patients with early-stage cancer. Furthermore, CA 19-9 is often found to be elevated in benign conditions or in other cancers, making its utility limited. Therefore, it is important to identify new diagnostic biomarkers to improve PC detection.

We appreciated reading the article by Zhanget al^[1]about a retrospective study of 102 mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients with epilepsy in which disability and outcome were assessed (median follow-up: 4 years). Administration of levetirazetam (LEV) was associated with a better outcome compared to other antiepileptic drugs (AEDs).^[1]The study has several shortcomings requiring discussion.