bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the WHO ICTRP for novel coronavirus clinical trial registrations
Authors: Song Gao , Cheng Meng Qun , Wei Xian Wen
Published: October 2020

Up-to-date information on the current progress made in the research and development to control the global COVID-19 pandemic is important. The study aimed to analyze the clinical trial characteristics and vaccine development progress of the new Coronavirus Disease 2019 (COVID-19) registered with the World Health Organization International Clinical Trial Registry Platform (WHO ICTRP).

A comprehensive search of COVID-19 clinical trials since the establishment of the ICTRP to June 11, 2020, was conducted to record and analyze relevant characteristics. Chi-Squared test was used to compare the statistical differences between different research types, interventions, and sources.

A total of 3282 COVID-19 clinical trials in 17 clinical trial registration centers were registered with the WHO ICTRP. The main research sources for the present study were ClinicalTrials.gov and ChiCTR. There were significant differences in the parameters of study location (P = .000), number of participants (P = .000), study duration (P = .001), research stage (P = .000), randomization procedure (P = .000), and blinding method (P = .000) between the 2 registration sources. There were significant differences in all the parameters between different kinds of intervention methods. Hydroxychloroquine, plasma therapy, and Xiyanping injection were the high-frequency research drugs used. Ten different vaccine studies were registered under phases I-II.

Amongst the studies researched, heterogeneity existed for various parameters. Differences in the type of study, interventions, and registration sources of the studies led to significant differences in certain parameters of the COVID-19 clinical trials. The statistics of high-frequency drugs and the progress of vaccine trials may provide an informative reference for the prevention and control of COVID-19.
A comparison between laparoscopy and hysteroscopy approach in treatment of cesarean scar pregnancy
Authors: Zhang Xiaolei , Pang Yingxin , Ma Yanhui , Liu Xin , Cheng Lin , Ban Yanli , Cui Baoxia
Published: October 2020

The aim of the study was to compare the efficacy of laparoscopy and hysteroscopy for the treatment of cesarean scar pregnancy (CSP) and analyze the clinical factors associated with successful selection for hysteroscopic or laparoscopic treatment of CSP.

We retrospectively studied 112 cases of CSP that were treated by laparoscopy and/or hysteroscopy in our hospital from December 2014 to December 2017. In total, 72 of these patients underwent ultrasound-guided curettage and hysteroscopic resection without uterine scar defect repair. Fourty of these patients underwent laparoscopic resection and repair of the uterine scar defect. We analyzed the different clinical variables between the 2 groups and identified the clinical factors which could predict the need for the laparoscopic repair of uterine scar defect. Results showed that laparoscopy and hysteroscopy were safe ways to treat CSP, and no patient underwent hysterectomy. The β-hCG level in both of the 2 groups decreased to normal 4 to 8 weeks after surgery. There were significant differences between the hysteroscopy group and laparoscopy uterine scar repair group in terms of days of amenorrhea, gestational sac diameter, myometrial thickness, operation time, intraoperative blood loss, and hospitalization duration (P < .05). Logistic regression analysis showed that the days of amenorrhea, gestational sac diameter and myometrial thickness were independent risk factors for CSP treated by minimally invasive surgery, which were also shown by ROC curve analysis to be predictors of the need for the repair of the uterine scar defect, with optimal cutoffs of 52.50 days, 3.25 cm, and 2.05 mm, respectively; and the areas under their corresponding ROC were 0.721, 0.851, and 0.927, respectively.

We conclude that laparoscopy and hysteroscopy are safe and efficient minimally invasive procedures for the treatment of CSP. The days of amenorrhea, gestational sac diameter and myometrial thickness may be key factors associated with successful selection for hysteroscopic or laparoscopic treatment of CSP.
Clinical characteristics, mortality, and prognostic factors for bullous pemphigoid in a Thai population
Authors: Amonchaisakda Nuntouchaporn , Aiempanakit Kumpol
Published: October 2020

Bullous pemphigoid is an uncommon, autoimmune, blistering disease. Clinical features, associated conditions, and outcomes differ according to country. We aimed to determine the mortality rate and clinical characteristics of Thai patients and to evaluate the risk factors associated with survival.

A retrospective analysis was conducted on 119 patients, over a ten-year period, at Songklanagarind Hospital, the largest tertiary university hospital in Southern Thailand.

The median age of onset was 82 years [interquartile range 72, 90], and 60 (50.4%) patients were men. The underlying diseases were hypertension (53.8%), neurological disease (42.8%), and diabetes mellitus (31.9%). Fifty-eight patients (48.7%) experienced pruritus, and 61.3% of patients had mild cutaneous lesions (less than 10% of the body surface area) on the day of diagnosis. Nine percent of patients presented with mucosal involvement. Complete blood counts showed anemia (32.8%), neutrophilia (30.3%), and eosinophilia (42.9%). The 1-, 3- and 5-year overall mortality rates were 28.1% [95% confidence interval (CI), 7.8–36.6], 55.7% (95% CI, 44.4–64.7) and 71.9% (95% CI 59.9–80.2), respectively. On multivariate analysis, high neutrophil/lymphocyte ratio [odds ratio (OR) 5.55, P < .001] and anemia (OR 2.93, P = .025) were found to be independently associated with mortality rate, whereas disease remission (OR 0.25, P = .003) was demonstrated to be a good prognostic factor.

This is the first study to analyze the mortality rate of Bullous pemphigoid in Thailand. Mortality was associated with high neutrophil/lymphocyte ratio and anemia.
Efficacy of afatinib for pulmonary adenocarcinoma with leptomeningeal metastases harboring an epidermal growth factor receptor complex mutation (exon 19del+K754E)
Authors: Ma Chunhua , Liu Mei , Mu Ning , Li Jinduo , Li Lin , Jiang Rong
Published: October 2020

Rationale:

Liquid biopsy of cerebrospinal fluid (CSF) and sequencing of cell-free DNA has rarely been used to identify epidermal growth factor receptor (EGFR) mutations, which can guide the design of precise, personalized treatment for patients with leptomeningeal metastasis from lung adenocarcinoma.

Patient concerns:

A 42-year-old woman with lung adenocarcinoma and leptomeningeal metastasis was admitted to our hospital on March 31, 2019. She exhibited no response to treatment with gefitinib, osimertinib, or chemoradiotherapy and was in critical condition, with an expected survival of <4 weeks.

Diagnosis:

Next-generation sequencing of CSF and peripheral blood samples identified an EGFR complex mutation (exon19del+K754E).

Interventions:

On April 10, 2019, the patient started oral afatinib (40 mg po qd), but she developed a grade III oral mucosal reaction 1 week later. The afatinib dose was reduced to 30 mg po qd.

Outcomes:

At the follow-up examination on May 15, 2019, the patient reported relief from headaches. Enhanced magnetic resonance imaging revealed a reduction in abnormal leptomeningeal enhancement, and the CSF pressure and carcinoembryonic antigen levels were also reduced. The patient continued to respond to afatinib treatment (30 mg once daily) with minimal adverse effects.

Lessons:

This is the first case report of clinical improvement after afatinib treatment in a patient with lung adenocarcinoma and leptomeningeal metastasis harboring an EGFR complex mutation (exon19del+K754E), and thus provides a clinical reference for treatment with afatinib of cancers harboring EGFR compound mutations.
Potential novel proteomic biomarkers for diagnosis of vertebral osteomyelitis identified using an immunomics protein array technique
Authors: Chen Chang-Hua , Chang Ing-Lin , Wang Shu-Hui , Yen Hua-Cheng , Lin Jen-Shiou , Lo Shou-Chen , Huang Chieh-Chen
Published: October 2020

Rationale:

Although vertebral osteomyelitis (VO) is commonly associated with high morbidity and high recurrence rate, effective diagnostic and prognostic biomarkers of VO are still lacking.

Patients concerns:

Case 1: a 60-year-old male had had upper back pain for 3 days. Case 2: a 71-year-old female presented upper back pain for 2 days.

Diagnoses:

Based on physical examination and findings of magnetic resonance imaging and findings by matrix-assisted laser desorption ionization-time of flight mass spectrometry, they were diagnosed with Staphylococcus aureus VO.

Interventions:

Using Sengenics ImmunomeTM Protein Array by analyzing autoantibodies in both VO patients, potential biomarkers of VO were explored.

Outcomes:

Four subjects with more than 1600 antigens screened while the results showed that 14-3-3 protein gamma, pterin-4-alpha-carbinolamine dehydratase, fructose-bisphosphate aldolase A, and keratin type II cytoskeletal 8 were highly differentially expressed among VO and controls. Relevant auto-antibody profiles were discovered after intra-group and inter-group comparison, and based on functional rationality, an adapter protein 14-3-3 protein gamma, and pterin-4-alpha-carbinolamine dehydratase that involved in tetrahydrobiopterin biosynthesis, might serve as valuable diagnostic biomarkers.

Lessons:

This pilot study on 4 subjects with more than 1600 antigens screened on the Sengenics Immunome protein array provided a general outlook on autoantibody biomarker profiles of VO subjects. Future large-scale trials with longer follow-up times are warranted.
Moxibustion combined with characteristic lifestyle intervention of Traditional Chinese Medicine in the treatment of abdominal obesity
Authors: Wang Li-Hua , Huang Wei , Zhou Wei , Zhou Li , Zhou Xiao-Li , Zhou Peng , Yan Yan , Zhou Zhong-Yu , Wang Hua
Published: October 2020

Background:

Abdominal obesity occurs when excessive visceral and subcutaneous fat is built up around the abdomen and stomach, which negatively impacts human health. Moxibustion, arose from Traditional Chinese Medicine (TCM), has been widely applied in the treatment of abdominal obesity. Several studies have shown the positive effects of moxibustion in prevention and treatment of endocrine issues and excess body weight. In this context, our study aims to examine the safety and efficacy of the combination of moxibustion and characteristic lifestyle intervention of TCM in the treatment of abdominal obesity.

Methods/design:

This study will be a multicenter, randomized, controlled trial conducted from September 2020 to January 2022 that includes 150 participants who have abdominal obesity and meet the eligibility criteria. The participants will be randomly divided into 3 groups in a 2:2:1 allocation ratio. The intervention group will receive moxibustion combined with characteristic lifestyle intervention of TCM; the other group will receive moxibustion combined with lifestyle intervention; the control group will receive lifestyle intervention only. Eight-week moxibustion sessions will be provided to participants assigned to the 2 intervention groups. The characteristic lifestyle intervention of TCM will also last 8 weeks, whereas the lifestyle intervention will last 12 weeks including 8-week treatment period, 4-week follow-up period. The primary outcome is the waist circumference measured by a tape measure. The secondary outcomes include obesity-related indicators, serum biochemical indexs, blood pressure, conversion score of physical symptoms, and measurement of the scale. Adverse events will be recorded during the treatment and follow-up period.

Discussion:

The results are expected to provide clinical evidence for the application of the combination of moxibustion and characteristic lifestyle intervention of TCM in patients with abdominal obesity.

Trial registration:

ClinicalTrials.gov, NCT04501198, Registered on 9 June 2020.
Local functional connectivity of patients with acute and remitting multiple sclerosis
Authors: Zhu Yanyan , Huang Muhua , Zhao Yanlin , Pei Yixiu , Wang Yao , Wang Lei , He Ting , Zhou Fuqing , Zeng Xianjun
Published: October 2020

Using Kendall's coefficient of concordance (KCC-) and Coherence (Cohe-) regional homogeneity (ReHo) to explore the alterations of brain local functional connectivity in acute and remitting relapsing-remitting multiple sclerosis (RRMS), and its clinical relevance.

18 acute RRMS, 26 remitting RRMS and 20 healthy controls received resting-state functional magnetic resonance imaging scanning. After data preprocessing and ReHo (KCC-ReHo and Cohe-ReHo) calculation, analysis of variance and followed post hoc analysis was used to compare the KCC-ReHo or Cohe ReHo maps across groups.

After analysis of variance analysis, regions with significant among-group differences detected by the 2 ReHo analysis were overlapped, these overlapped regions located in the left superior frontal gyrus (SFG), right SFG, left cuneus and right middle occipital gyrus (P < .01, Gaussian random field theory correction). Followed post hoc tests showed that, compared with healthy controls,

Both acute and remitting RRMS patients has disease-related brain dysfunction, interestingly, relative to remitting RRMS, the acute RRMS patients mobilized more brain regions involving visual information processing in an attempt to maintain functional stability. In addition, our results also provide a methodological consideration for future ReHo analysis.
Shengyang Yiwei Decoction for the treatment of chronic gastritis
Authors: Xiong Min , Luo Huan , Zhu Wenyu , Shen Tao
Published: October 2020

Background:

Chronic gastritis is a very common chronic gastric mucosal inflammatory disease in China. Long-term chronic inflammation will aggravate the disease and develop towards gastric cancer. Clinically, infection with Helicobacter pylori (H pylori) is a common cause. The application of antibiotics to eradicate H pylori has been reported to have produced drug resistance. However, the application of Shengyang Yiwei Decoction(SYD) in traditional Chinese medicine has resulted in significant clinical effects and small side effects. It is used for the treatment of chronic gastritis and other diseases, but there is a lack of systematic reviews on the treatment of chronic gastritis by SYD. This article reviews the efficacy and safety of SYD in the treatment of chronic gastritis.

Methods:

The registration date for the randomized controlled trials is set by the database to October 15, 2020. Through searching the following 8 Chinese and English electronic databases: Cochrane Library, Embase, PubMed, Science Net, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Science Journal Database and Wanfang Database to analyze. The main results were clinical efficacy, H pylori infection clearance rate, symptom score and quality of life, and 1-year recurrence rate. Finally, Stata 15 was used for meta-analysis.

Results:

This study will provide the latest evidence for the treatment of chronic gastritis by SYD in the following aspects: clinical efficacy, H pylori infection clearance rate, quality of life, symptom score, and 1-year recurrence rate.

Conclusion:

The results of this study will provide evidence for evaluating the effectiveness of SYD in chronic gastritis treatment.

OSF registration number:

DOI 10.17605/OSF.IO/AZKUQ
Effects of dexamethasone in traumatic brain injury patients with pericontusional vasogenic edema
Authors: Moll Apolonia , Lara Mónica , Pomar Jaume , Orozco Mónica , Frontera Guiem , Llompart-Pou Juan A. , Moratinos Lesmes , González Víctor , Ibáñez Javier , Pérez-Bárcena Jon
Published: October 2020

Cerebral edema is a frequent and serious complication in traumatic brain injury (TBI) patients. The objective is to study the effect of dexamethasone in patients with brain contusions, and to assess its effect on the vasogenic component of the pericontusional edema.

Prospective-observational study to quantify, using magnetic resonance imaging, the volume of the edema before and after 10 days of dexamethasone in patients with brain contusions. Using diffusion tensor imaging, we have examined the effect of dexamethasone on fractional anisotropy (FA) and apparent diffusion coefficient (ADC). To assess changes, the pre- and post-treatment values for each patient were compared using a paired-samples Student t test.

We included 30 TBI patients, 15 in each group. The volume of the vasogenic edema in the group of patients treated with dexamethasone decreased from 22 to 19 mL and this decrease was statistically significant (P < .05). Nevertheless, in the non-steroids group the volume of the vasogenic edema increased from 11 to 15 mL. There was a significant decrease in the ADC value (from 1.78–1.59; P < .05); and a significant increase in the FA value (0.09–0.11; P < .05) in the patients treated with dexamethasone.

Using diffusion tensor imaging we have shown in a selected group of TBI patients with vasogenic pericontusional edema, a reduction of edema volume, a decrease in the ADC and an increase in the FA after treatment with dexamethasone. However, we have no data if such results are beneficial in terms of improving functional outcome.
Path analysis of the effects of social support, self-efficacy, and coping style on psychological stress in children with malignant tumor during treatment
Authors: Liu Qian , Mo Lin , Huang Xianqiao , Yu Lu , Liu Yang
Published: October 2020

The aim of this study was to explore the relationship between social support, self-efficacy, coping style, and psychological stress in children with malignant tumors during the treatment, and to clarify the mediating effects.

From May 2019 to August 2019, selected by convenience sampling method, 141 children with malignant tumors in the treatment period were evaluated using the Social Support Questionnaire, General Self-efficacy Scale, Simplified Coping Style Questionnaire, and Depression-Anxiety-Stress Scale.

The results of correlation analysis showed that depression was negatively correlated with coping style, self-efficacy, affirmation and support, satisfaction, company, and intimacy, but positively correlated with conflict and punishment; both anxiety and stress were significantly negatively correlated with coping style, self-efficacy, affirmation and support, company, and intimacy. The results of the model indicated that gender, social support, self-efficacy, and coping style could directly predict the psychological stress of children with malignant tumors in the treatment period, social support and self-efficacy could indirectly predict the psychological stress of children with malignant tumors, and the total effect of self-efficacy on the psychological stress of children was the largest. Through 2000 bootstrap tests of mediating effect, it not only confirmed the mediating effect of self-efficacy and coping style but also had a chain-mediating effect.

Appropriate social support can improve the self-efficacy of children with malignant tumors in the treatment period and encourage them to take a positive response to the disease, thereby effectively preventing or reducing the occurrence of psychological stress.
Comparison between anteroposterior and oblique “Scotty dog” approach during S1 transforaminal epidural steroid injection
Authors: Kang Ryung A. , Sim Woo Seog , Choi Ji Won , Kang Sehee , Lee Seungwon , Jee Hyeon Sook , Oh Eun Jung , Kim Yunghun , Ko Justin Sangwook
Published: October 2020

Background:

Traditionally, S1 transforaminal epidural steroid injection (TFESI) has been performed using an anteroposterior (AP) fluoroscopic view. In 2007, the oblique “Scotty dog” (OS) approach was introduced as an alternative technique. We compared passage time of the needle into S1 foramen (Tf) between the anteroposterior (AP) and oblique “Scotty dog” (OS) approach during S1 TFESI.

Methods:

In this prospective randomized controlled trial, seventy patients scheduled S1 TFESI were randomly allocated into AP or OS groups. In the AP group, a slight cephalad-caudad tilt was used. In the OS group, the C-arm was rotated ipsilateral oblique degrees to view the S1 Scotty dog. Both groups received injection of steroid mixed with local anesthetics. We measured the passage time of the needle into S1 foramen (Tf), primary outcome, and total procedure time (Tt) between the groups. We also recorded presence of intravascular injection, patients-assessed pain relief for one month and complications.

Results:

The Tf and Tt were shorter in the OS than in the AP group (24.4 ± 24.0 s vs 47. 8 ± 53.2seconds; 93.3 ± 35.0 seconds vs 160.0 ± 98.7 seconds, P < .001, both). Incidence of intravascular injection (AP, 8 [22.8%]; OS, 4 [11.4%], P = .205), pain score, and complication rates were not statistically different between the two groups. In logistic regression analysis, the body mass index (BMI) was a risk factor for longer Tt (odds ratio [OR] = 1.27, 95% CI: 1.02–1.58, P = .030).

Conclusion:

The passage time of the needle into S1 foramen was shorter in OS approach and the OS approach reduced the procedure time compared with the AP approach during S1 TFESI. The practitioners should note that procedure time can be prolonged in obese patients.
Cross-sectional investigation of serum creatine kinase concentration in Graves disease patients treated with oral antithyroid drugs
Authors: Cheng Ying , Sun Zhiyong , Zhong Dapeng , Ren Li , Yang Hang
Published: October 2020

Elevated serum creatine kinase (CK) concentration was reported in some Graves disease patients during the treatment with oral antithyroid drugs (ATD). The pathogenesis of this abnormal biochemical value was considered to be related to the therapeutic drug. However, the relevant epidemiological investigation was absent.

Overall, 416 patients with Graves disease treated with oral ATDs were recruited from December 2017 to October 2019. Clinical characteristics such as the patient's medical history and therapeutic regimen were collected. Serum CK concentration and thyroid function were measured. Statistical analysis was adopted to clarify the relationship between serum CK level and these clinical parameters.

Elevation of serum CK concentration was emerged in 13.5% patients who were treated with oral ATDs. The proportion was significantly higher among men than among women (19.5% vs 10.8%). There was no correlation between increased serum CK concentration and age. More than 60% of serum CK elevations occurred within 6 months after taking oral ATDs. Free triiodothyronine and free thyroxine are negatively correlated with serum CK concentration. The correlation coefficients are respectively –0.222 (P < .05) and –0.234 (P < .05). There is positive correlation between thyroid stimulating hormone and serum CK concentration. The correlation coefficient is 0.405 (P < .05). There was no statistical correlation between drug dosage and increased serum CK level.

Increased serum CK level is a common adverse reaction of oral ATDs. It generally develops early after starting treatment. The cause of this adverse reaction is not clear. It is speculated that elevation of serum CK level is related to the fluctuation of thyroid function.
Hyperacute extensive spinal cord infarction and negative spine magnetic resonance imaging: a case report and review of the literature
Authors: Costamagna Gianluca , Meneri Megi , Abati Elena , Brusa Roberta , Velardo Daniele , Gagliardi Delia , Mauri Eleonora , Cinnante Claudia , Bresolin Nereo , Comi Giacomo , Corti Stefania , Faravelli Irene
Published: October 2020

Rationale:

Spinal cord infarction (SCI) accounts for only 1% to 2% of all ischemic strokes and 5% to 8% of acute myelopathies. Magnetic resonance imaging (MRI) holds a role in ruling out non-ischemic etiologies, but the diagnostic accuracy of this procedure may be low in confirming the diagnosis, even when extensive cord lesions are present. Indeed, T2 changes on MRI can develop over hours to days, thus accounting for the low sensitivity in the hyperacute setting (ie, within 6 hours from symptom onset). For these reasons, SCI remains a clinical diagnosis. Despite extensive diagnostic work-up, up to 20% to 40% of SCI cases are classified as cryptogenic. Here, we describe a case of cryptogenic longitudinally extensive transverse myelopathy due to SCI, with negative MRI and diffusion-weighted imaging at 9 hours after symptom onset.

Patient concerns:

A 51-year-old woman presented to our Emergency Department with acute severe abdominal pain, nausea, vomiting, sudden-onset of bilateral leg weakness with diffuse sensory loss, and paresthesias on the trunk and legs.

Diagnoses:

On neurological examination, she showed severe paraparesis and a D6 sensory level. A 3T spinal cord MRI with gadolinium performed at 9 hours after symptom onset did not detect spinal cord alterations. Due to the persistence of a clinical picture suggestive of an acute myelopathy, a 3T MRI of the spine was repeated after 72 hours showing a hyperintense “pencil-like” signal mainly involving the grey matter from T1 to T6 on T2 sequence, mildly hypointense on T1 and with restricted diffusion.

Interventions:

The patient was given salicylic acid (100 mg/d), prophylactic low-molecular-weight heparin, and began neuromotor rehabilitation.

Outcomes:

Two months later, a follow-up neurological examination revealed a severe spastic paraparesis, no evident sensory level, and poor sphincteric control with distended bladder.

Lessons:

Regardless of its relatively low frequency in the general population, SCI should be suspected in every patient presenting with acute and progressive myelopathic symptoms, even in the absence of vascular risk factors. Thus, a clinical presentation consistent with a potential vascular syndrome involving the spinal cord overrides an initially negative MRI and should not delay timely and appropriate management.
Is it coincidental or correlative between reversible splenial lesion syndrome and atrial septal defect?
Authors: Li Jiangang , Chen Yingcong , Liu Jianxue , Mai Xingsheng , Jing Shaohua
Published: October 2020

Rationale:

Reversible splenial lesion syndrome (RESLES) is a recently identified clinico-radiological syndrome, the etiology is miscellaneous. Atrial septal defect (ASD) as an underlying etiology for RESLES has not been reported. We first report a rare case of RESLES associated with ASD. The clinical, radiological, and ultrasonic profiles were presented and the pathophysiological mechanism was analyzed.

Patient concerns:

A 23-year-old man presented with headache, drowsiness, occasional paraphasia, and paroxysmal dry cough. Brain magnetic resonance imaging (MRI) on admission showed an ovoid isolated lesion in the splenium of corpus callosum, which exhibited hyperintensity on diffusion-weighted imaging and hypointensity on apparent diffusion coefficient, and completely disappeared on the follow-up MRI 14 days later. ASD was found by transthoracic echocardiography, Right-to-left shunts were detected on color Doppler of transesophageal echocardiography, and microemboli were captured by transcranial Doppler ultrasound.

Diagnoses:

According to his clinical history and imaging results, we confirmed the diagnosis of RESLES associated with ASD.

Interventions:

The patient was treated by oral aspirin and lopidogrel sulfate to inhibit platelet aggregation. In addition, oral nimodipine to suppress vasoconstriction.

Outcomes:

After 14 days treatment, all the symptoms presenting on admission resolved completely. Subsequently, a repair surgery of ASD under thoracoscopy was successfully performed.

Lessons:

To our knowledge, this is the first reported case of ASD may be an underlying etiology for RESLES and need require an etiotropic treatment.
Acquired hemophilia A in a woman with systemic lupus erythematosus
Authors: Shen Pan , Li Jing , Tu Shenghao , Chen Gang , Chen Chao
Published: October 2020

Rationale:

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies directed against the activity of factor VIII (FVIII) and presents with prolonged bleeding. 5.7% of systemic lupus erythematosus (SLE) patients are affected by AHA.

Patient concerns:

A 51-year-old female patient with SLE presenting with the fatigue and spontaneous clinical bleeding symptoms such as hematuria and ecchymoses for 1 week.

Diagnosis:

Laboratory examinations revealed prolongation of the activated partial thromboplastin time (APTT) (65.7 s), decreased FVIII activity (1.4%), and a titer of FVIII inhibitors of 8.5 Bethesda units/mL.

Interventions:

Transfusion of recombinant human FVIII (ADVATE) in combination with intravenous methylprednisolone, cyclophosphamide, plasmapheresis, and fresh frozen plasma successfully stopped the bleeding and reduced the level of FVIII inhibitor.

Outcomes:

The size of the hematoma slowly decreased. The skin ecchymosis was gradually absorbed, the hemoglobin count increased, and the coagulation index gradually improved. There was no new bleeding or bleeding site. The patient was discharged and transferred to a local hospital for hospice care.

Lessons:

AHA in a patient with SLE is rare. Once it occurs, it can be life-threatening. Clinicians should remain aware that because some cases of AHA may have features of SLE, appropriate distinction and diagnosis of these different but associated diseases is necessary.
Late-onset severe hepatic sinusoidal obstruction syndrome in an allogeneic stem cell transplant recipient
Authors: Sun Yan-ling , Liu Ling-ling , He Yi , Zhang Jing-wen , Wen Rui-juan , Yuan Qing , Wang Xin , Guo Ruo-mi , Li Xu-dong , Long Bing
Published: October 2020

Rationale:

Hepatic sinusoidal obstruction syndrome (SOS) is a rare and potentially fatal complications after hematopoietic stem cell transplantation (HSCT). Most severe SOS result in multi-organ dysfunction and are associated with a high mortality rate (>80%).

Patient concerns:

A 31-year-old man was diagnosed with chronic myeloid leukemia blast crisis. He presented with severe thrombocytopenia on day 42 post-HSCT (on days +42), gradually developed with painful hepatomegaly, ascites, and weight gain.

Diagnoses:

The abdominal computerized tomography showed hepatomegaly, hepatic congestion, periportal edema, narrow hepatic vein, and ascites suggestive of SOS/hepatic vein occlusion. According to the EBMT revised diagnostic criteria, the patient was diagnosed as late-onset severe SOS.

Interventions:

Comprehensive treatment including low molecular weight heparin was initiated.

Outcomes:

The patient had good response with resolution of his hepatomegaly, increase of platelet, weight and transaminase loss after 4 weeks treatment.

Lessons:

In SOS patients with nonspecific clinical and biochemical findings, computerized tomography scans can be useful in differentiating SOS from other complications after HSCT. low molecular weight heparin is effective for the treatment of SOS.
The combination of excimer laser ablation and drug eluting balloon for treating superficial femoral arterial occlusion following stent implantation
Authors: Wu Xueliang , Wang Zhao , Li Tian
Published: October 2020

Rationale:

Recent research shows that in-stent restenosis (ISR) occurs in half of the patients treated with stenting of femoral and popliteal artery for lower extremity arteriosclerotic occlusive disease (LEASO). Combined therapy is mainly used clinically to obtain better medium- and long-term treatment outcomes and reduce the occurrences of reintervention, among which, the combination of excimer laser ablation (ELA) and drug eluting balloon (DEB) is a new and effective choice.

Patient concerns:

A 76-year-old male patient with ISR of right superficial femoral artery after stent implantation was reported.

Diagnosis:

Rechecking angiography indicated severe occlusion of the right superficial femoral artery. The physical examination showed that bilateral femoral and popliteal arteries were accessible whereas right dorsalis and posterior tibial arteries are unaccessible. Ankleolus brachial index (ABI) was 0.92 for left and 0.58 for right.

Interventions:

We performed the operation with ELA and drug balloon DEB on the right superficial femoral artery under local anesthesia and treated with oral antiplatelet drugs after operation.

Outcomes:

The combination treatment was very successful, and postoperative lower extremity arteriogram showed the blood flow was fluent and fast. No recurrence was discovered 3 months after the operation and he had no obvious symptom of claudication.

Lessons:

The combination of ELA and DEB is useful and effective for ISR of peripheral vessel after stent implantation, and this surgical method is worthwhile but need further clinical research for safety confirmation.
Eight rare urinary disorders in a patient with Kallmann syndrome
Authors: Tian Huining , Yan Zi , Lv You , Sun Lin , Gang Xiaokun , Wang Guixia
Published: October 2020

Rationale:

Kallmann syndrome (KS) is a rare inherited genetic disorder characterized by hypogonadotropic hypogonadism and hyposmia/anosmia. Early diagnosis is the key to timely treatment and improvement of prognosis in patients with KS. As the most common complication of KS, renal agenesis can provide clues to early diagnosis and treatment for KS. In this article, we report a case of KS with 8 rare urinary disorders for the first time.

Patient concerns:

A 19-year-old Chinese man presented with 8 rare urinary disorders and a history of bilateral cryptorchidism came to us for micropenis, hyposmia, and delayed puberty.

Diagnosis:

The patient presented with hyposmia, low levels of sex hormones and showed a weak response to the GnRH stimulation test leading to a diagnosis of KS. Two missense mutations were found in further whole-exome sequencing: 1) Kallmann syndrome 1 (KAL1) gene in exon11, c.1600G > A, p. Val534Ile; 2) Prokineticin receptor 2 (PROKR2) gene in exon 2, c.533G > A, p. Trp178Ser. which led to a diagnosis of KS.

Interventions:

The patient underwent replacement therapy of human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG). The patient had previously undergone six surgeries for cryptorchidism and urinary disorders.

Outcomes:

The patient's puberty retardation was effectively alleviated. His serum testosterone (T) reached a normal level (8.280 nmol/mL). During the follow-up period, he presented with Tanner stage II pubic hair development.

Conclusion:

In this article, we report 8 rare urinary disorders with missense mutations of KAL1 and PROKR2 in a case of KS. Among them, bilateral giant kidneys, urinary extravasation of right renal, bilateral megalo-ureters, left ureteral terminal obstruction, bilateral renal cyst and bladder emptying disorder are reported for the first time, which enrich the integrity of urinary disorder types and provide clues to genetic counseling in patients with KS.
Central diabetes insipidus unveiled by glucocorticoid therapy in a patient with an empty sella
Authors: Yang Lei-Yi , Lin Sang , Xie Qi-Bing , Yin Geng
Published: October 2020

Rationale:

Some diseases contribute to hypopituitarism without clinical manifestations and the glucocorticoid therapy may unveil central diabetes insipidus. The condition is rare and usually causes problems for clinical physicians.

Patient concerns:

A 59-year-old woman presented to our hospital due to facial numbness and persistent eyelid heaviness.

Diagnosis:

Physical examination and cerebrospinal fluid examination supported a diagnosis of Guillain–Barré syndrome. Magnetic resonance imaging showed an empty sella. Hormone test indicated hypopituitarism.

Interventions:

The patient received intravenous immunoglobulin and glucocorticoid. Central diabetes insipidus appeared after 20 days. Subsequently, the patient was prescribed 1-desamino-8-D-arginine vasopressin and prednisone.

Outcomes:

During 6 months’ follow-up, the patient's urine output was gradually reduced to normal level.

Lessons:

This case indicated that hypopituitarism may be caused by an empty sella and be masked by adrenal insufficiency. Central diabetes insipidus may present after glucocorticoid therapy.
Acute encephalopathy with biphasic seizures and late reduced diffusion
Authors: Ma Yan-li , Xu Kai-li , Chen Guo-hong , Wang Li , Wang Yuan , Jin Zhi-peng
Published: October 2020

Rationale:

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has been reported almost exclusively in the Japanese population.

Patient concerns:

A 17-month-old male patient presented with fever and seizures, and subsequently fell into a coma. On the second day, he recovered consciousness. On the fourth day, he developed complex partial seizures and fell into a coma again. On day 10, the fever and seizures subsided. Head computed tomography on the first day showed no abnormalities. Brain diffusion-weighted images on the fourth day revealed reduced diffusion in the bilateral subcortical white matter.

Diagnosis:

A diagnosis of AESD was made.

Interventions:

The patient was treated with corticosteroids and intravenous immunoglobulin.

Outcomes:

At the 4-month follow-up, the patient was able to walk independently, and the epileptic seizures were well controlled.

Lessons:

AESD is a rare entity, and treatment with corticosteroids and intravenous immunoglobulin can lead to a favorable prognosis. Clinicians should be aware of this condition, and clinicoradiological features can suggest the diagnosis.
Clinical impact of echocardiography-defined pulmonary hypertension on the clinical outcome in patients with multiple myeloma
Authors: Bae SungA , Kim Kye Hun , Yoon Hyun Ju , Kim Hyung Yoon , Park Hyukjin , Cho Jae Yeong , Kim Min Chul , Kim Yongcheol , Hong Young Joon , Park Hyung Wook , Kim Ju Han , Ahn Youngkeun , Jeong Myung Ho , Cho Jeong Gwan , Park Jong Chun
Published: October 2020

Pulmonary hypertension (PH) is a complication of multiple myeloma (MM); however, the clinical outcomes and prognosis are relatively not well known. We aimed to investigate the risk factors of transthoracic echocardiography-defined PH and its impact on the clinical outcome in patients with MM.

A retrospective study was performed using data from the Chonnam National University Hwasun Hospital database for patients who underwent transthoracic echocardiography (TTE) within 1 month of the MM diagnosis between January 2007 and December 2017. PH was defined as an estimated right ventricular systolic pressure (RVSP) > 40 mmHg. A total of 390 patients were included. TTE-defined PH was observed in 107 patients (27%). During the follow-up period (median, 688 days), all-cause death was noted for 134 patients (34.4%). In the Kaplan-Meier survival analysis, the cumulative overall survival and cardiovascular death-free survival rates were significantly lower in the PH group than in the non-PH group (P < .001). In the propensity score-matched population, RVSP > 40 mmHg on TTE and history of congestive heart failure (CHF) were identified as the significant independent predictors of all-cause and cardiovascular death.

This study reports that the prevalence of TTE-defined PH is higher in patients with MM than in the general population. Moreover, TTE-defined PH and a history of CHF are the independent prognostic factors for all-cause and cardiovascular death in patients with MM. These results highlight the risk of associated cardiovascular disease in patients with MM and emphasize the importance of management strategies that prevent the deterioration of cardiac function.
Characterization of a COPD-Associated NPNT Functional Splicing Genetic Variant in Human Lung Tissue via Long-Read Sequencing
Authors: Saferali Aabida , Xu Zhonghui , Sheynkman Gloria M. , Hersh Craig P. , Cho Michael H. , Silverman Edwin K. , Laederach Alain , Vollmers Christopher , Castaldi Peter J.
Published: October 2020

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Genome-wide association studies (GWAS) have identified over 80 loci that are associated with COPD and emphysema, however for most of these loci the causal variant and gene are unknown. Here, we utilize lung splice quantitative trait loci (sQTL) data from the Genotype-Tissue Expression project (GTEx) and short read sequencing data from the Lung Tissue Research Consortium (LTRC) to characterize a locus in nephronectin (NPNT) associated with COPD case-control status and lung function. We found that the rs34712979 variant is associated with alternative splice junction use in NPNT, specifically for the junction connecting the 2nd and 4th exons (chr4:105898001-105927336) (p=4.02×10−38). This association colocalized with GWAS data for COPD and lung spirometry measures with a posterior probability of 94%, indicating that the same causal genetic variants in NPNT underlie the associations with COPD risk, spirometric measures of lung function, and splicing. Investigation of NPNT short read sequencing revealed that rs34712979 creates a cryptic splice acceptor site which results in the inclusion of a 3 nucleotide exon extension, coding for a serine residue near the N-terminus of the protein. Using Oxford Nanopore Technologies (ONT) long read sequencing we identified 13 NPNT isoforms, 6 of which are predicted to be protein coding. Two of these are full length isoforms which differ only in the 3 nucleotide exon extension whose occurrence differs by genotype. Overall, our data indicate that rs34712979 modulates COPD risk and lung function by creating a novel splice acceptor which results in the inclusion of a 3 nucelotide sequence coding for a serine in the nephronectin protein sequence. Our findings implicate NPNT splicing in contributing to COPD risk, and identify a novel serine insertion in the nephronectin protein that warrants further study.
Analytical evaluation and critical appraisal of early commercial SARS-CoV-2 immunoassays for routine use in a diagnostic laboratory
Authors: Cramer Amanda , Goodman Nigel , Cross Timothy , Gant Vanya , Dziadzio Magdalena
Published: October 2020

BACKGROUND

The objective of this study was to evaluate the performance characteristics of early commercial SARS-CoV-2 antibody assays in mild and asymptomatic subjects to enable the selection of suitable serological assays for routine diagnostic use within HCA Healthcare UK.

METHODS

We used serum samples from a pre-Covid era patient cohort (n=50, pre-December 2019), designated SARS-CoV-2 negative, and serum samples from a SARS-CoV-2 RT-PCR-positive cohort (n=90) taken > 14 days post symptom onset (April-May 2020). We evaluated 6 ELISA assays including one confirmation assay to investigate antibody specificity. We also evaluated one point-of-care lateral flow device and one high throughput electrochemiluminescence immunoassay.

RESULTS

The ELISA specificities ranged from 84-100%, with sensitivities ranging from 75.3-90.0%. The LFIA showed 100% specificity and 80% sensitivity using smaller sample numbers. The Roche CLIA immunoassay showed 100% specificity and 90.7% sensitivity. When used in conjunction, the Euroimmun nucleocapsid (NC) and spike-1 (S1) IgG ELISA assays had a sensitivity of 95.6%. The confirmation IgG assay showed 92.6% of samples tested contained both NC and S1 antibodies, 32.7% had NC, S1 and S2 and 0% had either S1 or S2 only.

CONCLUSIONS

These first generation assays were not calibrated against reference material and the results are reported qualitatively. The Roche assay and the Euroimmun NC and S1 assays had the best sensitivity overall in our hands. Combining the assays detecting NC and S1/S2 antibody increased diagnostic yield. A portfolio of next generation SARS-CoV-2 immunoassays will be necessary in any future studies of herd and vaccine induced immunity.
The Abelson tyrosine kinase and the Nedd4-family ubiquitin ligase Suppressor of Deltex converge at the Notch PPxY motif to regulate endosomal trafficking and signaling
Authors: Sanchez-Luege Nicelio , Miranda-Alban Julio , Sun Xiao , Valbuena Fernando M. , Glick Benjamin S. , Rebay Ilaria
Published: October 2020

The conserved Notch signaling pathway coordinates diverse cellular processes during animal development. Unlike most cell surface receptors that use a cytoplasmic cascade to amplify and diversify signaling dynamics, Notch itself transduces external cues directly to the nucleus. How appropriate signaling dynamics and transcriptional responses are achieved with this pathway architecture remains unclear. Here, we report that the cytoplasmic tyrosine kinase Abelson (Abl) fine-tunes Notch signaling by regulating Notch endocytic trafficking. We show that Abl can directly phosphorylate a PPxY motif important for Nedd4-family ubiquitin-ligase-mediated transfer of Notch into degradative endosomal compartments. Consistent with this, loss of Abl or inhibition of its kinase activity results in aberrant endosomal accumulation of Notch, while mutation of the PPxY tyrosine renders Notch insensitive to such regulation. Phenotypic and genetic interaction studies in the wing, together with parallel assays in cultured cells, show that loss or gain of Abl activity can respectively increase or decrease Notch output. We propose that the Notch PPxY motif operates as a molecular hub that integrates multiple post-translational modifications to regulate Notch trafficking and fine-tune signaling output.
Health Complexity Assessment in Primary Care: a validity and feasibility study of the INTERMED tool
Authors: de Oliveira Camila Almeida , Weber Bernardete , dos Santos Jair Lício Ferreira , Zucoloto Miriane Lucindo , de Camargo Lisa Laredo , Zanetti Ana Carolina Guidorizzi , Rzewuska Magdalena , de Azevedo-Marques João Mazzoncini
Published: October 2020

Background

While considerable attention has been devoted to patients’ health complexity epidemiology, comparatively less attention has been paid to tools to identify and describe, in a personalized and comprehensive way, “complex patients” in primary health care (PHC).

Objective

To evaluate INTERMED tool’s validity and feasibility to assess health complexity in PHC.

Design

Cross-sectional psychometric study.

Setting

Three Brazilian PHC Units.

Participants

230 patients above 18 years of both sexes.

Measurements

Spearman’s rho assessed concurrent validity between the whole INTERMED and their four domains (biological, psychological, social, health system) with other well-validated instruments. Pearson’s X2 measured associations of the sum of INTERMED “current state” items with use of PHC, other health services and medications. Cronbach’s Alpha assessed internal consistency. INTERMED acceptability was measured through patients’ views on questions and answers’ understanding and application length as well as objective application length. Applicability was measured through patients’ views on its relevance to describe health aspects essential to care and INTERMED’s items-related information already existing in patients’ health records.

Results

18.3% of the patients were “complex” (INTERMED’s 20/21 cut-off). Spearman’s correlations located between 0.44 - 0.65. Pearson’s coefficients found were X2 = 26.812 and X2 = 26.883 (both p = 0.020) and X2 = 28.270 (p = 0.013). Cronbach’s Alpha was 0.802. All patients’ views were very favorable. Median application time was 7 minutes and 90% of the INTERMED’s interviews took up to 14 minutes. Only the biological domain had all its items described in more than 50% of the health records.

Limitations

We utilized the cutoff point used in all previous studies, found in research performed in specialized health services.

Conclusion

We found good feasibility (acceptability and applicability), and validity measures comparable to those found from specialized health services. Further investigations of INTERMED predictive validity and suitability for routine PHC use are worthwhile.