bluuebunny/crossref_metadata_2025 huggingface dataset:
667. Preclinical Pharmacokinetic and Pharmacodynamic Characterization of EDP-938, a Novel and Potent NonFusion Replication Inhibitor of Respiratory Syncytial Virus
Authors: Jiang Li-Juan , Xu Lisha , Huang Meng , Zhang Shucha , Li Yang , Zang Indy , Kibel Jonathan , Adams Madison , Labrecque Noelle , Rhodin Michael , McAllister Nicole , Lin Kai , Jong Kim In , Sun Or Yat
Published: July 2020

Background

Respiratory syncytial virus (RSV) infection presents a significant health challenge in young children, elderly and immunocompromised patients. To date, there are no effective treatments available. EDP-938 was designed to meet this unmet medical need and is currently in Phase 2 clinical trials. Herein we report its preclinical pharmacokinetic (PK) and pharmacodynamic (PD) properties.

Methods

The pharmacokinetics of EDP-938 following single intravenous and oral doses were determined in mice, rats, dogs, and monkeys. In vitro cellular permeability and metabolic stability were assayed using Caco-2 cells and human liver microsomes, respectively. In vivo pharmacodynamic efficacy of EDP-938 was conducted in the African green monkey model, in which animals experimentally challenged with RSV were orally dosed twice daily with 100 mg/kg EDP-938 for 6 days starting 24 hours prior to infection.

Results

EDP-938 was well absorbed in the preclinical species with oral bioavailability values ranging from 27.1% in dogs, 35.4% in mice, 35.7% in rats, and 39.5% in monkeys, after a single oral dose when formulated in 0.5% methylcellulose. EDP-938 showed a moderate in vitro permeability of 3.6 x 10–6 cm/sec in Caco-2 cells. Based on the outcome of these absorption studies, EDP-938 was projected to have good oral absorption in humans. EDP-938 had low intrinsic clearance of 5 mL/minute/mg in human liver microsomes. Moreover, EDP-938 demonstrated potent antiviral efficacy in an African green monkey model of RSV infection. In untreated monkeys the RSV RNA viral load in the bronchoalveolar lavage fluid peaked at 106 copies/mL on day 5 post-infection, by comparison in animals treated with EDP-938 the viral load was below the limit of detection by day 3 post-infection. The PK/PD modeling suggested that plasma trough concentrations ≥10 × EC90 led to >4-log viral load reduction in EDP-938 treated monkeys.

Conclusion

The favorable preclinical PK and PD properties of EDP-938 support its further clinical development as a novel treatment for RSV infection.

Disclosures

All authors: No reported disclosures.
0264 Childhood Adversity And Adult Sleep: The Role Of Deprivation And Threat
Authors: Cribbet Matthew R , Williams Paula G , Tinajero Ruben , Rau Holly K
Published: July 2020

Introduction

There are robust associations between childhood adversity (CA) and poor physical health in adulthood. Sleep is a possible mechanism linking CA to adult health. The prevailing approach for testing associations between CA and adult sleep offers little insight into which aspects of CA are related to specific sleep outcomes. To better understand associations between CA and adult sleep outcomes, we tested a conceptual model that distinguishes between threat (e.g. physical, emotional and sexual abuse), and deprivation (e.g. emotional and physical neglect).

Methods

Participants (N= 79; Mage = 27.48(SD=6.53); 68% Female) were screened for insomnia disorder, mental health conditions and physical illnesses. Participants completed demographic and depressive symptom measures, along with the Childhood Trauma Questionnaire, a self-report retrospective measure that captures dimensions of threat and deprivation. Sleep duration, latency, efficiency, wake after sleep onset (WASO), and secondary sleep onset latency (SSOL) were averaged across 3 consecutive days of wrist actigraphy and sleep diaries. Daily ratings of sleep-quality, non-restorative sleep, alcohol use and current stress were averaged across 3 days. Structural equation modeling (SEM) was used to account for missing data. All SEM models included correlated measures of deprivation and threat along with age, sex, BMI, alcohol use, daily stress, and depressive symptoms.

Results

In SEM models, threat was significantly positively associated with non-restorative sleep (b = .046, p <.001) and sleep quality (b=.025, p=.008), but unrelated to all other diary-based and actigraphy-based sleep measures (ps > .05). Deprivation was significantly negatively associated with diary-based WASO (b = -.076, p = .003) and SSOL, but unrelated to all other diary-based and actigraphy-based sleep measures (ps > .05).

Conclusion

These results begin to clarify associations between related, but distinct forms of CA and specific adult sleep outcomes. Identifying specific pathways linking CA and adult health is critical for developing interventions and mitigating future health risk.

Support (If Any)

This study was funded by a Funding Incentive Seed Grant from the University of Utah, the Mind and Life Institute, and Division 38 of the American Psychological Association.
Cowan v Scargill and the fiduciary duty of investment: has the nature of the investment duty changed and what is currently driving “socially responsible investing” in pension schemes?
Authors: Brown Lloyd
Published: July 2020

This article examines the fiduciary duty of investment. It is particularly interested in how this duty may be exercised by pension trusts in support of the “socially responsible investing” (SRI) movement. An analysis of the case of Cowan v Scargill is provided to better understand whether this duty has changed over the past two decades. It finds that the above-named case shows that, intrinsically, this duty has not changed. In light of that finding, the article stipulates that external stimuli, in the form of increased regulation and societal appreciation of SRI, are driving improvements in this area.
Familial cerebral cavernous malformation presenting with epilepsy caused by mutation in the CCM2 gene
Authors: Ishii Kazuhiro , Tozaka Naoki , Tsutsumi Satoshi , Muroi Ai , Tamaoka Akira
Published: July 2020

Rationale:

Cerebral cavernous malformation (CCM) of the familial type is caused by abnormalities in the CCM1, CCM2, and CCM3 genes. These 3 proteins forming a complex associate with the maintenance of vascular endothelial cell-cell junctions. Dysfunction of these proteins results in the development of hemangiomas and abnormal intercellular junctions.

Patient concerns:

We report a 68-year-old man with familial cerebral cavernous malformation with initial presentation as convulsions at an advanced age. Brain magnetic resonance imaging revealed multiple cavernous hemangiomas in the right occipital lobe. The convulsions were considered to be induced by hemorrhage from cavernous hemangioma in the right occipital lobe.

Diagnoses:

Genetic screening of the CCM1, CCM2, and CCM3 genes revealed a novel mutation in the CCM2 gene (exon4 c: 359 T>A, p: V120D). No abnormalities were found in CCM1 or CCM3. Therefore, we diagnosed the patient with familial CCM caused by a CCM2 mutation.

Interventions:

This patient was treated with the administration of levetiracetam at a dosage of 1000 mg/day.

Outcomes:

No seizures have been observed since the antiepileptic drug was administered. We performed brain magnetic resonance imaging (MRI) regularly to follow-up on appearance of new cerebral hemorrhages and cavernous hemangiomas.

Lessons:

This report reviews cases of familial cerebral cavernous malformations caused by abnormalities in the CCM2 gene. This mutation site mediates interactions with CCM1 and CCM3. The mutation occurs in the phosphotyrosine binding (PTB) site, which is considered functionally important to CCM2.
Efficacy of transconjunctival approach for the treatment of orbital fractures
Authors: Qi Yan-Xiu , Li Si-ying , Wang Dong-lan , Zhou Ping-ping
Published: July 2020

Background:

This study aims to assess the efficacy of transconjunctival approach (TCA) for the treatment of orbital fractures (OF) comprehensively and systematically.

Methods:

In this study, we plan to search electronic databases of Cochrane Library, MEDLINE, EMBASE, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure and for relevant randomized controlled trials. All these databases will be searched from inception to the March 1, 2020 without limitations of language and publication status. Two independent authors will carry out study selection, data collection, and study quality assessment. Any disagreements will be resolved by discussion with another author if necessary. The study quality will be assessed using Cochrane risk of bias tool. Statistical analysis will be conducted using RevMan 5.3 software.

Results:

This study will be the first 1 to exert direct evidence to evaluate the efficacy of TCA for the treatment of OF.

Conclusions:

The findings of this study will provide an exhaustive view of TCA for the treatment of OF.

Study registration number:

INPLASY202040154.
Clinical efficacy of Duyiwei capsule in treating gingivitis
Authors: Liu Hai-Ying , Fan Jing-Hui , Lin Na , Zhao Zhi-Xuan
Published: July 2020

Background:

This study will investigate the clinical efficacy of Duyiwei capsule (DYWC) for the treatment of gingivitis.

Methods:

Relevant studies will be searched in PUBMED, EMBASE, Cochrane Library, WANGFANG, VIP, CBM, and CNKI from inception to the March 31, 2020 without limitations of language and publication time. All potential randomized controlled trials on the clinical efficacy of DYWC for the treatment of gingivitis will be considered. Two authors will independently perform literature selection, data collection, and study quality assessment. Any disagreements will be solved by a third author through discussion. We will utilize RevMan 5.3 software for statistical analysis.

Results:

This study will summarize present randomized controlled trials on the efficacy and safety of DYWC for the treatment of gingivitis.

Conclusion:

The findings of this study will provide evidence to show whether DYWC is effective and safety for gingivitis.

Systematic review registration: INPLASY202040199.
Acupotomy therapy for cervical vertigo
Authors: Xie Rongfang , You Jianyu , Liu Liting , Huang Chunhua , Liang Yu
Published: July 2020

Background:

Acupotomy has been widely used to relieve cervical vertigo (CV). However, the efficacy of acupotomy for CV is uncertain. The purpose of this study is to evaluate the efficacy and safety of the acupotomy for CV.

Methods:

The following electronic databases will be searched to identify relevant randomized controlled trials (RCTs) for inclusion in the review from inception to April 2020: PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database. Two researchers will independently select studies, collect data, and assess the methodology quality by the Cochrane risk of bias tool. Meta-analysis will be completed by RevMan V.5.3 software.

Results:

This systematic review will provide an assessment of the current state of acupotomy for CV, aiming to assess the efficacy and safety of acupotomy for Patients with CV.

Conclusion:

This systematic review will provide a credible Evidence-based for the clinical treatment of CV with acupotomy.

PROSPERO registration number: CRD42019134712.
Healthcare access for autistic adults
Authors: Calleja Shenae , Islam Fakir M. Amirul , Kingsley Jonathan , McDonald Rachael
Published: July 2020

Background:

People with autism spectrum disorder (ASD) have an increased susceptibility for many chronic health conditions compared with their peers. An increasing number of adolescents are transitioning from pediatric to adult healthcare services. Thus, being able to access appropriate healthcare services that can not only address specific needs of the person but enable them to better manage healthcare conditions and decrease the development of preventable disease is necessary. A systematic review was conducted to identify barriers and enablers of healthcare access for autistic adults.

Methods:

The studies included in the review were quantitative and qualitative and were published between 2003 and 2019. The participants for the review are considered to be adults (over 18 years of age) with a primary diagnosis of ASD.

Results:

In total, 1290 studies were initially identified and 13 studies were included based on the inclusion and exclusion criteria outlined in a previous protocol paper. The analysis of these studies identified areas of concern to access appropriate healthcare, such as clinician knowledge, the environment, and life events.

Conclusion:

Identifying the barriers to healthcare, highlights ways healthcare services can regulate scope of practice, the physical environment, and the process of managing health conditions, thus, autistic adults can strive for optimal health. This review contributes to peer-reviewed evidence for future research and up-to-date information when developing and piloting health interventions for autistic adults.

Ethics and dissemination:

There are no human participants, data, or tissue being directly studied for the purposes of the review; therefore, ethics approval and consent to participate is not applicable.

Registration and Status:

PROSPERO 2018 CRD42018116093
Presence of red flags in patients with cerebral venous sinus thrombosis admitted to the emergency department because of headache
Authors: García-Azorín David , Monje Mariana H.G. , González-García Nuria , Guerrero Ángel L. , Porta-Etessam Jesús
Published: July 2020

Cerebral venous sinus thrombosis (CVST) is a cause of secondary headache with substantial morbimortality. Headache dominates the clinical presentation, but no typical phenotype has been described. We aim to evaluate the presence of red flags in headache in patients with confirmed CVST at the moment of emergency department (ED) presentation.

Retrospective STROBE compliant cohort study including patients with confirmed CVST that consulted because of headache at the ED. We analyzed presence and type of red flags at the moment of consult. We evaluated whether CVST was suspected at the moment of imaging request and analyzed delay in the diagnosis.

Nineteen patients fulfilled inclusion and exclusion criteria. Mean age was 48.5 years, 47.4% were female. All the studied patients exhibited at least 1 red flag, being abnormal neurological examination the most frequent (79%), followed by the presence of other neurological symptoms (68%), alarm data related with headache phenotype (63%), or risk factors concerning prior medical history (47%). Temporal pattern of the headache was acute in 42.1%, thunderclap in 31.6%, and subacute in 26.3%. In none patient CVST was the specific suspicion when imaging was requested. Median time since headache onset and ED presentation was 84 hours, being different in patients with associated symptoms (48 hours) when compared with isolated headache patients (168 hours). Time since ED presentation and the diagnosis also differed between the 2 groups, being more prolonged in patients with an isolated headache at presentation.

Headache attributed with CVST did not exhibit any distinctive phenotype, but all the patients presented some red flag, being abnormal neurological examination the most frequent.
Schwannoma in the hepatoduodenal ligament with portal vein invasion
Authors: Wang Jun-Ke , Wu Qian , Wu Zhen-Ru , Liu Fei , Ran Cong-Dun , Yin Chang-Hao , Li Fu-Yu
Published: July 2020

Rationale:

Schwannomas are mesenchymal tumors with low malignant potential that originate from Schwann cells. They can occur in most parts of the body, such as the head, neck, and extremities. Schwannoma in the hepatoduodenal ligament is extremely rare, and only four cases have been reported in the literature.

Patient concerns:

Herein, we describe a 58-year-old female who presented with right epigastric pain for 10 days. Preoperative computed tomographic (CT) revealed a 4.5 cm × 3.8 cm tumor in the hepatic hilar area.

Diagnoses:

Schwannoma in the hepatoduodenal ligament with portal vein invasion.

Interventions:

Intraoperative findings revealed that the tumor was identified in the hepatoduodenal ligament, and the left branch of the portal vein was compressed. Complete tumor resection with reparation of the portal vein was performed for the patient. Postoperative pathological examination confirmed the final diagnosis of benign schwannoma, characterized by abundant spindle-shaped cells and positive reactivity for S-100 protein.

Outcomes:

The patient had a good prognosis and had no recurrence after 37 months of follow-up.

Lessons:

Our case of schwannoma in the hepatoduodenal ligament is unique owing to the portal vein invasion, aimed at helping recognize the difficulty of preoperative diagnosis.
Risk factors for venous thromboembolism following spinal surgery
Authors: Zhang Lu , Cao Hongxin , Chen Yunzhen , Jiao Guangjun
Published: July 2020

Background:

To investigate the risk factors for postoperative venous thromboembolism (VTE) in patients undergoing spinal surgery.

Methods:

Literature published in PubMed, Embase, the Cochrane Library, and Web of Science was systematically reviewed to assess risk factors for VTE following spinal surgery. The data analysis was conducted with STATA 12.0. Data were pooled using fixed-effects or random-effects models according to the heterogeneity among the included studies.

Results:

Twenty-six studies involving 3,216,187 patients were included in this meta-analysis, and the total incidence of VTE after spinal surgery was 0.35% (0.15–29.38%). The pooled analysis suggested that the incidence of VTE after spinal surgery was higher in such aspects as increasing age (weighted mean difference [WMD] 0.55 years, 95% confidence interval [CI] 0.33–0.78, P < .001), female sex (odds ratio [OR] 1.12, 95% CI 1.01–1.25; P = .034), diabetes (OR 1.34, 95% CI 1.29–1.44; P < .001), chronic kidney disease (OR = 8.31, 95% CI 1.98–34.93; P = .004), nonambulatory preoperative activity status (OR 3.67, 95% CI 2.75–4.83; P < .001), D-dimer level (WMD 1.023, 95% CI 0.162–1.884; P = .02), long duration of operation (WMD 0.73, 95% CI 0.21–1.24; P = .006), spine fusion (OR 1.54, 95% CI 1.31–1.82; P < .001), and blood transfusion (OR 2.31, 95% CI 1.73–3.07; P < .001), and the differences were statistically significant. However, there were no significant differences in body mass index, obesity, hypertension, coronary heart disease, spondylolisthesis, intraoperative blood loss, surgical procedures (anterior lumbar interbody fusion vs posterior intervertebral fusion /translaminar lumbar interbody fusion), or surgical site (lumbar vs thoracic) (all P > .05).

Conclusion:

Based on our meta-analysis, we identified several important factors that increased the risk of VTE after spinal surgery. We hope our study provides assistance to spine surgeons so that they can adequately analyze and assess risk factors in patients and then develop preventive measures to reduce the incidence of VTE.
Comparison of arthroscopic single-row and double-row repair in the treatment of rotator cuff tears
Authors: Lin Yanming , Zhao Jiasong , Qiu Heng , Huang Yong
Published: July 2020

Background:

Single-row (SR) and double-row (DR) techniques are 2 kinds of widely used approaches for the arthroscopic repair of rotator cuff. This retrospective clinical trial was performed to address the question of whether a DR rotator cuff anchor repair gives results superior to a SR anchor repair in clinical outcome scores and complication rates.

Methods:

This study was performed and reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology checklist. We retrospectively reviewed our database, which was collected prospectively. From 2014 to 2017, 264 patients underwent arthroscopic rotator cuff repair by an experienced single shoulder surgeon with the SR and DR techniques. This study was approved by the institutional review board in our hospital and was registered in the Research Registry. Outcome measures included Constant-Murley score, muscle strength, patient satisfaction, passive range of motion, and retear rates.

Results:

The hypothesis was that the DR technique would achieve better functional scores and fewer complications as compared to the SR technique in treatment of rotator cuff tears.
Hearing impairment in young and middle-aged septicemia survivors
Authors: Cheng Chun-Gu , Chien Wu-Chien , Lin Hung-Che , Lin Hui-Chen , Chung Chi-Hsiang , Cheng Chun-An
Published: July 2020

The ability of sepsis to induce acute phase hearing impairment has been evaluated in septic and sepsis-surviving mice. The relationship between septicemia and long-term hearing impairment remains unknown in humans.

The data were obtained from the Taiwan Longitudinal National Health Insurance Database from 2000 to 2013. We identified patients suffering from septicemia after discharge, excluding those younger than 18 years old and older than 65 years old. The comparison group was matched based on age, sex, and comorbidities. The outcome was hearing impairment occurring after septicemia. The risk factors associated with hearing impairment were established using multivariate Cox proportional hazard regression.

Our study found that septicemia associated with hearing impairment had an adjusted hazard ratio (HR) of 53.11 (95% confidence interval [CI]: 41.74–67.59). The other factors related to hearing impairment in young and middle-aged septicemia survivors included male sex (adjusted HR 1.31 [95% CI: 1.14–1.5]), chronic kidney disease (adjusted HR 1.63 [95% CI: 1.38–1.94]), and otoscleroisis (adjusted HR 231.54 [95% CI: 31.61–1695.8]).

Our study revealed that septicemia was associated with increased development of hearing impairment in young and middle-aged humans in the long term. Clinicians should be aware of long-term septicemia-related hearing impairment and provide prevention strategies for otopathy in septicemia survivors.
Effects of Fusu mixture (Wen-Shen-Qian-Yang Method) on sepsis-induced acute respiratory distress syndrome
Authors: Zhang Li , Long Kunlan , Wang Chunxia , Zhang Xuemei , Yang Hongjing , Chen Jun , Li Xue , Gao Peiyang , Zhang Song
Published: July 2020

Introduction:

Sepsis is the most common etiology of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Capillary leakage caused by lung endothelial injury is the central cause of ARDS. The results of research in modern medicine in reducing endothelial damage and restoring endothelial functions are limited. In the previous clinical observations, we found that the Fusu mixture not only improves the clinical symptoms but also reduces the leakage of pulmonary capillaries. Therefore, the purpose of this study is to determine the clinical efficacy of the Fusu mixture combined with Western medicine in the treatment of ARDS caused by sepsis and to explore the mechanism of traditional Chinese medicine.

Methods:

This is a prospective, single-center, randomized, single-blind, and controlled clinical study involving 620 eligible patients. The patients will be randomly divided into 2 groups: the Western medicine treatment group and the combination of Chinese and Western medicine treatment group. After 14 days of intervention, the clinical efficacy and safety of the Fusu mixture on sepsis-induced ARDS patients will be observed. The primary outcome will be measured as 28-day mortality. The secondary outcome indices include inflammatory markers (CRP, PCT, IL-6, TNF - α), APACHE II score, SOFA score, days without a ventilator, blood gas analysis (Lac, PaO2 / FiO2), intensive care unit hospital stay time, intensive care unit mortality. Simultaneously, the analysis of the exploratory results will be carried out to analyze the possible mechanism of Fusu mixture in the treatment of sepsis-induced ARDS by the high-throughput sequencing and bioinformatics.

Discussion:

The purpose of this study is to evaluate the clinical efficacy of Fusu mixture in the treatment of sepsis-induced ARDS and explore its possible mechanism of action. If successful, it will provide evidence-based adjuvant therapy for the clinical treatment of ARDS.
Treatment of acute urticaria with acupuncture
Authors: Zhou Shuai , Zhao Ruirui , Xue Mingxin
Published: July 2020

Rationale:

Urticaria is a refractory dermatosis with long duration and a high recurrence rate. More to the point, medication of acute urticaria always demands high doses, which may cause some adverse effects. Acupuncture, with a history for over 2000 years, has been utilized in clinical practice as an alternative treatment strategy for dermatologic diseases.

Patient concerns:

A 26-year-old male nurse on duty suddenly fell sick during the night-shift in the ward. Wheals began spreading all over his body, but he had no urticaria medicine on hand. The unbearable itching made it extremely difficult for him to resume working.

Diagnosis:

The patient was diagnosed with acute urticaria according to the symptoms.

Interventions:

A 30-minute acupuncture treatment was performed.

Outcomes:

About 5 minutes after needles were inserted into the acupoints, the patient felt significantly relieved of itching sensation; moreover, he could even subjectively control himself from scratching and could calmly wait for gradual disappearance of the wheals. Then 30 minutes later, the wheals almost faded away.

Lessons:

The results suggest that acupuncture may be a promising alternative therapy to treat acute urticaria, especially for patients who cannot receive drug treatment.
Fu's subcutaneous needling for subcutaneous adhesions and scar hyperplasia in the neck region
Authors: Huang Huixia , Liu Jin , Fu Mingquan , Lin I-Wen , Chou Li-Wei
Published: July 2020

Rationale:

Lymphadenectomy for tongue cancer in the neck region is often accompanied by local impaired mobility, gland damage, difficult in swallowing, and postoperative complication and seriously affects patients life quality. We reported a case of subcutaneous adhesions and scar hyperplasia in the neck region after lymphadenectomy for tongue lesions accompanied by impaired neck mobility and difficult in swallowing was treated using Fu's subcutaneous needling (FSN) treatment.

Patient concerns:

A 55-year-old male with tongue cancer received surgical intervention with lymphadenectomy 8 years ago was revealed a 15 cm-long curved surgical incision in the neck region and surrounded by numerous scar tissues.

Diagnosis:

Post-operation subcutaneous adhesions and scar hyperplasia in the neck region after lymphadenectomy was diagnosed.

Interventions:

FSN treatment was performed 2 to 3 times per week for 1 month to sway the affected tightened muscle and dissociate the superficial fascia beneath the scar resulted in a considerable improvement in neck movement.

Outcomes:

The Vancouver Scar Scale (VSS) was as follows: color (M) - 1; vascular distribution (V) - 0, thickness (H) - 2, and flexibility (P) - 4, with a total of 7 points before FSN treatment. The VSS after 1 month of FSN treatment was as follows: M1, V0, H2, and P2, with a total of 5 points. Neck mobility in different directions, i.e., stretching to the back of the neck and laterally bending the neck to the left and/or right side, was improved (P < .05).

Lessons:

At present, treatment of chronic scar hyperplasia has certain side effects and limitations. FSN is safe and convenient, with minimal destruction of the superficial fascia, having evident effects of dissociating tissue adhesion under scars and compensating for deficiencies in scar hyperplasia treatment. It can provide new ideas for future treatments.
Acute fatty liver of pregnancy cases in a maternal and child health hospital of China
Authors: Wang Ling , Gan Quan , Du Shuguo , Zhao Yun , Sun Guoqiang , Lin Ying , Li Ruyan
Published: July 2020

Rationale:

Acute fatty liver of pregnancy (AFLP) is extremely hazardous to pregnant woman in the 3rd trimester of pregnancy. AFLP has an insidious onset and nonspecific experimental indicators, which therefore is difficult to be diagnosed.

Patient concerns:

Case 1 was transferred to our hospital for hypertensive disorders complicating pregnancy at gestation of 38 weeks + 3 days. Case 2 was transferred to our hospital for suspicious fetal heart monitoring response at gestation of 36 weeks + 4 days. Case 3 was transferred to our hospital for prelabor rupture of membranes at gestation of 37 weeks + 1 days.

Diagnosis:

The diagnosis of AFLP was based on the Swansea criteria.

Interventions:

All 3 cases were delivered by cesarean section, and they were all transferred to intensive care unit for further treatment. Cases 2 and 3 were subjected to plasma exchange and continuous renal replacement therapy.

Outcomes:

In this study, all 3 patients were initially diagnosed as gastritis. In addition, case 1 was diagnosed as preeclampsia and her AFLP was misdiagnosed with postpartum hemorrhage after cesarean delivery. Case 2 was admitted to the hospital for intrahepatic cholestasis of pregnancy and fetal distress, but we considered it as AFLP before delivery. Case 3 was treated according to severe intrahepatic cholestasis of pregnancy, but we rediagnosed it as postpartum hemorrhage and disseminated intravascular coagulation after cesarean delivery. Neonatal asphyxia and complications were not found. All of the 3 cases were fully recovered and discharged from our hospital.

Lessons:

If there are multiple risk factors including vomiting, abdominal pain, and fetal distress, AFLP should be highly suspected. Early diagnosis, especially before termination of pregnancy, is the key to successful treatment of AFLP.
Primary anaplastic large cell lymphoma of the central nervous system in a child
Authors: Feng Shuo , Chen Qian , Chen Jinxiao , Zheng Ping , Ma Kangping , Tan Bojing
Published: July 2020

Introduction:

To report the clinical characteristics of primary central nervous system T-cell lymphoma with anaplastic lymphoma kinase-1 (ALK-1) positive in an 8-year-old male.

Patient concerns:

The patient presented cognitive impairment, dizziness, vomiting, fever, and convulsions during the disease, followed by progressive and persistent severe headache, progressive increase of intracranial pressure, indifference, disorder of consciousness, mild increase in white blood cells in cerebrospinal fluid, progressive decrease of sugar, progressive increase of protein, abnormal signal of left parietal-occipital, local meningeal enhancement, and cerebrospinal fluid cytology.

Diagnosis:

He was diagnosed with ALK-1-positive central nervous system T-cell lymphoma.

Interventions:

Meropenem and vancomycin were administered to counter the infection, while dexamethasone alleviated the inflammation.

Outcomes:

The patient died of cerebral hernia due to intracranial hypertension in the eighth week of the disease.

Conclusions:

PCNS ALK-1-positive anaplastic large cell lymphoma is extremely rare. Also, it is difficult to distinguish from central meningeal lymphoma and central nervous system infection, which might lead to delayed diagnosis. However, early diagnosis depends on the pathological diagnosis of brain tissue biopsy.
Traditional Chinese herbal bath therapy for insomnia
Authors: Wen Qiao , Dong Xiaohui , Lan Lei , Liu Lizhou , Tumilty Steve , Yan Bohua , Chen Yabing , Wang Xing , Zhang Yonggang , Feng Fen
Published: July 2020

Introduction:

Insomnia is a major public health problem. Due to the side effects of pharmacological therapy, people are seeking to choose complementary and alternative therapies for insomnia disorder. Traditional Chinese herbal bath therapy is an important complementary therapy which combines advantages of Chinese herbs and bathing therapy. This protocol describes the methodology of a systematic review assessing the effectiveness and safety of traditional Chinese herbal bath therapy for insomnia.

Methods and analysis:

Reporting of this review will be adherent to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We will electronically search the following seven databases from inception to January 23, 2020: PubMed, Cochrane database (CENTRAL), EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Database, and Wanfang Database. Parallel randomized controlled trials evaluating the effectiveness and safety of traditional Chinese herbal bath therapy for insomnia will be included. Study selection, data extraction and assessment of risk of bias will be performed independently by two researchers. The sleep quality will be assessed as the primary outcome. Global symptom improvement, anxiety and depression, and adverse events will be evaluated as secondary outcomes. The Cochrane's risk of bias tool will be utilized for assessing the methodological quality of included studies. Revman software (v.5.3) will be used for data synthesis and statistical analysis. Data will be synthesized by either fixed-effects or random-effects model according to a heterogeneity test. If it is not appropriate for a meta-analysis, a descriptive analysis will be conducted. GRADE system will be used to assess the quality of evidence.

PROSPERO registration number:

CRD42020168507
Multiple limb compartment syndrome as a manifestation of capillary leak syndrome secondary to metformin and dipeptidyl peptidase IV inhibitor overdose
Authors: Kasugai Daisuke , Tajima Kosuke , Jingushi Naruhiro , Uenishi Norimichi , Hirakawa Akihiko
Published: July 2020

Rationale:

Capillary leak syndrome is a condition that increases systemic capillary permeability and causes characteristic manifestations such as recurrent hypovolemia, systemic edema, and hemoconcentration. Acute limb compartment syndrome is a possible complication of severe capillary leak syndrome. However, timely diagnosis and prompt treatment are challenging because of atypical presentation.

Patient concerns:

An 18-year-old woman with a history of clinical depression was admitted to our intensive care unit (ICU) because of metformin and vildagliptin overdose. She developed marked vasodilatory shock with recurrent severe hypovolemia and disseminated intravascular coagulation. After urgent hemodialysis and plasma exchange, she started to stabilize hemodynamically. However, her limbs became stone-hard with massive edema. Her serum creatinine kinase level increased to an extremely high level.

Diagnosis:

Extremities were distended, and her skin developed pallor with blistering. Intramuscular pressure in both forearms and lower legs was significantly elevated.

Interventions:

Decompressive fasciotomy was performed. Hemodialysis was continued because of rhabdomyolyses-induced acute kidney injury.

Outcomes:

The patient was finally able to walk by herself at the time of hospital discharge on day 109.

Lessons:

The possibility of acute compartment syndrome should be considered in patients with marked capillary leakage, especially after aggressive fluid resuscitation. It is important to be aware of the compartment syndrome in an ICU setting because communication barriers often mask typical symptoms and make diagnosis difficult.
Very late relapse of high-grade osteosarcoma
Authors: Kaneuchi Yoichi , Hakozaki Michiyuki , Yamada Hitoshi , Hasegawa Osamu , Yamada Shoki , Oka Yuka , Watanabe Kazuo , Konno Shinichi
Published: July 2020

Rationale:

Osteosarcoma is the most common primary malignant bone tumor in children. The prognosis of osteosarcoma has improved with the use of aggressive systemic chemotherapy in addition to surgery. The relapse of osteosarcomas is usually as lung metastasis observed within 2 to 3 years after the initial treatment. A relapse is rarely observed at >10 years.

Patient concerns:

We report the case of a 51-year-old Japanese man who was treated for high-grade osteosarcoma of the femur at 13 years old. He was referred to our hospital with a suspicion of primary lung cancer based on back pain, respiratory distress, and an abnormal mass on chest radiograph.

Diagnoses:

Computed tomography-guided biopsy confirmed the lung lesion as a metastatic recurrence of high-grade osteosarcoma without local recurrence.

Interventions:

Chemotherapy was planned, but the patient's general condition rapidly deteriorated and thus palliative therapy was provided.

Outcomes:

The patient died 2 months after the initial consultation.

Lessons:

The survival durations of osteosarcoma patients have been prolonged by recent progress in multimodality therapy, and thus clinicians as well as osteosarcoma patients should always keep in mind the possibility of very late relapse.
Penile metastasis in rectal cancer with pathologic complete response after neoadjuvant chemoradiotherapy
Authors: Lee Taek-Gu , Son Seung-Myoung , Kim Myung Jo , Lee Sang-Jeon
Published: July 2020

Rationale:

Penile metastasis in rectal cancer is very rare and often originates from prostatic or bladder cancer. The prognosis of penile metastasis is poor and its treatments are more often palliative than curative due to association with disseminated metastases. Pathologic complete response (pCR) in rectal cancer with neoadjuvant chemoradiotherapy (CRT) has been shown to be surrogate marker of favorable long-term outcomes and currently has no report of penile metastasis. Here, we first report isolated penile metastasis in rectal cancer with pCR after neoadjuvant CRT.

Patient concern:

The patient was a 74-year-old male with metastasis to the glans penis from rectal cancer diagnosed 9 months after abdominoperineal resection. Physical examination revealed palpable multiple nodules on the glans penis.

Diagnosis:

Penile biopsy revealed metastatic carcinoma from the rectal cancer.

Intervention:

Chemotherapy was started as soon as possible, because patient suffered urinary discomfort by rapid growing metastatic lesions. He is currently receiving palliative chemotherapy with modified FOLFOX-6 (mFOLFOX-6; oxaliplatin with 5-fluorouracil and folinic acid) plus bevacizumab.

Outcome:

The patient is still alive 4 months after diagnosis with markedly decreased metastatic lesions.

Lesson:

We propose that although penile metastasis in rectal cancer with pCR after preoperative neoadjuvant CRT is extremely rare, it might help to start early palliative chemotherapy and clinicians should be aware of this possibility.
Clinical outcomes following polymer-free sirolimus-eluting stent implantations in unselected patients
Authors: Krackhardt Florian , Waliszewski Matthias W. , Kherad Behrouz , Barth Claudia , Marcelli Daniele
Published: July 2020

Patients with chronic kidney disease (CKD are frequently excluded from coronary artery disease trials. The aim of this assessment was to study the clinical outcomes of polymer-free sirolimus-eluting stent implantations in patients with impaired renal function.

Large-scale, international, single-armed, multicenter, ‘all comers’ observational studies (ClinicalTrials.gov Identifier: NCT02629575 and NCT02905214) were used for this post-hoc subgroup analysis to compare the clinical outcomes in patients with normal renal function (NRF) to those with renal insufficiency (CKD, dialysis dependence). The accumulated target lesion revascularization rate was the primary endpoint at 9 to 12 months whereas the accumulated major adverse cardiac event, stent thrombosis (ST) and procedural success rates were part of the secondary endpoints.

There were 6791 patients with NRF, whereas 369 patients had CKD and 83 patients were dialysis dependent. The target lesion revascularization rate at 9 to 12 months was significantly higher in dialysis patients (2.1% vs 3.3% vs 6.7%, P = .011). The accumulated major adverse cardiac events rates in the dialysis and in the CKD group were significantly higher as compared to patients with NRF (13.3% vs 4.0%, P < .001; 6.5% vs 4.0%, P = .024). Finally, ST rates (NRF: 0.7%, CKD: 0.6%, dialysis: 1.3%) were not statistically different between subgroups (P = .768). All-cause cumulative mortality rates were 3.3% (CKD) and 4.0% (dialysis) respectively.

Percutaneous coronary interventions with polymer-free, ultra-thin strut sirolimus-eluting stents have comparable revascularization rates in CKD and dialysis dependent patients as compared to percutaneous coronary interventions with other 2nd generation drug-eluting stents. ST and all-cause mortality rates were low as compared to available literature references.
Operative vs conservative treatment in distal radius fractures
Authors: Wu Meng , Li Xiongfeng , Li Jianyou , Chen Yonghua
Published: July 2020

Background:

Given this lack of conclusive outcome data, there are currently no clear guidelines to direct the treatment of displaced distal radius fractures in the elderly. This retrospective clinical trial was performed to compare the outcomes of two methods that were used for the treatment of displaced and unstable distal radial fractures in patients 65 years of age or older:

Methods:

This study was performed and reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology checklist. Between January 2017 and May 2018, a total of 184 patients who presented to Huzhou Traditional Chinese Medicine Hospital with distal radius fractures were extracted from the hospital database and evaluated for eligibility. This retrospective cohort study was approved by the institutional review board in our hospital. Outcome measures included Patient-Related Wrist Evaluation score, patient satisfaction, complications, and radiographic outcomes. SPSS software package (version 21.0; SPSS Inc, Chicago, IL) was used for all statistical analyses.

Results:

The hypothesis was that the two groups would achieve similar functional scores and complications in distal radial fractures.

Trial registration:

This study protocol was registered in Research Registry (researchregistry5689).
Predictors of all-cause 1-year mortality in myocardial infarction patients
Authors: Ye Qing , Zhang Jie , Ma Likun
Published: July 2020

Compared with the general population, myocardial infarction (MI) survivors have a higher risk of mortality in the first year after the index event.

The aim of this study was to determine the associations between variables obtained during the index admission and 1-year all-cause mortality on follow-up.

A cohort of 296 patients was enrolled in the study, with a median age of 63.8 ± 12.68 years. All patients received a coronary angiography and stent implantation by percutaneous coronary intervention. Each variable was tested for association with all-cause mortality, using chi-square tests for categorical and binary variables and t tests for continuous variables. The relative prognostic power of each significant variable was further evaluated by logistic regression before and after adjustment for differences in baseline characteristics.

Patients who were deceased after 1-year of MI had significantly higher mean age, increased prevalence of diabetes, and elevated heart rate as compared to those who were surviving. Univariate analysis indicated that patient mortality within 1-year of MI was strongly correlated with higher rates of pump failure on admission (P < .0001), bleeding complications (P = .02), the severity of coronary artery disease measured by Gensini score (P = .04), and decreased left ventricular ejection fraction (LVEF) (P < .0001). After adjustment of baseline variables, only pump failure (P = .006) and reduced LVEF (P < .0001) were independently associated with 1-year mortality.

Our study shows that LVEF dysfunction and pump failure are independent predictors of 1-year all-cause post-MI mortality, while the severity of coronary artery disease and bleeding did not qualify as independent predictors. Also, age, history of diabetes, and elevated heart rate may be used as markers for increased mortality rates.
Computed tomography-negative symptomatic intracerebral hemorrhage in a patient with cerebral small vessel disease
Authors: Han Jinhee , Yang Harin , Bae Jeong Hoon , Kim Hyun Young , Kim Young Seo
Published: July 2020

Rationale:

Computed tomography plays a key role in the initial evaluation of suspected acute stroke by ruling out the possibility of hemorrhage before thrombolysis. Recently, many reports have described cases of symptomatic microbleeds, and there may also have been a case of computed tomography- negative intracerebral hemorrhage.

Patient concerns:

A 70-year-old female patient who had a history of lacunar infarction and severe small vessel disease developed dysarthria. On brain non-contrast computed tomography there was no evidence of intracerebral hemorrhage. However, brain magnetic resonance imaging performed at 3 hours after the initial computed tomography showed cerebral hemorrhage.

Diagnoses:

The diagnosis was computed tomography-negative intracerebral hemorrhage.

Interventions:

The patient was treated with cilostazole 100 mg twice a day with blood pressure management.

Outcomes:

The dysarthria was fully recovered within 5 days and the patient did not suffer recurrent stroke symptoms over the following 2 years.

Lessons:

In patients with underlying severe small vessel disease and microbleeds, there could be computed tomography-negative hemorrhage and susceptibility weighted magnetic resonance image could be needed. More attention is required before applying thrombolysis therapy because there is a possibility of cerebral hemorrhage in those patients.
Progressive worsening of the respiratory and gut microbiome in children during the first two months of COVID-19
Authors: Xu Rong , Liu Pengcheng , Zhang Tao , Wu Qunfu , Zeng Mei , Ma Yingying , Jin Xia , Xu Jin , Zhang Zhigang , Zhang Chiyu
Published: July 2020

Children are less susceptible to COVID-19 and manifests lower morbidity and mortality after infection, for which a multitude of mechanisms may be proposed. Whether the normal development of gut-airway microbiome is affected by COVID-19 has not been evaluated. We demonstrate that COVID-19 alters the respiratory and gut microbiome of children. Alteration of the microbiome was divergent between the respiratory tract and gut, albeit the dysbiosis was dominated by genus Pseudomonas and sustained for up to 25-58 days in different individuals. The respiratory microbiome distortion persisted in 7/8 children for at least 19-24 days after discharge from the hospital. The gut microbiota showed early dysbiosis towards later restoration in some children, but not others. Disturbed development of both gut and respiratory microbiomes, and prolonged respiratory dysbiosis in children imply possible long-term complications after clinical recovery from COVID-19, such as predisposition to an increased health risk in the post-COVID-19 era.
Genomic epidemiology of the early stages of SARS-CoV-2 outbreak in Russia
Authors: Komissarov Andrey B. , Safina Ksenia R. , Garushyants Sofya K. , Fadeev Artem V. , Sergeeva Mariia V. , Ivanova Anna A. , Danilenko Daria M. , Lioznov Dmitry , Shneider Olga V. , Shvyrev Nikita , Spirin Vadim , Glyzin Dmitry , Shchur Vladimir , Bazykin Georgii A
Published: July 2020

The ongoing pandemic of SARS-CoV-2 presents novel challenges and opportunities for the use of phylogenetics to understand and control its spread. Here, we analyze the emergence of SARS-CoV-2 in Russia in March and April 2020. Combining phylogeographic analysis with travel history data, we estimate that the sampled viral diversity has originated from 67 closely timed introductions into Russia, mostly in late February to early March. All but one of these introductions came from non-Chinese sources, suggesting that border closure with China has helped delay establishment of SARS-CoV-2 in Russia. These introductions resulted in at least 9 distinct Russian lineages corresponding to domestic transmission. A notable transmission cluster corresponded to a nosocomial outbreak at the Vreden hospital in Saint Petersburg; phylodynamic analysis of this cluster reveals multiple (2-4) introductions each giving rise to a large number of cases, with a high initial effective reproduction number of 3.7 (2.5-5.0).