bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi-centre, randomized, controlled trial on coaching and telemonitoring in patients with cystic fibrosis: conneCT CF
Authors: Thee Stephanie , Stahl Mirjam , Fischer Rainald , Sutharsan Sivagurunathan , Ballmann Manfred , Müller Axel , Lorenz Daniel , Urbanski-Rini Dominika , Püschner Franziska , Amelung Volker Eric , Fuchs Carola , Mall Marcus Alexander
Published: April 2021

Background

The extend of lung disease remains the most important prognostic factor for survival in patients with cystic fibrosis (CF), and lack of adherence is the main reason for treatment failure. Early detection of deterioration in lung function and optimising adherence are therefore crucial in CF care. We implement a randomized controlled trial to evaluate efficacy of telemonitoring of adherence, lung function, and health condition in combination with behavior change interventions using innovative digital technologies.

Methods

This is a multi-centre, randomized, controlled, non-blinded trial aiming to include 402 patients ≥ 12 years-of-age with CF. A standard-of-care arm is compared to an arm receiving objective, continuous monitoring of adherence to inhalation therapies, weekly home spirometry using electronic devices with data transmission to patients and caring physicians combined with video-conferencing, a self-management app and professional telephone coaching. The duration of the intervention phase is 18 months. The primary endpoint is time to the first protocol-defined pulmonary exacerbation. Secondary outcome measures include number of and time between pulmonary exacerbations, adherence to inhalation therapy, changes in forced expiratory volume in 1 s from baseline, number of hospital admissions, and changes in health-related quality of life. CF-associated medical treatment and care, and health care related costs will be assessed by explorative analysis in both arms.

Discussion

This study offers the opportunity to evaluate the effect of adherence interventions using telemedicine capable devices on adherence and lung health, possibly paving the way for implementation of telemedicine in routine care for patients with CF.

Trial registration: This study has been registered with the German Clinical Trials Register (Identifier: DRKS00024642, date of registration 01 Mar 2021, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024642).
Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy
Authors: Julià Antonio , López-Lasanta María , Blanco Francisco , Gómez Antonio , Haro Isabel , Mas Antonio Juan , Erra Alba , Vivar Ma Luz García , Monfort Jordi , Sánchez-Fernández Simón , González Isidoro , Alperi Mercedes , Castellanos-Moreira Raúl , Fernández-Nebro Antonio , Díaz-Torné César , Palau Núria , Lastra Raquel , Lladós Jordi , Sanmartí Raimon , Marsal Sara
Published: April 2021

Background

Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50–60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy.

Methods

For this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age.

Results

The interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04).

Conclusions

The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA.
Knowledge, attitudes, and practices of cervical cancer prevention and pap smears in two low-income communities in Lima, Peru
Authors: Miles Thomas T. , Riley-Powell Amy R. , Lee Gwenyth O. , Gotlieb Esther E. , Barth Gabriela C. , Tran Emma Q. , Ortiz Katherine , Huaynate Cynthia Anticona , Cabrera Lilia , Gravitt Patti E. , Oberhelman Richard A. , Paz-Soldan Valerie A.
Published: April 2021

Background

Cervical cancer is a leading cause of death among Peruvian women. Barriers at multiple levels impact effective screening and treatment, including a lack of knowledge about cervical cancer and how regular screening can reduce morbidity and mortality through earlier detection. The aim of this study is to assess knowledge, attitudes, and practices regarding cervical cancer and its prevention in the peri-urban communities of Oasis and Pampas in southern Lima, Peru that can be used to inform future campaigns about cervical cancer prevention.

Methods

A cross-sectional survey that included several open-ended questions was administered to women in Pampas and Oasis between 2015 and 2016 to evaluate the knowledge, attitudes, and practices regarding cervical cancer and Pap smears.

Results

In total, 224 women were interviewed. Knowledge about cervical cancer and Pap smears was high, and attitudes were predominantly positive among most participants. Most participants knew how often they should get Pap smears (89.7%), when to begin seeking screening (74.6%), knew the price of a Pap smear (61.9%), and felt Pap smears were important for their health (70.1%). About one third (29.5%) of premenopausal women reported receiving a Pap smear in the last year. However, open ended questions revealed some knowledge gaps around Pap smears, as well as some stigma associated to Human Papilloma Virus (HPV) infection.

Conclusion

Although knowledge of cervical cancer prevention was generally high and perceptions were positive among women in peri-urban Peruvian communities, our findings revealed there is a need for education on HPV infection prevalence among sexually active individuals to reduce stigma. Future research should focus on exploring experiences with follow-up and treatment associated with abnormal Pap smears, as well as perspectives from health authorities and professionals about barriers in the early detection and treatment process for cervical cancer.
Patient-reported dyspnea and health predict waitlist mortality in patients waiting for lung transplantation in Japan
Authors: Ikeda Masaki , Oga Toru , Chen-Yoshikawa Toyofumi F. , Tokuno Junko , Oto Takahiro , Okawa Tomoyo , Okada Yoshinori , Akiba Miki , Tanaka Satona , Yamada Yoshito , Yutaka Yojiro , Ohsumi Akihiro , Nakajima Daisuke , Hamaji Masatsugu , Isomi Maki , Chin Kazuo , Date Hiroshi
Published: April 2021

Background

Waitlist mortality due to donor shortage for lung transplantation is a serious problem worldwide. Currently, the selection of recipients in Japan is mainly based on the registration order. Hence, scientific evidence for risk stratification regarding waitlist mortality is urgently needed. We hypothesized that patient-reported dyspnea and health would predict mortality in patients waitlisted for lung transplantation.

Methods

We analyzed factors related to waitlist mortality using data of 203 patients who were registered as candidates for lung transplantation from deceased donors. Dyspnea was evaluated using the modified Medical Research Council (mMRC) dyspnea scale, and the health status was determined with St. George’s Respiratory Questionnaire (SGRQ).

Results

Among 197 patients who met the inclusion criteria, the main underlying disease was interstitial lung disease (99 patients). During the median follow-up period of 572 days, 72 patients died and 96 received lung transplantation (69 from deceased donors). Univariable competing risk analyses revealed that both mMRC dyspnea and SGRQ Total score were significantly associated with waitlist mortality (p = 0.003 and p < 0.001, respectively) as well as age, interstitial lung disease, arterial partial pressure of carbon dioxide, and forced vital capacity. Multivariable competing risk analyses revealed that the mMRC and SGRQ score were associated with waitlist mortality in addition to age and interstitial lung disease.

Conclusions

Both mMRC dyspnea and SGRQ score were significantly associated with waitlist mortality, in addition to other clinical variables such as patients’ background, underlying disease, and pulmonary function. Patient-reported dyspnea and health may be measured through multi-dimensional analysis (including subjective perceptions) and for risk stratification regarding waitlist mortality.
IFN-λ4 genetic variants influence clinical malaria episodes in a cohort of Kenyan children
Authors: Samayoa-Reyes Gabriela , Jackson Conner , Ogolla Sidney , Sabourin Katherine , Obajemu Adeola , Dent Arlene E. , Prokunina-Olsson Ludmilla , Rochford Rosemary
Published: April 2021

Background

Interferon (IFN)- λ4, a type III IFN, production is controlled by a dinucleotide frameshift variant (rs368234815-dG/TT) within the first exon of the IFNL4 gene. Carriers of the IFNL4-dG allele but not the IFNL4-TT allele are able to produce the IFN-λ4 protein. Patients with hepatitis C virus that do not produce the IFN-λ4 protein have higher rates of viral clearance suggesting a potential inhibitory role of IFN-λ4 in liver-tropic infections.

Methods

In this study, it was investigated whether children infected with Plasmodium falciparum, which has a well-characterized liver stage infection, would be more susceptible to clinical malaria relative to their IFNL4-rs368234815 allele. A cohort of 122 children from a malaria holoendemic region of Kenya was analysed. Episodes of clinical malaria and upper respiratory tract infections (URTIs) were determined using information collected from birth to 2 years of age. The dinucleotide frameshift variant IFNL4-rs368234815-dG/TT was genotyped using a TaqMan assay.

Results

In this cohort, 33% of the study participants had the dG/dG genotype, 45% had the dG/TT genotype, and 22% had TT/TT genotype. The number and time to first episode of clinical malaria and URTIs with respect to the IFNL4-rs368234815 allele was evaluated. It was found that children that carried the IFNL4-rs368234815-dG allele had an increased number of clinical malaria episodes. In addition, there was a significant association between earlier age of first malaria infection with carriers of the IFNL4-dG allele (p-value: 0.021).

Conclusion

The results suggest that the ability to produce IFN-λ4 negatively affects host immune protection against P. falciparum malaria in Kenyan children.
Hospital admissions and mortality due to complications of injection drug use in two hospitals in Regina, Canada: retrospective chart review
Authors: Tsybina Polina , Kassir Sandy , Clark Megan , Skinner Stuart
Published: April 2021

Background

Infectious complications of injection drug use (IDU) often require lengthy inpatient treatment. Our objective was to identify the number of admissions related to IDU in Regina, Canada, as well as describe patient demographics and comorbidities, yearly mortality, readmission rate, and cumulative cost of these hospitalizations between January 1 and December 31, 2018. Additionally, we sought to identify factors that increased risk of death or readmission.

Methods

This study is a retrospective chart review conducted at the two hospitals in Regina. Eligible study cases were identified by querying the discharge database for predetermined International Classification of Diseases code combinations. Electronic medical records were reviewed to assess whether each admission met inclusion criteria, and hospitalization and patient data were subsequently extracted for all included admissions. Mortality data were gleaned from hospital and Ministry of Health databases. Data were analyzed using Excel and IBM SPSS Statistics to identify common comorbidities, admission diagnoses, and costs, as well as to compare patients with a single admission during the study period to those with multiple admissions. Logistic regression analysis was used to identify the relationship between individual variables and in- and out-of-hospital annual mortality.

Results

One hundred and forty-nine admissions were included, with 102 unique patients identified. Common comorbidities included hepatitis C (47%), human immunodeficiency virus (HIV) (25%), and comorbid psychiatric disorders (19%). In 23% of all admissions, patients left hospital prior to treatment completion, and 27% of patients experienced multiple admissions. Female patients and those with chronic pain were more likely to be readmitted (p = 0.024 and p = 0.029, respectively). Patients admitted with infective endocarditis were more likely to die during hospitalization (p = 0.0001). The overall mortality was 15% in our cohort. The estimated cumulative cost of inpatient treatment of complications of IDU in Regina was $3.7 million CAD in 2018.

Conclusion

Patients with history of IDU and hospital admission experience high mortality rates in Regina, a city with paucity of inpatient supports for persons who use injection drugs. Needle syringe programs, opioid agonist therapy, and safe consumption sites have been shown to improve outcomes as well as reduce healthcare costs for this patient population. We will use our findings to advocate for increased access to these harm reduction strategies in Regina, particularly for inpatients.
Correction to: The cross-sectional average length of healthy life (HCAL): a measure that summarizes the history of cohort health and mortality
Authors: Sauerberg Markus , Guillot Michel , Luy Marc
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis
Authors: Mesic Anita , Spina Alexander , Mar Htay Thet , Thit Phone , Decroo Tom , Lenglet Annick , Thandar Moe Pyae , Thwe Thin Thin , Kyaw Aung Aung , Homan Tobias , Sangma Mitchell , Kremer Ronald , Grieg Jane , Piriou Erwan , Ritmeijer Koert , Van Olmen Josefien , Lynen Lutgarde , Oo Htun Nyunt
Published: April 2021

Background

Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar.

Methods

We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months’ standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox’s regression was performed to identify risk factors for virological failure.

Results

We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0–39.1) and a median observation time of 5.4 years (IQR 3.7–7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20–1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14–1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42–1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41–1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07–1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates.

Conclusions

VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.
Fecal carriage of extended spectrum beta-lactamase producing Enterobacteriaceae among HIV infected children at the University of Gondar Comprehensive Specialized Hospital Gondar, Ethiopia
Authors: Bayleyegn Biruk , Fisaha Roman , Kasew Desie
Published: April 2021

Background

Human immunodeficiency virus (HIV) and extended spectrum beta lactamase (ESBL) producing Enterobacteriaceae infections are the major challenges in sub-Saharan Africa. Data on the carriage rate of ESBL producing Enterobacteriaceae among HIV infected children is lacking in Ethiopia. Hence this study was aimed to investigate fecal carriage of ESBL producing Enterobacteriaceae among HIV infected children at the University of Gondar comprehensive Specialized Hospital.

Methods

A cross-sectional study was conducted among HIV infected children from January to April 2020. Stool specimens were collected from 161 study participants by convenient sampling and cultured on MacConkey agar. Biochemical identification, antimicrobial susceptibility testing including ESBL production were carried out. Data were analyzed by SPSS version-20 and P-value < 0.05 on multivariate logistic regression analysis was regarded as statistically significant.

Results

From a total of 161 study participants male to female ratio was 1:1.1. Moreover; 96.3% of participants were in HIV stage-I and 90.1% had at least a year highly active antiretroviral therapy exposure. A total of 186 Enterobacteriaceae, withE. coli60% andK. pneumonia16.13% predominance were isolated from 161 participants. Majority of isolates were most resistant to amoxicillin (95.1%) and sensitive to CHL (94.1%), CXT (91.4%) and CAZ (91.4%). There were 71(38.17%) multidrug resistant isolates, 13 of which were also ESBL producers. The overall ESBL carriage rate was 32/161 (19.9%). History of antibiotic use was the independent factor associated with ESBL carriage (AOR 3.23 (95% CI 1.054–9.88)) and P-value of 0.04.

Conclusion

ESBL carriage rate of HIV infected children was considerable. Previous antibiotic use was the independent factor. Regular screening for antibiotic resistance on HIV patients before prescription and large-scale antibiotic resistance survey including healthy community may be important.
Exploiting telerobotics for sensorimotor rehabilitation: a locomotor embodiment
Authors: Koh Min Hyong , Yen Sheng-Che , Leung Lester Y. , Gans Sarah , Sullivan Keri , Adibnia Yasaman , Pavel Misha , Hasson Christopher J.
Published: April 2021

Background

Manual treadmill training is used for rehabilitating locomotor impairments but can be physically demanding for trainers. This has been addressed by enlisting robots, but in doing so, the ability of trainers to use their experience and judgment to modulate locomotor assistance on the fly has been lost. This paper explores the feasibility of a telerobotics approach for locomotor training that allows patients to receive remote physical assistance from trainers.

Methods

In the approach, a trainer holds a small robotic manipulandum that shadows the motion of a large robotic arm magnetically attached to a locomoting patient's leg. When the trainer deflects the manipulandum, the robotic arm applies a proportional force to the patient. An initial evaluation of the telerobotic system’s transparency (ability to follow the leg during unassisted locomotion) was performed with two unimpaired participants. Transparency was quantified by the magnitude of unwanted robot interaction forces. In a small six-session feasibility study, six individuals who had prior strokes telerobotically interacted with two trainers (separately), who assisted in altering a targeted gait feature: an increase in the affected leg’s swing length.

Results

During unassisted walking, unwanted robot interaction forces averaged 3−4 N (swing–stance) for unimpaired individuals and 2−3 N for the patients who survived strokes. Transients averaging about 10 N were sometimes present at heel-strike/toe-off. For five of six patients, these forces increased with treadmill speed during stance (R2 = .99; p < 0.001) and increased with patient height during swing (R2 = .71; p = 0.073). During assisted walking, the trainers applied 3.0 ± 2.8 N (mean ± standard deviation across patients) and 14.1 ± 3.4 N of force anteriorly and upwards, respectively. The patients exhibited a 20 ± 21% increase in unassisted swing length between Days 1−6 (p = 0.058).

Conclusions

The results support the feasibility of locomotor assistance with a telerobotics approach. Simultaneous measurement of trainer manipulative actions, patient motor responses, and the forces associated with these interactions may prove useful for testing sensorimotor rehabilitation hypotheses. Further research with clinicians as operators and randomized controlled trials are needed before conclusions regarding efficacy can be made.
Antiviral Activities of a Medicinal Plant Extract Against Sacbrood Virus in Honeybees
Authors: Sun Liping , Zhang Xueqi , Xu Shufa , Hou Chunsheng , Xu Jin , Zhao Dongxiang , Chen Yanping
Published: April 2021

Background

Sacbrood is an infectious disease of the honey bee caused by Scbrood virus (SBV) which belongs to the family Iflaviridae and is especially lethal for Asian honeybee Apis cerana. Chinese Sacbrood virus (CSBV) is a geographic strain of SBV. Currently, there is a lack of an effective antiviral agent for controlling CSBV infection in honey bees.

Methods

Here, we explored the antiviral effect of a Chinese medicinal herb Radix isatidis on CSBV infection in A. cerana by inoculating the 3rd instar larvae with purified CSBV and treating the infected bee larvae with R. isatidis extract at the same time. The growth, development, and survival of larvae between the control and treatment groups were compared. The CSBV copy number at the 4th instar, 5th instar, and 6th instar larvae was measured by the absolute quantification PCR method.

Results

Bioassays revealed that R. isatidis extract significantly inhibited the replication of CSBV, mitigated the impacts of CSBV on larval growth and development, reduced the mortality of CSBV-infected A. cerana larvae, and modulated the expression of immune transcripts in infected bees.

Conclusion

Although the mechanism underlying the inhibition of CSBV replication by the medicine plant will require further investigation, this study demonstrated the antiviral activity of R. isatidis extract and provides a potential strategy for controlling SBV infection in honey bees.
Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans
Authors: Ram Heera , Kumar Pramod , Purohit Ashok , Kashyap Priya , Kumar Suresh , Kumar Shivani , Singh Garima , Alqarawi Abdulaziz A. , Hashem Abeer , Abd-Allah Elsayed Fathi , Al-Arjani Al-Bandari Fahad , Singh Bhim Pratap
Published: April 2021

Context

Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes.

Objective

The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of W. coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities.

Material and methods

The identification of phytoconstituents of the test extract was performed by LCMS. Further, assessments of in-vitro, in-vivo and in-silico were achieved by following standard methods. In-vivo studies were conducted on type-2 diabetic rats.

Results

The chosen extract inhibited DPP-4 activity by 63.2% in an in vitro assay as well as significantly inhibit serum DPP-4 levels. Accordingly, the administration of the ethanol fruit extract resulted in a significant (P ≤ 0.001) alterations in the lipid profile, antioxidant levels, and HOMA indices. Moreover, pancreatic endocrinal tissues (islet of Langerhans) appeared to have the restoration of normal histoarchitecture as evidenced by increased cellular mass. Molecular docking (Protein-ligands) of identified phytoconstituents with DPP-4 (target enzyme) shown incredibly low binding energy (Kcal/mol) as required for ideal interactions. ADMET analysis of the pharmacokinetics of the identified phytoconstituents indicated an ideal profile as per Lipinski laws.

Conclusion

It can be concluded that the phytoconstituents of an ethanol fruit extract of W. coagulans have the potential to inhibit DPP-4 which result in improved glucose homeostasis and restoration of pancreatic endocrinal tissues in type-2 diabetic rats.
Rhinocerebral mucormycosis secondary to severe acute pancreatitis and diabetic ketoacidosis: a case report
Authors: Wang Jinjing , Li Yao , Luo Shuai , Zheng Hong
Published: April 2021

Introduction

Rhinocerebral mucormycosis is a rare and severe form of opportunistic fungal infection that can develop rapidly and cause significant mortality, particularly among diabetic patients suffering from ketoacidosis. Diagnosing rhinocerebral mucormycosis during the early stages of infection is challenging.

Case presentation

We describe a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis. In this case, the condition was not diagnosed during the optimal treatment window. we therefore provide a thorough overview of related clinical findings and histopathological characteristics, and we discuss potential differential diagnoses.

Conclusions

In summary, we described a case of rhinocerebral mucormycosis secondary to severe acute pancreatitis in a patient suffering from diabetic ketoacidosis, with the optimal treatment window for this condition having been missed. This report suggests that a definitive mucormycosis diagnosis can be made based upon tissue biopsy that reveals the presence of characteristic hyphae. Early diagnosis and treatment are essential in order to improve patient prognosis.
Surgical treatment for patients with hemophilic pseudotumor-related femoral fracture: a retrospective study
Authors: Chen Keyu , Jiang Guiyong , Xu Yaowen , Yang Yunping , Mao Zexiong , Lv Jiaxin , Liu Fei , Chen Bin
Published: April 2021

Background

Hemophilic pseudotumor (HPT)-related fracture is a rare but severe complication in patients with HPTs. These fractures often occur in femurs. There is no consensus on the standard surgical protocol for HPT-related femoral fracture. The present retrospective study evaluated the outcomes of these patients treated with surgical interventions.

Methods

Ten patients with HPT-related femoral fractures who were treated with 14 surgical procedures due to 11 fractures in our hospital from January 2014 to April 2020 were evaluated retrospectively. Demographic data, fracture location, complications after surgery, and follow-up outcomes were recorded and analyzed. The mean follow-up period was 39.7 months.

Results

The mean age at surgery was 31 years. Closed reduction external fixation (CREF) was originally performed in 2 patients, open reduction internal fixation (ORIF) was performed in 4 patients, screw fixation alone was performed in 1 patient, brace immobilization was performed in 1 patient, and amputation was performed in 3 patients. Bone union was observed in 5 patients, and an adequate callus was visible in 2 patients. Both patients with CREF had pin infections. Nonunion combined with external fixation (EF) failure occurred in 1 patient, and the plate was broken after ORIF. Three patients underwent autogenous or allogeneic cortical strut grafting. Three patients had HPT recurrence.

Conclusions

It is necessary to perform surgery in patients with HPT-related femoral fractures. Surgical treatments must consider fracture stabilization and HPT resection. Internal fixation is preferable, and EF should only be used for temporary fixation. If the HPT erodes more than one third of the bone diameter, strut grafts are necessary for mechanical stability. Amputation is an appropriate curative method in certain situations.
Dexmedetomidine combined with sufentanil and dezocine-based patient-controlled intravenous analgesia increases female patients’ global satisfaction degree after thoracoscopic surgery
Authors: Li Qiongzhen , Yao Haixia , Xu Meiying , Wu Jingxiang
Published: April 2021

Background

There are no studies on the use of dexmedetomidine combined with sufentanil and dezocine-based patient-controlled intravenous analgesia (PCIA) in females undergoing thoracic surgery. We postulate that introducing dexmedetomidine to a combination of dezocine-based PCA drugs and sufentanil will increase female patients’ global satisfaction degree.

Methods

One hundred fifty-two female patients with physical classification type I or II according to the American Society of Anesthesiologists undergoing thoracoscopic surgery were arbitrarily classified into two categories, either receiving sufentanil and dezocine-based PCIA (group C) or incorporating dexmedetomidine with sufentanil and dezocine-based PCIA (group D). The patients’ global satisfaction degree, postoperative nausea and vomiting (PONV), PCA bolus, rescue analgesia requirements, drug-related adverse effects, rest and coughing visual analogue scale (VAS) ratings, and Ramsay sedation scores (RSS) were measured at 6, 12, 24, 36 and 48 h after surgery.

Results

Compared with the C group, the patient satisfaction degree was significantly higher; pain scores at rest and coughing were significantly different at 6, 12, 24, 36 and 48 h postoperatively; less rescue analgesia and PCA bolus were required; and a lower incidence of PONV was found in the D group. There were non-significant trends for the sedation scores and drug-related adverse effects in both groups.

Conclusions

Dexmedetomidine combined with sufentanil and dezocine increased female patients’ global satisfaction degree after thoracoscopic surgery. This effect could be linked to the improvement in postoperative analgesia and reduction in postoperative nausea and vomiting; the combined treatment did not increase drug-related adverse effects in female patients.

Trial registration

Chinese Clinical Trial Registry number, ChiCTR2000030429. Registered on March 1, 2020.
New stent for transapical mitral valve replacement in acute swine experiment
Authors: Zou Yu , Teng Peng , Ma Liang
Published: April 2021

Background

Many patients with mitral regurgitation are denied open-heart surgery due to perceived high risk. Transcatheter mitral valve replacement is a therapeutic alternative for patients at high surgical risk. This study aimed to assess the feasibility of a new self-expanding valved stent for transcatheter mitral valve replacement via apex in an acute animal model.

Methods

Eight porcine experiments were performed in the acute study. A left thoracotomy was performed, and the new self-expanding transcatheter valved stent was deployed under fluoroscopic guidance in the native mitral annulus via apex. Hemodynamic data were recorded before and after implantation. Mitral annulus diameter and valve area were measured using echocardiography. Transvalvular and left ventricular outflow tract pressure gradients were measured using invasive methods.

Results

Seven animals underwent successful transapical mitral valve replacement; the implantation was unsuccessful in one animal. The mean procedure time, defined from placement to tightening of the purse-string suture, was 17.14 ± 7.86 min. Hemodynamic data before and after transapical mitral valve replacement showed no difference in statistical analysis. The mean diameter of the self-expanding device after implantation was 2.58 ± 1.04 cm; the mean functional area was 2.70 ± 0.26 cm2. Trace-to-mild central and paravalvular leaks were detected in 7 valves. The mean pressure gradient across the self-expanding device was 2.00 ± 0.82 mmHg; the corresponding gradient across the LVOT was 3.28 ± 1.11 mmHg. Postmortem evaluation confirmed precise device positioning in 7 animals with no signs of LVOT obstruction.

Conclusion

Transcatheter mitral replacement of the new valved stent was confirmed feasible in acute preclinical models. The new stent reveals optimal design parameters.
Beyond association: successes and challenges in linking non-coding genetic variation to functional consequences that modulate Alzheimer’s disease risk
Authors: Novikova Gloriia , Andrews Shea J. , Renton Alan E. , Marcora Edoardo
Published: April 2021

Alzheimer’s disease (AD) is the most common type of dementia, affecting millions of people worldwide; however, no disease-modifying treatments are currently available. Genome-wide association studies (GWASs) have identified more than 40 loci associated with AD risk. However, most of the disease-associated variants reside in non-coding regions of the genome, making it difficult to elucidate how they affect disease susceptibility. Nonetheless, identification of the regulatory elements, genes, pathways and cell type/tissue(s) impacted by these variants to modulate AD risk is critical to our understanding of disease pathogenesis and ability to develop effective therapeutics. In this review, we provide an overview of the methods and approaches used in the field to identify the functional effects of AD risk variants in the causal path to disease risk modification as well as describe the most recent findings. We first discuss efforts in cell type/tissue prioritization followed by recent progress in candidate causal variant and gene nomination. We discuss statistical methods for fine-mapping as well as approaches that integrate multiple levels of evidence, such as epigenomic and transcriptomic data, to identify causal variants and risk mechanisms of AD-associated loci. Additionally, we discuss experimental approaches and data resources that will be needed to validate and further elucidate the effects of these variants and genes on biological pathways, cellular phenotypes and disease risk. Finally, we discuss future steps that need to be taken to ensure that AD GWAS functional mapping efforts lead to novel findings and bring us closer to finding effective treatments for this devastating disease.
Human immunodeficiency virus-related renal cell carcinoma: a retrospective study of 19 cases
Authors: Zhang Mengmeng , Zhu Zhiqiang , Xue Wenrui , Liu Hui , Zhang Yu
Published: April 2021

Purpose

We aimed to investigate basic information, clinical findings, treatments for tumor, pathology, and outcomes of HIV-positive patients diagnosed with renal cell carcinoma (RCC).

Patients and methods

We collected 19 patients from 2012 to 2020 who are diagnosed with RCC with HIV-positive. A retrospective analysis was performed on their hospitalization course and tumor-related parameters, including basic information, clinical findings, HIV-associated data, pathology, treatments for tumor, and outcomes.

Results

In our study, patients were diagnosed with RCC at the median age of 51. Males took a great part (17 males, 89%) in all patients, while only 2 females were diagnosed. The median CD4+ T lymphocyte cell count was 462 cells/μl when diagnosed with RCC (range from 111 cells/μl to 1536 cells/μl). Eleven patients diagnosed with RCC and HIV infection at the same time, who may have high viral load and low CD4+ T lymphocyte cell count. Eight patients accepted a median HAART for 30 months (range from 11 months to 108 months) prior to diagnosis of RCC. All the patients performed operations successfully, and 4 of them performed partial nephrecotomy. Only 1 patient was identified with chromophobe cell carcinoma, 1 with partially clear cell and partially papillary carcinoma, and 17 with clear cell carcinoma. Two of the patients with Fuhrman grades 2–3 accepted cytokine therapy with IL-2 and IFN-α. Two patients died of lung metastasis 1 year and 6 months after surgery respectively, even though 1 patient accepted full dose targeted therapy (sorafenib) for 3 months, and one refused adjuvant therapy. The remaining 17 patients are still alive at a median follow-up of 34 months; however, 1 patient lives with lung and brain metastases at the last follow-up of 3 years after surgery.

Conclusions

RCC patients with HIV-positive were similar to the general population in terms of clinical characters, treatment measures, and pathology. RCC patients with HIV-positive seemed like to obey the same clinical practice guideline as in the general population. The outcomes of HIV-positive patients with partial nephrectomy are not inferior to patients with radical nephrectomy. Furthermore, experience in targeted therapy and immunal therapy (PD-1/PD-L1 inhibitors) needs to be learned.
In vitro recellularization of decellularized bovine carotid arteries using human endothelial colony forming cells
Authors: Seiffert Nicolai , Tang Peter , Keshi Eriselda , Reutzel-Selke Anja , Moosburner Simon , Everwien Hannah , Wulsten Dag , Napierala Hendrik , Pratschke Johann , Sauer Igor M. , Hillebrandt Karl H. , Struecker Benjamin
Published: April 2021

Background

Many patients suffering from peripheral arterial disease (PAD) are dependent on bypass surgery. However, in some patients no suitable replacements (i.e. autologous or prosthetic bypass grafts) are available. Advances have been made to develop autologous tissue engineered vascular grafts (TEVG) using endothelial colony forming cells (ECFC) obtained by peripheral blood draw in large animal trials. Clinical translation of this technique, however, still requires additional data for usability of isolated ECFC from high cardiovascular risk patients.

Bovine carotid arteries (BCA) were decellularized using a combined SDS (sodium dodecyl sulfate) -free mechanical-osmotic-enzymatic-detergent approach to show the feasibility of xenogenous vessel decellularization. Decellularized BCA chips were seeded with human ECFC, isolated from a high cardiovascular risk patient group, suffering from diabetes, hypertension and/or chronic renal failure. ECFC were cultured alone or in coculture with rat or human mesenchymal stromal cells (rMSC/hMSC). Decellularized BCA chips were evaluated for biochemical, histological and mechanical properties. Successful isolation of ECFC and recellularization capabilities were analyzed by histology.

Results

Decellularized BCA showed retained extracellular matrix (ECM) composition and mechanical properties upon cell removal. Isolation of ECFC from the intended target group was successfully performed (80% isolation efficiency). Isolated cells showed a typical ECFC-phenotype. Upon recellularization, co-seeding of patient-isolated ECFC with rMSC/hMSC and further incubation was successful for 14 (n = 9) and 23 (n = 5) days. Reendothelialization (rMSC) and partial reendothelialization (hMSC) was achieved. Seeded cells were CD31 and vWF positive, however, human cells were detectable for up to 14 days in xenogenic cell-culture only. Seeding of ECFC without rMSC was not successful.

Conclusion

Using our refined decellularization process we generated easily obtainable TEVG with retained ECM- and mechanical quality, serving as a platform to develop small-diameter (< 6 mm) TEVG. ECFC isolation from the cardiovascular risk target group is possible and sufficient. Survival of diabetic ECFC appears to be highly dependent on perivascular support by rMSC/hMSC under static conditions. ECFC survival was limited to 14 days post seeding.
Ventilator-associated pneumonia in the era of COVID-19 pandemic: How common and what is the impact?
Authors: Wicky Paul-Henri , Niedermann Michael S. , Timsit Jean-François
Published: April 2021

We reviewed similarities and differences of ventilator associated pneumonia in Sars-Cov2 infection and with other ARDS. The differences in epidemiology and outcome will be detailed. Possible explanations of differences in pathophysiology of VAP in Sarscov2 infections will be cited and discussed.
Enhanced PeriOperative Care and Health protection programme for the prevention of surgical site infections after elective abdominal surgery (EPO2CH): statistical analysis plan of a randomised controlled multicentre superiority trial
Authors:   for the EPO2CH study group, de Jonge S. W. , Wolfhagen N. , Zwinderman A. H. , Hollmann M. W. , Boermeester M. A. , Dijkgraaf M. G. W.
Published: April 2021

Background

Surgical site infections (SSI) are frequent complications after elective abdominal surgery. We designed the Enhanced PeriOperative Care and Health Protection programme (EPO2CH) care bundle, comprising of intraoperative high fractional inspired oxygen; intraoperative goal-directed fluid therapy; active preoperative, intraoperative and postoperative warming; glucose control and treatment of hyperglycaemia (> 10 mmol L− 1) in diabetics as well as non-diabetics; and wound irrigation before closure using an aqueous antiseptic. We hypothesise that EPO2CH added to standard care reduces the incidence of SSI compared to standard care alone for elective abdominal surgery.

Methods

This trial is designed as an open label, pragmatic randomised controlled parallel-group multicentre superiority trial. The primary endpoint is the incidence of SSI, defined by the Centers for Disease Control and prevention, within 30 days after surgery. The incidence of SSI is assessed using the Dutch national complication register and medical chart review. Secondary endpoints include the SSI incidence within 90 days, incidence of anastomotic leakage at 30 and 90 days, the incidence of incisional hernia within 1 year, mortality within 1 year and 5 years, quality of life, health and disability, and cost-effectiveness. Primarily, an intention-to-treat analysis will be performed to estimate the relative risk using a log binomial model. If not feasible, a logistic regression will be used to estimate the odds ratio. A per-protocol analysis will also be performed. Furthermore, the attributive effect of the distinct interventions will be explored.

Discussion

The results of the EPO2CH trial will determine if the EPO2CH bundle is effective to prevent SSI incidence for patients undergoing elective abdominal surgery. Details of the statistical analysis are described in this Statistical Analysis Plan (SAP).

Trial registration

Registration number: Dutch Trial Register Trial NL5572. Registered on March 3, 2016.

SAP version: V1.0, January 8, 2020. This SAP has been written based on study protocol V10.
Multisite transcranial direct current stimulation associated with cognitive training in episodic memory and executive functions in individuals with Alzheimer’s disease: a case report
Authors: Marchi Letícia Zanetti , Ferreira Rayssa Gabriela Dantas , de Lima Gabriella Nayara Siqueira , da Silva Jessyca Alves Silvestre , da Cruz Daniel Marinho Cezar , Fernandez-Calvo Bernardino , Andrade Suellen Mary Marinho dos Santos
Published: April 2021

Background

Dementia is among the most common chronic noncommunicable neurodegenerative diseases. In the long term, it causes disability and loss of autonomy and independence. It is estimated that there are 35.6 million people with Alzheimer’s disease worldwide. Several clinical aspects of this disease have been widely studied, but the main focus of study has been memory loss, which is one of the first symptoms. The present study proposes an innovative intervention that combines cognitive training and multisite transcranial direct current stimulation, which interferes with other clinical aspects of the subject.

Case presentation

In this study, we present two subjects diagnosed with mild Alzheimer’s disease. Subject 1 is an 82-year-old Brazilian Latin American woman with a high school education who was diagnosed with Alzheimer’s disease 8 years ago and uses an Exelon patch. Subject 2 is an 88-year-old Brazilian Latin American woman with an incomplete primary education who was diagnosed with Alzheimer’s disease 1 year ago and received medical orientation to temporarily discontinue medications for Alzheimer’s disease. Both participants were subjected to intermittent cognitive training sessions and concomitant transcranial stimulation in three weekly 30-minute sessions in which a brain area was stimulated every 10 minutes for a total of 24 sessions, with a 2-month follow-up. Transcranial stimulation was applied to six different regions of the cortex: the dorsolateral prefrontal cortex bilaterally, the somatosensory association cortex bilaterally and Broca’s and Wernicke’s areas. Comparing the results of tests performed before and after the treatment period, a 1-point improvement was observed for both subjects on the Word Recall task of the Alzheimer Disease Assessment Scale, which evaluates symptoms related to the decline of episodic memory. Improvement in the executive functions domain was also observed through the results of the Stroop test, Victoria version.

Conclusions

The results from the two presented cases show that multisite transcranial stimulation associated with cognitive training is an effective adjuvant method for the treatment of patients diagnosed with mild Alzheimer’s disease. Its effects can benefit patients’ daily routines by reducing cognitive deficits by keeping intact areas active and/or compensating for lost functions.

Trial registration NCT02772185. Registered 13 May 2016, http://www.clinicaltrials.gov/ct2/show/NCT02772185. Retrospectively registered.
Efficient differentiation of human embryonic stem cells to retinal pigment epithelium under defined conditions
Authors: Limnios Ioannis J. , Chau Yu-Qian , Skabo Stuart J. , Surrao Denver C. , O’Neill Helen C.
Published: April 2021

Age-related macular degeneration (AMD) is a highly prevalent form of blindness caused by loss death of cells of the retinal pigment epithelium (RPE). Transplantation of pluripotent stem cell (PSC)-derived RPE cells is considered a promising therapy to regenerate cell function and vision.

Objective

The objective of this study is to develop a rapid directed differentiation method for production of RPE cells from PSC which is rapid, efficient, and fully defined and produces cells suitable for clinical use.

Design

A protocol for cell growth and differentiation from hESCs was developed to induce differentiation through screening small molecules which regulated a primary stage of differentiation to the eyefield progenitor, and then, a subsequent set of molecules to drive differentiation to RPE cells. Methods for cell plating and maintenance have been optimized to give a homogeneous population of cells in a short 14-day period, followed by a procedure to support maturation of cell function.

Results

We show here the efficient production of RPE cells from human embryonic stem cells (hESCs) using small molecules in a feeder-free system using xeno-free/defined medium. Flow cytometry at day 14 showed ~ 90% of cells expressed the RPE markers MITF and PMEL17. Temporal gene analysis confirmed differentiation through defined cell intermediates. Mature hESC-RPE cell monolayers exhibited key morphological, molecular, and functional characteristics of the endogenous RPE.

Conclusion

This study identifies a novel cell differentiation process for rapid and efficient production of retinal RPE cells directly from hESCs. The described protocol has utility for clinical-grade cell production for human therapy to treat AMD.