bluuebunny/crossref_metadata_2025 huggingface dataset:
Meningoencephalitis in relapsing polychondritis
Authors: Matsumoto Haruki , Tokimura Ryo , Fujita Yuya , Matsuoka Naoki , Asano Tomoyuki , Sato Shuzo , Temmoku Jumpei , Yashiro-Furuya Makiko , Yoshida Kenji , Takahashi Ryoma , Tanaka Shoko , Itagaki Yuya , Honma Mari , Matsuda Nozomu , Watanabe Hiroshi , Migita Kiyoshi , Kanai Kazuaki
Published: June 2021

Rationale:

Aseptic meningoencephalitis is a rare central nervous system complication of relapsing polychondritis (RP).

Patient:

We report a 61-year-old Japanese male patient with spiking fever and impaired consciousness. Neurological examination revealed meningealirritation, and cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis with elevated protein (199 mg/dL) and interleukin-6 (3810 pg/mL). Serological analysis showed high levels of anti-type II collagen antibodies, and the result of auricular biopsy was consistent with the diagnosis of RP showing cartilage degeneration surrounded by inflammatory cell infiltrations.

Diagnosis:

A clinical diagnosis of RP was made according to the diagnostic criteria established by MacAdams et al.

Intervention:

Steroid pulse therapy (methylprednisolone 1000 mg, consecutive 3 days) followed by oral prednisolone (60 mg/day) resolved the patient's high fever and disturbance of consciousness.

Outcomes:

The patient rapidly improved after steroid treatments and has a normal quality of life under the maintenance dose of steroid plus methotrexate (4 mg/week).

Lessons:

RP-associated meningoencephalitis is a rare complication with significant morbidity and mortality. It should be considered and differentiated in patients with RP with unexplained spiking fever and impaired consciousness. In addition, the assessment of cerebrospinal fluid interleukin-6 levels may be useful to investigate the disease activity of RP-related meningoencephalitis. Further prospective studies are required to confirm this result.
Mycobacterium avium complex peritonitis in a pediatric patient on peritoneal dialysis
Authors: Yokota Shunsuke , Nishi Kentaro , Ishiwa Sho , Uda Kazuhiro , Shoji Kensuke , Kamei Koichi
Published: June 2021

Introduction:

Peritonitis due to Mycobacterium avium complex (MAC) is a rare but life-threatening complication in patients on peritoneal dialysis (PD). However, optimal therapeutic regimen, treatment duration, and appropriate timing of kidney transplantation (KT) after treatment are unknown.

Symptoms:

We herein report a 4-year-old boy on PD due to end-stage kidney disease resulting from bilateral hypoplastic kidneys. He was admitted for peritonitis complaining fever, abdominal pain, and cloudy peritoneal effluent on PD after accidentally biting and opening the PD catheter while in the bath. Initial treatment with vancomycin and ceftazidime for 2 weeks was successful, although peritonitis recurred 37 days after discharge.

Diagnosis:

Mycobacterial culture was positive 9 days after readmission, and MAC was grown in the PD culture on day 30. We diagnosed him with MAC peritonitis that occurred on PD.

Interventions:

Clarithromycin, ethambutol, and rifampicin were initiated. The PD catheter was removed, and hemodialysis was initiated with a cuffed catheter inserted in the internal jugular vein. Follow-up observation for 8 months after the cessation of 1-year anti-mycobacterial therapy confirmed no recurrence of MAC infection, and the patient received living-donor KT from his father.

Outcomes:

His renal function was stable, with no recurrence of MAC peritonitis at 2 years after the KT.

Conclusion:

To the best of our knowledge, this is the first report of a patient who successfully underwent KT after receiving treatment for MAC peritonitis. One-year anti-mycobacterial therapy, PD catheter removal, 8-month observation after the cessation of therapy led the successful KT, although further investigation is warranted to confirm the efficacy of this approach.
High-fidelity simulation is associated with good discriminability in emergency medicine residents’ in-training examinations
Authors: Chen Shou-Yen , Chaou Chung-Hsien , Yu Shiuan-Ruey , Chang Yu-Che , Ng Chip-Jin , Liu Pin
Published: June 2021

In-training examinations (ITEs), arranged during residency training, evaluate the residents’ performances periodically. There is limited literature focusing on the effectiveness of resident ITEs in the format of simulation-based examinations, as compared to traditional oral or written tests. Our primary objective is to investigate the effectiveness and discriminative ability of high-fidelity simulation compared with other measurement formats in emergency medicine (EM) residency training program.

This is a retrospective cohort study. During the 5-year study period, 8 ITEs were administered to 68 EM residents, and 253 ITE measurements were collected. Different ITE scores were calculated and presented as mean and standard deviation. The ITEs were categorized into written, oral, or high-fidelity simulation test forms. Discrimination of ITE scores between different training years of residency was examined using a one-way analysis of variance test.

The high-fidelity simulation scores correlated to the progression of EM training, and residents in their fourth training year (R4) had the highest scores consistently, followed by R3, R2, and then R1. The oral test scores had similar results but not as consistent as the high-fidelity simulation tests. The written test scores distribution failed to discriminate the residents’ seniority. The high-fidelity simulation test had the best discriminative ability and better correlation between different EM residency training years comparing to other forms.

High-fidelity simulation tests had the good discriminative ability and were well correlated to the EM training year. We suggest high-fidelity simulation should be a part of ITE in training programs associated with critical or emergency patient cares.
Clinical assessment of prophylactic chemotherapy in treating with hydatidiform mole
Authors: Xu Feng , Zheng Yan-Li , Lu Xiao-Yan , Qiao Hai-Feng , Wang Ying
Published: June 2021

Background:

Hydatidiform mole (HM) is more common as molar pregnancy. It is a disease classified under the category of gestational trophoblastic diseases, which could metastasize after originating in the placenta. A majority of females suffering from molar pregnancies are curable by evacuating retained products of conception and the patient's fertility is preserved. In some cases, the growth perseveres and leads to gestational trophoblastic neoplasia, which is an extremely malicious condition that needs chemo-based treatment. There is a possibility to lessen the risk of gestational trophoblastic disease in females with HM through the administration of prophylactic chemo. Yet, there is controversy regarding prophylactic chemotherapy administered pre-or-post removal of HM to curtail the malignant sequelae. Therefore, we will conduct this research to assess both the efficacy as well as security of using prophylactic chemotherapy to treat HM.

Methods:

In the preliminary review, the authors will search for randomized controlled trials involving prophylactic chemotherapy to treat HM. The literature search is carried out in the following electronic databases from their inception to May 2021: Chinese National Knowledge Infrastructure, Chinese BioMedical Literature, and WanFang database are the three Chinese language databases. Web of Science, PubMed, Cochrane Library, and EMBASE are the four English language databases. The authors will also perform a manual search through the bibliographies in related literature to find extra articles and ongoing studies. Two independent authors will assess the literature according to an inclusion criteria, use a specialized data collection table to extract data, and use the Cochrane ‘Risk of bias’ tool for evaluating any possible bias risk in the selected articles. Data synthesis and statistical operations are completed with the RevMan software (v. 5.3).

Results:

The present systematic analysis provides a rationalized synthesis of existing evidence related to the use of prophylactic chemotherapy in the treatment of HM.

Conclusion:

Our findings will summarize the current evidences for prophylactic chemotherapy in the treatment of HM.

Ethics and dissemination:

An ethics approval is nonrequired because pre published results will be used.

Registration number:

DOI 10.17605/OSF.IO/6QV52 (https://osf.io/6qv52/)
Alpha lipoic acid with pulsed radiofrequency in treatment of chronic lumbosacral radicular pain
Authors: Abdelrahman Khaled A. , Ibrahim Abdelrady S. , Osman Ayman M. , Aly Mohamed G. , Ali Abdelhady S. , Farrag Waleed S.
Published: June 2021

Background:

The effect of adding alpha lipoic acid (ALA) to pulsed radiofrequency (PRF) for treatment of lumbar-sacral pain was evaluated.

Objective:

to evaluate the effect of using ALA as an adjuvant therapy with PRF for treatment of chronic lumbosacral radicular pain caused by herniated disc.

Methods:

One hundred twenty patients with lumbo-sacral radicular pain allocated into 2 groups. Group I: treated with PRF at 42°C for 120 seconds. Group II: treated as in group I, plus oral ALA 600 mg (Thiotacid 600 mg, EVA PHARMA, Egypt) three times per day (1800 mg/day) for 3 weeks then 600 mg once daily for 2 weeks. The lumbo-sacral radicular pain evaluated using the numerical rating pain score and Oswestry Disability Index.

Results:

Success rate was significantly higher in group II at 3 and 6 months after intervention. The median values of the numerical rating pain score and the Oswestry Disability Index were significantly lower in group II with no significant difference in Epworth Sleepiness Scale. No major complications were reported in both groups.

Conclusion:

The current study supports the use of ALA with PRF on the dorsal root ganglion for treating lumbosacral radicular pain.
Flow-diverting device versus coil embolization for unruptured intracranial aneurysm
Authors: Xia Jia-Lin , Li Guang-Lei , Liu Hong-En , Feng-Fei Xia , Gu Xin-Dong
Published: June 2021

Background:

Both coil embolization (CE) and flow-diverting device (FDD) placement are widely used for treatment of intracranial aneurysms (IAs). The aim of this meta-analysis is to compare the relative clinical safety and efficacy of FDD and CE for the treatment of unruptured IAs.

Methods:

The PubMed, Embase, and Cochrane Library databases were searched for relevant studies from the date of inception through April 2020. The primary endpoint for this meta-analysis was the 6-month rate of complete occlusion, while secondary endpoints included rates of retreatment, complications, and parental arterial patency.

Results:

This meta-analysis includes 8 studies, which included 839 total patients that underwent FDD and 2734 that underwent CE. FDD group exhibited a significantly higher pooled 6-month complete occlusion rate (P = .02). The subgroup analysis demonstrated that FDD treatment was associated with significantly higher pooled 6-month complete occlusion rates in patients with large or giant IAs (P < .00001), whereas no differences in 6-month complete occlusion rates were observed between the FDD and CE groups of patients with non-large/giant IAs (P = .83). The pooled retreatment (P = .16) and complication (P = .15) rates were comparable between 2 groups. The CE group exhibited significantly higher pooled parent artery patency rate (P = .01). The funnel plots did not reveal any evidence of publication bias.

Conclusions:

FDDs can be used to effectively and safely treat large and giant IAs, achieving higher rates of complete occlusion than CE treatment. For non-large/giant IAs, we observed comparable efficacy between FDD and CE treatments.
Atezolizumab and bevacizumab-induced encephalitis in advanced hepatocellular carcinoma
Authors: Özdirik Burcin , Jost-Brinkmann Fabian , Savic Lynn Jeanette , Mohr Raphael , Tacke Frank , Ploner Christoph J. , Roderburg Christoph , Müller Tobias
Published: June 2021

Introduction:

On the basis of the results of the IMBRAVE-150 trial, the combination of atezolizumab, a programmed cell death ligand 1 (PD-L1) antibody, as well as bevacizumab, a vascular endothelial growth factor (VEGF) antibody, represents a promising novel first-line therapy in patients with advanced hepatocellular carcinoma (HCC). Despite favorable safety data, serious adverse events have been described. However, central nervous system complications such as encephalitis have rarely been reported. We present the case of a 70-year-old woman with hepatitis C virus (HCV)-related liver cirrhosis and advanced HCC who developed severe encephalitis after only one cycle of atezolizumab/bevacizumab.

Patient concerns:

Ten days after administration, the patient presented with confusion, somnolence, and emesis. Within a few days, the patient's condition deteriorated, and mechanical ventilation became necessary.

Diagnosis:

Cerebrospinal fluid (CSF) analysis showed increased cell count and elevated protein values. Further work-up revealed no signs of an infectious, paraneoplastic, or other autoimmune cause.

Intervention:

Suspecting an atezolizumab/bevacizumab-related encephalitis, we initiated a high-dose steroid pulse therapy as well as repeated plasmapheresis, which resulted in clinical improvement and remission of CSF abnormalities.

Outcome:

Despite successful weaning and transfer to a rehabilitation ward, the patient died of progressive liver cancer 76 days after initial treatment with atezolizumab/bevacizumab, showing no response.

Conclusion:

This case illustrates that rapid immunosuppressive treatment with prednisolone can result in remission even of severe encephalitis. We discuss this case in the context of available literature and previously reported cases of atezolizumab-induced encephalitis in different tumor entities, highlighting the diagnostic challenges in oncologic patients treated with immune checkpoint-inhibitors.
The use of cisplatin in patients after kidney transplantation with chronic renal insufficiency
Authors: Pokrivcak Tomas , Lakomy Radek , Kazda Tomas , Poprach Alexandr , Fabian Pavel , Kiss Igor
Published: June 2021

Rationale:

The use of cisplatin in patients with chronic kidney disease (CKD) is risky and depends on a number of factors. The optimal procedure in stage I of a non seminomatous germ cell tumor without proven lymphangioinvasion after orchiectomy is controversial and is the subject of a number of discussions due to the lack of randomized studies assessing individual treatment options. The adjuvant method of choice is surveillance or application of cisplatin-based chemotherapy with the risk of treatment related nephrotoxicity. Information about cisplatin safety in renal transplant patients is particularly limited. The aim of this paper is to share the experience with the application of adjuvant chemotherapy Bleomycin, Etoposide, Cisplatin (BEP) in high-risk patient with nonseminoma after kidney transplantation.

Patient concerns:

We report a case report of rare group of high-risk patient with non-seminomatous germ cell testicular tumor (NSGCT) after kidney transplantation before application of adjuvant chemotherapy BEP. Patient presented with month-long discomfort in the scrotal area. Previously, he was treated with chronic kidney disease based on chronic glomerulonephritis, which was treated with repeated kidney transplantation.

Diagnosis:

The ultrasound examination for a month-long discomfort in the scrotal area found a solid mass of the left testis. Radical inguinal orchiectomy confirmed NSGCT with the presence of lymphovascular invasion (LVI). Postoperative staging with computed tomography of the chest and abdomen did not show obvious dissemination of the disease.

Interventions:

Reducing original dose of chemotherapeutics according to the recommendations of the summary of product characteristics led to only a transient increase in creatinine levels.

Outcomes:

The 5-year risk of relapse in surveillance was reduced to around 3% by applying cisplatin-based chemotherapy.

Lessons:

Application of cisplatin-based chemotherapy is safe and effective in patients with CKD and in patients with a kidney transplant.
Total uterine prolapse complicated with vesicovaginal fistula
Authors: Ting Ning-Shiuan , Lee Hsiang-Chen , Ke Jia-Ying , Li Pei-Chen , Ding Dah-Ching
Published: June 2021

Rationale:

Vesicovaginal fistula (VVF) most commonly occurs due to iatrogenic injury during surgery or obstructed labor. We report a rare case of a patient with severe pelvic organ prolapse who developed VVF even though pessary had not been used.

Patient concerns:

A 63-year-old postmenopausal woman, para 3 (all spontaneous vaginal deliveries), complained of vaginal bulging sensation and involuntary urinary leakage for 3 years.

Diagnosis:

Stage IV uterine prolapse with VVF.

Interventions:

She underwent transvaginal VVF repair combined with total vaginal hysterectomy and sacrospinous ligament fixation. The postoperative course was uncomplicated.

Outcomes:

The patient remained free of complications during the 1-year follow-up.

Lessons:

This case illustrates the point that patients with pelvic organ prolapse (POP) should be treated promptly and careful follow-up should be conducted. Clinicians should be aware of the symptoms of VVF to ensure its early diagnosis and treatment.
The effectiveness of acupoint application of traditional Chinese medicine in treating primary dysmenorrhea
Authors: Liu Yanze , Yao Lin , Yan Bing , Jiang Hailin , Zhao Jinying , Cao Jiazhen , Li Mengyuan , Liu Xiaona , Ha Lijuan , Tie Li , Liu Chengyu , Wang Fuchun
Published: June 2021

Background:

Primary dysmenorrhea (PD) is a functional disease of the female reproductive system, which has adverse effects on patients’ physical and mental health and quality of life. At present, acupoint application of traditional Chinese medicine (TCM) as adjuvant therapy is undergoing clinical trials in different medical centers. However, there is no systematic review or meta-analysis to evaluate the efficacy of acupoint application of TCM in the treatment of PD. There is also a lack of systematic evaluation and analysis of acupoints and herbs.

Methods:

All randomized controlled trials related to acupoint catgut embedding therapy on PD will be searched in the following electronic databases: Cochrane Central Registry of controlled trials, PubMed, Wed of Science, EMBASE, Science Net, China Biomedical Literature Database, China Science Journal Database, China National Knowledge Infrastructure and Wan-Fang Database, from inception to May, 2021 were searched without language restrictions. The primary outcomes contain visual analog score, The Cox Menstrual Symptom Scale, while the secondary outcomes consist of adverse events and the recurrence rate. Two reviewers will independently perform data selection, data synthesis, and quality assessment. Data meeting the inclusion criteria will be extracted and analyzed by Revman v.5.3 software. Two reviewers will evaluate the study using the Cochrane collaborative bias risk tool. We will use the scoring method to assess the overall quality of the evidence supporting the main results. We will also use Spass software (version 19.0) for complex network analysis to explore the potential core prescription of acupoint application of traditional Chinese medicine in the treatment of PD.

Results:

This study will analyze the clinical effective rate, functional outcomes, quality of life, improvement of clinical symptoms of PD, and effective prescriptions of acupoint application for patients with PD.

Conclusion:

Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint application for patients with PD.

PROSPERO registration number: CRD 42021244357
Clinical outcomes and healthcare utilization of acute hepatitis A virus infection with acute kidney injury in hospitalized patients
Authors: Khan Ahmad , Sami Khadija , Malik Adnan , Mujtaba Bhinder Muhammad , Naseem Khadija , Gupta Kamesh , Siddiqui Arsalan , Mansoor Emad , Singh Shailendra , Mumtaz Khalid
Published: June 2021

Background

Patients with acute hepatitis A virus (HAV) infection are at risk of developing acute kidney injury (AKI) which may result in increased healthcare resource utilization and worse clinical outcomes. We investigated the impact of AKI on healthcare utilization and clinical outcomes in patients hospitalized with acute HAV infection utilizing a large database.

Methods

We queried the National Inpatient Sample (NIS) 2007–2014 to identify acute HAV infection-related hospitalizations with and without AKI. Primary outcomes were prevalence of AKI and its predictors with secondary outcomes included the mean length of stay (LOS), hospitalization cost and mortality in both groups.

Results

Out of 68 364 acute HAV infection-related hospitalizations, 47 620 met our study criteria and 7458 (15.7%) had concurrent AKI. HAV patients with AKI were older (62.5 vs. 53.7 years; P value <0.001). A higher mean LOS (10.03 vs. 5.6 days; P value <0.001) and mean total hospitalization cost ($27 171.35 vs. $12 790.26; P value <0.001) were observed in HAV patients with the AKI group. A total of 1032 patients (13.8%) in the AKI group died during the same hospitalization as compared to 681 patients (1.5%) in the non-AKI group, P value <0.001. AKI in HAV was also found to be an independent predictor of mortality [adjusted odds ratio (aOR), 3.28; 95% confidence interval, 2.23–4.84; P value <0.001) after adjusting for the confounding factors.

Conclusion

We found that 15.67% of patients hospitalized with acute HAV had AKI which contributed to increased healthcare utilization and higher mortality which is preventable.
Nonalcoholic fatty liver disease is associated with a higher incidence of coeliac disease
Authors: Roderburg Christoph , Loosen Sven , Kostev Karel , Demir Münevver , Joerdens Markus S , Luedde Tom
Published: June 2021

Background

Recently the incidence of nonalcoholic fatty liver disease (NAFLD) has risen to become the most frequent liver disease worldwide. NAFLD is not a disease limited to the liver, but rather represents a systemic inflammatory disease involving multiple organ systems. Previous studies have suggested an association between NAFLD and coeliac disease, another disease related to inflammation. As the available clinical data is scarce and at least partially contradictory, we aimed at investigating a potential association between NAFLD and celiac disease in outpatients in Germany.

Methods

Using the Disease Analyzer database featuring data on diagnoses, prescriptions and demographic variables for 7.49 million cases of patients followed in general practices in Germany, we matched a total of 57 336 patients with NAFLD/diagnosed between 2000 and 2015 to a cohort of equal size without NAFLD by age, sex and index year. Incidence of celiac disease was compared between groups within 10 years from the index date.

Results

During the 10-years observation period, we observed a higher incidence of coeliac disease in NAFLD patients compared to patients without NAFLD (11.2 vs. 7.5 cases per 100 000 patients’ years). Interestingly, this association was most prominent in men (hazard ratio, 2.02; 95% CI, 1.01–4.04) and patients between 18 and 50 years (hazard ratio, 2.79; 95% CI, 1.12–6.94).

Our data suggest that NAFLD promotes the development of coeliac disease particularly in young men. This finding argues that coeliac disease should be recognized as another nonliver-related complication of NAFLD and suggests screening of selected NAFLD patients for the presence of coeliac disease.
Toward improving the specificity of perturbation-based training through assessment of dynamic balancing responses: a series of N-of-1 studies in subacute stroke
Authors: Zadravec Matjaž , Olenšek Andrej , Rudolf Marko , Bizovičar Nataša , Goljar Nika , Matjačić Zlatko
Published: June 2021

Perturbation-based balance training (PBT) has been shown to improve reactive balancing abilities in chronic stroke. To inform future investigations in the subacute phase of stroke, the objective of this series of N-of-1 studies was to investigate the range of balancing responses to unexpected mechanical perturbations applied to the pelvis during walking on an instrumented treadmill before and after PBT training. Three subacute stroke subjects were assessed on each occasion with clinical tests and biomechanical measurements following perturbations applied in forward, backward, inward and outward directions. After 15 daily sessions of PBT, most clinical mobility outcomes showed improvements in all three subjects. Assessment of reactive balancing also showed improvements in all subjects when responding to perturbations in backward and inward directions whereas the changes following perturbations in forward and outward directions were subject-specific. The results suggest that PBT should be individually tailored to target balance deficiencies identified through a serial biomechanical assessment.
Risk factors and outcomes of HIV-associated stroke in Zambia
Authors: Zimba Stanley , Nutakki Aparna , Chishimba Lorraine , Chomba Mashina , Bahouth Mona , Gottesman Rebecca F. , Saylor Deanna
Published: June 2021

Objective:

To compare risk factors and clinical outcomes between people with HIV (PWH) and HIV-uninfected (HIV−) adults with stroke hospitalized in Zambia.

Methods:

We retrospectively reviewed charts of all adults admitted to the University Teaching Hospital in Lusaka, Zambia with a clinical diagnosis of stroke between October 2018 and March 2019. Standardized data collection instruments were used to collect demographic, clinical, laboratory and imaging results. Comparison between individuals with and without HIV infection was made using t tests for continuous parametric variables, Wilcoxon rank-sum tests for continuous nonparametric variables, and chi-square analyses for categorical variables.

Results:

Two hundred and seventy-two adults with stroke were admitted of whom 58 (21%) were PWH. Compared with HIV− participants, PWH were younger [(48 ± 14) years versus 62 ± 18) years, P < 0.001]. PWH were less likely to have hypertension (65 versus 83%, P = 0.003) and more likely to have no traditional cerebrovascular risk factors (34 versus 15%, P = 0.01). Deep vein thrombosis (DVT) (4 versus 1%, P = 0.04) was more common during hospitalization amongst PWH but there was no difference in in-hospital mortality (21 versus 23%, P = 0.65). Among PWH with stroke, factors associated with in-hospital mortality were Glasgow Coma Scale (GCS) on admission (7 versus 10, P = 0.046), hypertension (92 versus 59%, P = 0.04) and fever (58 versus 13%, P = 0.003).

Conclusion:

This Zambian cohort of PWH and stroke is notable for being significantly younger with fewer traditional stroke risk factors but higher rates of DVT than their HIV-uninfected counterparts. GCS on admission, hypertension and fever were associated with in-hospital mortality.
Does Syphilis Increase the Risk of HIV-RNA Elevation >200 Copies/mL in HIV-Positive Patients Under Effective Antiretroviral Treatment? Data From the ICONA Cohort
Authors: Giacomelli Andrea , Cozzi-Lepri Alessandro , Cingolani Antonella , Tavelli Alessandro , Mazzotta Valentina , Tesoro Daniele , Bassetti Matteo , Castagna Antonella , Di Biagio Antonio , Lichter Miriam , Monforte Antonella d'Arminio , Rusconi Stefano ,   on behalf of the ICONA Foundation Study Group
Published: June 2021

Background:

To assess the impact of syphilis infection on the risk of HIV-RNA elevation in people living with HIV (PLWH) with current HIV-RNA ≤50 copies/mL.

Setting:

The Italian Cohort Naive Antiretrovirals.

Methods:

All PLWH (2009–2020) under antiretroviral treatment with at least 2 consecutive HIV-RNA values ≤50 copies/mL before the date of syphilis diagnosis and at least 1 HIV-RNA determination after the syphilis event were enrolled. A control group of PLWH without syphilis was matched for mode of HIV transmission. Outcomes were defined using the first HIV-RNA measure in the time window ranging between −2 and +6 months of the diagnosis/index date. The primary outcome used a single value >200 copies/mL to define HIV-RNA elevation associated with risk of transmission. The association between syphilis infection and the protocol defined outcome was evaluated using logistic regression analysis.

Results:

Nine hundred twenty-six PLWH with a syphilis event were enrolled and matched with a random sample of 1370 PLWH without syphilis. Eighteen of the 926 (1.9%) with syphilis had ≥1 HIV-RNA >200 copies/mL in the window vs. 29/1370 (2.1%) of the not exposed (P = 0.77). In the multivariable analysis adjusted for age, year of diagnosis/index date, and clinical site, syphilis infection was not associated with the risk of HIV-RNA >200 copies/mL (adjusted odds ratio 0.81; 95% confidence interval 0.43–1.52, P = 0.508).

Conclusions:

We did not find any evidence for an association between syphilis infection and viral elevation >200 copies/mL.
Collagen Nanofilm-Coated Partially Deproteinized Bone Combined With Bone Mesenchymal Stem Cells for Rat Femoral Defect Repair by Bone Tissue Engineering
Authors: Liu Jiajie , Jin Liang , Zhou Qingzhu , Huang Wenli , Wang Songmei , Huang Xinwei , Zhao Xian
Published: June 2021

Background

The advantages of good biocompatibility, low degradation and low antigenicity of collagen, and the osteogenic differentiation characteristics of bone mesenchymal stem cells (BMSCs) were used to promote the recovery of bone defects using partially deproteinized bone (PDPB) by bone tissue engineering (BTE).

Methods

The BMSCs were identified by examining their potential for osteogenic, lipogenic, and chondrogenic differentiation. The prepared pure PDPB was ground into bone blocks 4 × 2 × 2 mm in size, which were divided into the following groups: PDPB group, PDPB + collagen group, PDPB + collagen + BMSC group, PDPB with a composite collagen nanofilm, and BMSCs injected into the tail vein. At 2, 4, 6, and 8 weeks after surgery, the effects of the implants in the different groups on bone defect repair were continuously and dynamically observed through x-ray examination, gross specimen observation, histological evaluation, and microvascularization detection.

Results

Postoperative x-ray examination and gross specimen observation revealed that, after 4 to 8 weeks, the external contour of the graft was gradually weakened, and the transverse comparison showed that the absorption of the graft and fusion of the defect were more obvious in PDPB + collagen + BMSC group than in PDPB group and PDPB + collagen group, and the healing was better (P < 0.05). Hematoxylin and eosin staining of histological sections showed very active proliferation of trabecular hematopoietic cells in groups PDPB + collagen + BMSC and PDPB + collagen. Masson's trichrome staining for evaluation of bone defect repair showed that the mean percent area of collagen fibers was greater in PDPB + collagen + BMSC group than in the PDPB group, with degradation of the scaffold material and the completion of repair. Immunofluorescence staining showed significantly enhanced expression of the vascular marker CD31 in group C (P < 0.05).

Conclusions

The proposed hybrid structure of the collagen matrix and PDPB provides an ideal 3-dimensional microenvironment for patient-specific BTE and cell therapy applications. The results showed that collagen appeared to regulate MSC-mediated osteogenesis and increase the migration and invasion of BMSCs. The combination of collagen nanofilm and biological bone transplantation with BMSC transplantation enhanced the proliferation and potential of the BMSCs for bone regeneration, successfully promoting bone repair after implantation at the defect site. This method may provide a new idea for treating clinical bone defects through BTE.
Improving Safety Recommendations Before Implementation: A Simulation-Based Event Analysis to Optimize Interventions Designed to Prevent Recurrence of Adverse Events
Authors: Langevin Mélissa , Ward Natalie , Fitzgibbons Colleen , Ramsay Christa , Hogue Melanie , Lobos Anna-Theresa
Published: June 2021

Introduction

Pediatric inpatients are at high risk of adverse events (AE). Traditionally, root cause analysis was used to analyze AEs and identify recommendations for change. Simulation-based event analysis (SBEA) is a protocol that systematically reviews AEs by recreating them using in situ simulated patients, to understand clinician decision making, improve error discovery, and, through guided sequential debriefing, recommend interventions for error prevention. Studies suggest that these interventions are rarely tested before dissemination. This study investigates the use of simulation to optimize recommendations generated from SBEA before implementation.

Methods

Recommendations and interventions developed through SBEA of 2 hospital-based AEs (event A: error of commission; event B: error of detection) were tested using in situ simulation. Each scenario was repeated 8 times. Interventions were modified based on participant feedback until the error stopped occurring and data saturation was reached.

Results

Data saturation was reached after 6 simulations for both scenarios. For scenario A, a critical error was repeated during the first 2 scenarios using the initial interventions. After modifications, errors were corrected or mitigated in the remaining 6 scenarios. For scenario B, 1 intervention, the nursing checklist, had the highest impact, decreasing average time to error detection to 6 minutes. Based on feedback from participants, changes were made to all but one of the original proposed interventions.

Conclusions

Even interventions developed through improved analysis techniques, like SBEA, require testing and modification. Simulation optimizes interventions and provides opportunity to assess efficacy in real-life settings with clinicians before widespread implementation.
Coadministration of AYUSH 64 as an adjunct to Standard of Care in mild and moderate COVID-19: A randomised, controlled, multicentric clinical trial
Authors: Chopra Arvind , Tillu Girish , Chuadhary Kuldeep , Reddy Govind , Srivastava Alok , Lakdawala Muffazal , Gode Dilip , Reddy Himanshu , Tamboli Sanjay , Saluja Manjit , Sarmukkaddam Sanjeev , Gundeti Manohar , Raut Ashwinikumar , Rao BCS , Yadav Babita , Srikanth Narayanam , Patwardhan Bhushan
Published: June 2021

Objectives

To compare the co-administration of an Ayurvedic drug AYUSH 64 as an adjunct to standard of care (SOC) and SOC for efficacy and safety in the management of COVID-19.

Design

Multicentre, parallel efficacy, randomized, controlled, open label, assessor blind, exploratory trial with a convenience sample. Patients followed to complete 12 weeks of study duration.

Setting

COVID-19 dedicated non-intensive care wards at 1 government hospital, 1 medical college teaching hospital and 1 medical university teaching hospital

Participants

140 consenting, eligible, hospitalized adult patients suffering from mild and moderate symptomatic COVID-19 and confirmed by a diagnostic (SARS-CoV-2) RT-PCR assay on nasal and throat swab were randomized to SOC or SOC plus AYUSH 64. To be withdrawn if disease becomes severe.

Interventions

Two tablets of AYUSH 64, 500 mg each, twice daily after meals, and continued till study completion. SOC (symptomatic and supportive) as per national guidelines of India for mild and moderate disease.

Main outcome measures

Time period to clinical recovery (CR) from randomization baseline and proportion with CR within 28 days time frame; CR defined in the protocol

Results

140 patients randomized (70 in each arm); 138 patients with CR qualified for analysis. Both groups were matched at baseline. The mean time to CR from randomization was significantly superior in AYUSH 64 group (95% CI -3.03 to 0.59 days); a higher proportion (69.7%) in the first week (p=0.046, Chi-square). No significant differences observed for COVID-19 related blood assays (such as D-Dimer). AYUSH 64 arm showed significant (p<0.05) superior persistent improvement in general health, quality of life, fatigue, anxiety, stress, sleep and other psychosocial metrics. 1 patient on SOC required critical care. 48 adverse events (AE) reported in each group. Barring three SAE (in SOC), AE were mild and none were drug related. 22 participants (8 on AYUSH) were withdrawn. No deaths were reported.

Conclusions

AYUSH 64 hastened recovery, reduced hospitalization and improved overall health in mild and moderate COVID-19 when co-administered with SOC under medical supervision. It was safe and well tolerated. Further studies are warranted.

Trial registration

The Clinical Trials Registry India Number CTRI/2020/06/025557

Funding

CCRAS, Ministry of AYUSH, Government of India
Induced ligno-suberin vascular coating and tyramine-derived hydroxycinnamic acid amides restrict Ralstonia solanacearum colonization in resistant tomato roots
Authors: Kashyap Anurag , Capellades Montserrat , Zhang Weiqi , Srinivasan Sumithra , Laromaine Anna , Serra Olga , Figueras Mercè , Rencoret Jorge , Gutiérrez Ana , Valls Marc , Coll Nuria S.
Published: June 2021

The soil borne pathogen Ralstonia solanacearum is the causing agent of bacterial wilt, a devastating disease affecting major agricultural crops. R. solanacearum enters plants through the roots and reaches the vasculature, causing rapid wilting. We recently showed that tomato varieties resistant to bacterial wilt restrict bacterial movement in the plant. In the present work we go a step forward by identifying the physico-chemical nature of the barriers induced in resistant tomato roots in response to R. solanacearum. We describe that resistant tomato specifically responds to infection by assembling de novo a structural barrier at the vasculature formed by a ligno-suberin coating and tyramine-derived hydroxycinnamic acid amides (HCAAs). On the contrary, susceptible tomato does not form these reinforcements in response to the pathogen but instead displays lignin structural changes compatible with its degradation. Further, we show that overexpressing genes of the ligno-suberin pathway in a commercial susceptible variety of tomato restricts R. solanacearum movement inside the plant and slows disease progression, enhancing resistance to the pathogen. We thus propose that the induced barrier in resistant plants does not only restrict the movement of the pathogen, but may also prevent cell wall degradation by the pathogen and confer anti-microbial properties.
Integrated Metabolomics to Reveal the Impacts of Common Antibiotics based on Drug Resistance Prediction of Gut Microbiota
Authors: Gao Pei , Huang Ming , Ono Naoaki , Kanaya Shigehiko , Altaf-Ul-Amin MD
Published: June 2021

Due to the close interaction between the host and the gut microbiota, the alterations in gut microbiota metabolism may therefore contribute to various diseases. How to use antibiotics more wisely in clinical practice is a promising task in the field of pathophysiology related to gut microbiota. The hope fueling this research is that the alteration of gut microbial communities are paralleled by their capacity on metabolomic from the combined perspective of microbiome and metabolomics. In order to reveal the impacts of antibiotics on microbiota-associated host metabolomic phenotypes, a feasible methodology should be well developed to assess the pervasive effects of antibiotics on the population structure of gut microbial communities. Our attempt starts from predicting specific resistance phenotypes of the individuals in isolation from the rest of the gut microbiota community, according to their resistant genotypes. Once resistance phenotypes of microbiome is determined, we integrated metabolomics with machine learning by applying various analysis algorithms to explore the relationship between the predicted resistance and metabolites, including what the microbial community is after medication, which microbes produce metabolites, and how these metabolites enrich.
Through hawks’ eyes: reconstructing a bird’s visual field in flight to study gaze strategy and attention during perching and obstacle avoidance
Authors: Miñano Sofía , Taylor Graham K.
Published: June 2021

We present a method to analyse visual attention of a bird in flight, that combines motion capture data with renderings from virtual cameras. We applied it to a small subset of a larger dataset of perching and obstacle avoidance manoeuvres, and studied visual field stabilisation and gaze shifts. Our approach allows us to synthesise visual cues available to the bird during flight, such as depth information and optic flow, which can lead to novel insights into the bird’s gaze strategy in flight. This preliminary work demonstrates the method and suggests several new hypotheses to investigate with the full dataset.
Oxytocin receptor antagonism during song tutoring in zebra finches reduces preference for and learning of the tutor’s song
Authors: Pilgeram Natalie R. , Baran Nicole M. , Bhise Aditya , Davis Matthew T. , Kim Emily , Lee Sumin , Rodriguez-Saltos Carlos A. , Maney Donna L.
Published: June 2021

In species with vocal learning, acquiring species-typical vocalizations relies on early social orienting. In zebra finches (Taeniopygia guttata), for example, learning song requires dynamic social interactions with a “tutor” during an early sensitive period. The oxytocin system plays a central role in social orienting across species, yet it is unknown whether this system participates in the attentional and motivational processes that support vocal learning. Here, we tested whether blocking oxytocin receptors during exposure to tutors would impact learning from those tutors. Juvenile, song-naïve males were each tutored by two unfamiliar adults. During exposure to one tutor, juveniles were treated with oxytocin receptor antagonist (OTA) and during exposure to the other, saline (control). We found that OTA significantly reduced behaviors associated with approach and attention during tutoring sessions. Next, using an operant assay in which exposure to the two songs was balanced, we found that the juveniles preferred the control song over the OTA song. The developmental trajectory of preference for the control song resembled the pattern shown by father-reared birds choosing to hear their father’s song. Finally, the adult songs of the tutored birds more closely resembled control song than OTA song. The magnitude of this difference was significantly predicted by the early preference for the control song. Overall, oxytocin antagonism during exposure to a tutor seemed to bias juveniles against that tutor and his song. Our results suggest that oxytocin receptors play a role in socially-guided vocal learning in zebra finches, perhaps by affecting attention and motivation during tutoring.
Peripheral CB1 receptor blockade acts as a memory enhancer through an adrenergic-dependent mechanism
Authors: Martínez-Torres Sara , Bergadà-Martínez Araceli , Ortega Jorge E. , Galera-López Lorena , Hervera Arnau , Ortega-Álvaro Antonio , Remmers Floortje , Muñoz-Moreno Emma , Soria Guadalupe , del Río José Antonio , Lutz Beat , Ángel Ruíz-Ortega Jose , Meana J. Javier , Maldonado Rafael , Ozaita Andrés
Published: June 2021

Peripheral inputs to the brain continuously shape its function and can influence the formation of non-emotional memory, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptors (CB1R), widely distributed in the organism, is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing non-emotional memory in mice, we have now found a relevant role of peripheral CB1R in the formation of persistent memory. Indeed, peripherally restricted CB1R antagonism by using AM6545 showed a mnemonic effect that was occluded in adrenalectomized mice, after peripheral adrenergic blockade, or when vagus nerve was chemogenetically inhibited. Genetic CB1R deletion in dopamine β-hydroxylase-expressing cells enhanced the formation of persistent memory, supporting a role of peripheral CB1R modulating the adrenergic tone. Notably, brain connectivity was affected by peripheral CB1R inhibition, and locus coeruleus activity and extracellular hippocampal norepinephrine, were increased. In agreement, intra-hippocampal β-adrenergic blockade prevented AM6545 mnemonic effects. Together, we disclose a novel peripheral mechanism relevant for the modulation of the formation of persistent non-emotional memory.
Insights into early stages of the establishment of host:algal endosymbioses: Genetic responses to live versus heat-killed algae and bacterial prey in a sponge host
Authors: Camilli Sara , Koutsouveli Vasiliki , Hall Chelsea , Chang Lillian , Sacristan-Soriano Oriol , Hill Malcolm , Riesgo Ana , Hill April
Published: June 2021

The freshwater sponge Ephydatia muelleri and its Chlorella-like green algal partner is an emerging model for studying animal:algal endosymbiosis. The sponge host is a highly tractable laboratory organism, and the symbiotic algae are easily cultured. We took advantage of these traits to experimentally interrogate fundamental questions about cellular mechanisms that govern the establishment of durable intracellular partnerships between hosts and symbionts in facultative symbioses. We modified a classical experimental approach to discern the phagocytotic mechanisms that might be co-opted to permit persistent infections, and identified genes differentially expressed in E. muelleri sponges early in the establishment of endosymbiosis. We exposed algal-free E. muelleri to live native algal symbionts, native heat-killed algae, and bacteria, and then performed RNASeq so we could compare patterns of gene expression in each treatment. We contrasted differential gene expression patterns between potential food items (bacteria and heat-killed algae) and the live native Chlorella-like symbiont. We found a relatively small but interesting suite of genes that are uniquely and differentially expressed in the host exposed to live algal symbionts, and a larger number of genes uniquely triggered by host exposure to heat-killed algae. One of the host genes, an ABC transporter that is downregulated in response to live algal symbionts, was further evaluated for its possible role in establishment of the algal symbiosis. We discuss the gene expression profiles associated with host responses to living algal cells in the context of conditions necessary for long-term residency within host cells by phototrophic symbionts as well as the genetic responses to sponge phagocytosis and immune driven pathways.
Comparative proteome analysis revealed the differences in responses of bovine alveolar macrophages to both M.tb and Mb infection
Authors: Cai Yurong , Li Yong , Gao Weifeng , Wang Pu , Zhang Gang , Jiang Lingling
Published: June 2021

Bovine tuberculosis, caused by both MTB(Mycobacterium tuberculosis) and MB(Mycobacterium bovis), is one of the most serious zoonotic diseases in the world. Both pathogenic MTB and MB interact closely with the host alveolar macrophages. However, the mechanisms of defense response of macrophages to MTB or MB still need further researches. Presently, in-depth comparative proteome analysis was performed on the MB- and MTB- infected macrophage. We identified that macrophages was more sensitive to the MB infection. Both pathogens could induce strong energy metabolism of macrophages. To eliminate MB and protect the host, a bunch of proteins and signaling which involved in autophagy- and inflammatory-related progresses were highly activated in macrophages following MB infection. In contrast, only proteins relevant to energy metabolisms were highly expressed in macrophages following MTB infection. In summary, we proposed that macrophages were more sensitive to MB attacks and could deployed proteins functioned in autophagy- and inflammatory-related progresses to protect the host. Our research provide a novel insight into the different mechanisms of defense responses of macrophages to both MTB and MB infection.