bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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).

Summary
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.
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

ABSTRACTObjectivesTo 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.DesignMulticentre, parallel efficacy, randomized, controlled, open label, assessor blind, exploratory trial with a convenience sample. Patients followed to complete 12 weeks of study duration.SettingCOVID-19 dedicated non-intensive care wards at 1 government hospital, 1 medical college teaching hospital and 1 medical university teaching hospitalParticipants140 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.InterventionsTwo 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 measuresTime period to clinical recovery (CR) from randomization baseline and proportion with CR within 28 days time frame; CR defined in the protocolResults140 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.ConclusionsAYUSH 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 registrationThe Clinical Trials Registry India Number CTRI/2020/06/025557FundingCCRAS, Ministry of AYUSH, Government of India