bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial distance between sites of sampling associated with genetic variation among Neospora caninum in aborted bovine foetuses from northern Italy
Authors: Villa Luca , Maksimov Pavlo , Luttermann Christine , Tuschy Mareen , Gazzonis Alessia L. , Zanzani Sergio A. , Mortarino Michele , Conraths Franz J. , Manfredi Maria Teresa , Schares Gereon
Published: January 2021

Background

Neospora caninum, a coccidian protozoan, represents an important cause of bovine abortion. AvailableN. caninumstrains show considerable variationin vitroandin vivo, including different virulence in cattle. To which extent sexual recombination, which is possible in the intestines of domestic dogs and closely related carnivores as definitive hosts, contributes to this variation is not clear yet.

Methods

Aborted bovine foetuses were collected between 2015 and early 2019 from Italian Holstein Friesian dairy herds suffering from reproductive problems. A total of 198 samples were collected from 165 intensive farms located in Lombardy, northern Italy.N. caninumsamples were subjected to multilocus-microsatellite genotyping using ten previously established microsatellite markers. In addition to our own data, those from a recent study providing data on five markers from other northern Italian regions were included and analysed.

Results

Of the 55 samples finally subjected to genotyping, 35 were typed at all or 9 out of 10 loci and their individual multilocus-microsatellite genotype (MLMG) determined. Linear regression revealed a statistically significant association between the spatial distance of the sampling sites with the genetic distance ofN. caninumMLMGs (P < 0.001). Including data from this and a previous North Italian study into eBURST analysis revealed that several ofN. caninumMLMGs from northern Italy separate into four groups; most of the samples from Lombardy clustered in one of these groups. Principle component analysis revealed similar clusters and confirmed MLMG groups identified by eBURST. Variations observed between MLMGs were not equally distributed over all loci, but predominantly observed in MS7, MS6A, or MS10.

Conclusions

Our findings confirm the concept of localN. caninumsubpopulations. The geographic distance of sampling was associated with the genetic distance as determined by microsatellite typing. Results suggest that multi-parental recombination inN. caninumis a rare event, but does not exclude uniparental mating. More comprehensive studies on microsatellites inN. caninumand related species likeToxoplasma gondiishould be undertaken, not only to improve genotyping capabilities, but also to understand possible functions of these regions in the genomes of these parasites.

Graphical Abstract
Overcoming bioprocess bottlenecks in the large-scale expansion of high-quality hiPSC aggregates in vertical-wheel stirred suspension bioreactors
Authors: Borys Breanna S. , Dang Tiffany , So Tania , Rohani Leili , Revay Tamas , Walsh Tylor , Thompson Madalynn , Argiropoulos Bob , Rancourt Derrick E. , Jung Sunghoon , Hashimura Yas , Lee Brian , Kallos Michael S.
Published: January 2021

Background

Human induced pluripotent stem cells (hiPSCs) hold enormous promise in accelerating breakthroughs in understanding human development, drug screening, disease modeling, and cell and gene therapies. Their potential, however, has been bottlenecked in a mostly laboratory setting due to bioprocess challenges in the scale-up of large quantities of high-quality cells for clinical and manufacturing purposes. While several studies have investigated the production of hiPSCs in bioreactors, the use of conventional horizontal-impeller, paddle, and rocking-wave mixing mechanisms have demonstrated unfavorable hydrodynamic environments for hiPSC growth and quality maintenance. This study focused on using computational fluid dynamics (CFD) modeling to aid in characterizing and optimizing the use of vertical-wheel bioreactors for hiPSC production.

Methods

The vertical-wheel bioreactor was modeled with CFD simulation software Fluent at agitation rates between 20 and 100 rpm. These models produced fluid flow patterns that mapped out a hydrodynamic environment to guide in the development of hiPSC inoculation and in-vessel aggregate dissociation protocols. The effect of single-cell inoculation on aggregate formation and growth was tested at select CFD-modeled agitation rates and feeding regimes in the vertical-wheel bioreactor. An in-vessel dissociation protocol was developed through the testing of various proteolytic enzymes and agitation exposure times.

Results

CFD modeling demonstrated the unique flow pattern and homogeneous distribution of hydrodynamic forces produced in the vertical-wheel bioreactor, making it the opportune environment for systematic bioprocess optimization of hiPSC expansion. We developed a scalable, single-cell inoculation protocol for the culture of hiPSCs as aggregates in vertical-wheel bioreactors, achieving over 30-fold expansion in 6 days without sacrificing cell quality. We have also provided the first published protocol for in-vessel hiPSC aggregate dissociation, permitting the entire bioreactor volume to be harvested into single cells for serial passaging into larger scale reactors. Importantly, the cells harvested and re-inoculated into scaled-up vertical-wheel bioreactors not only maintained consistent growth kinetics, they maintained a normal karyotype and pluripotent characterization and function.

Conclusions

Taken together, these protocols provide a feasible solution for the culture of high-quality hiPSCs at a clinical and manufacturing scale by overcoming some of the major documented bioprocess bottlenecks.
The relationship between maximal expiratory pressure values and critical outcomes in mechanically ventilated patients: a post hoc analysis of an observational study
Authors: Combret Yann , Prieur Guillaume , Hilfiker Roger , Gravier Francis-Edouard , Smondack Pauline , Contal Olivier , Lamia Bouchra , Bonnevie Tristan , Medrinal Clément
Published: January 2021

Background

Little interest has been paid to expiratory muscle strength, and the impact of expiratory muscle weakness on critical outcomes is not known. Very few studies assessed the relationship between maximal expiratory pressure (MEP) and critical outcomes. The aim of this study was to investigate the relationship between MEP and critical outcomes.

Methods

This work was a secondary analysis of a prospective, observational study of adult patients who required mechanical ventilation for ≥ 24 h in an 18-bed ICU. MEP was assessed before extubation after a successful, spontaneous breathing trial. The relationships between MEP and extubation failure, and short-term (30 days) mortality, were investigated. Univariate logistic regressions were computed to investigate the relationship between MEP values and critical outcomes. Two multivariate analyses, with and without maximal inspiratory pressure (MIP), both adjusted using principal component analysis, were undertaken. Unadjusted and adjusted ROC curves were computed to compare the respective ability of MEP, MIP and the combination of both measures to discriminate patients with and without extubation failure or premature death.

Results

One hundred and twenty-four patients were included. Median age was 66 years (IQR 18) and median mechanical ventilation duration was 7 days (IQR 6). Extubation failure rate was 15% (18/124 patients) and the rate for 30-day mortality was 11% (14/124 patient). Higher MEP values were significantly associated with a lower risk of extubation failure in the univariate analysis [OR 0.96 95% CI (0.93–0.98)], but not with short-term mortality. MEP was independently linked with extubation failure when MIP was not included in the multivariate model, but not when it was included, despite limited collinearity between these variables. This study was not able to differentiate the respective abilities of MEP, MIP, and their combination to discriminate patients with extubation failure or premature death (adjusted AUC for the combination of MEP and MIP: 0.825 and 0.650 for extubation failure and premature death, respectively).

Conclusions

MEP is related to extubation failure. But, the results did not support its use as a substitute for MIP, since the relationship between MEP and critical outcomes was no longer significant when MIP was included. The use of MIP and MEP measurements combined did not reach higher discriminative capacities for critical outcomes that MEP or MIP alone.

Trial Registration This study was retrospectively registered at https://clinicaltrials.gov/ct2/show/NCT02363231?cond=NCT02363231&draw=2&rank=1 (NCT02363231) in 13 February 2015
Depressive effectiveness of vigabatrin (γ-vinyl-GABA), an antiepileptic drug, in intermediate-conductance calcium-activated potassium channels in human glioma cells
Authors: Hung Te-Yu , Huang Huai-Ying Ingrid , Wu Sheng-Nan , Huang Chin-Wei
Published: January 2021

Background

Vigabatrin (VGB) is an approved non-traditional antiepileptic drug that has been revealed to have potential for treating brain tumors; however, its effect on ionic channels in glioma cells remains largely unclear.

Methods

With the aid of patch-clamp technology, we investigated the effects of VGB on various ionic currents in the glioblastoma multiforme cell line 13–06-MG.

Results

In cell-attached configuration, VGB concentration-dependently reduced the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels, while DCEBIO (5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) counteracted the VGB-induced inhibition of IKCa channels. However, the activity of neither large-conductance Ca2+-activated (BKCa) nor inwardly rectifying K+ (KIR) channels were affected by the presence of VGB in human 13–06-MG cells. However, in the continued presence of VGB, the addition of GAL-021 or BaCl2 effectively suppressed BKCa and KIR channels.

Conclusions

The inhibitory effect of VGB on IKCa channels demonstrated in the current study could be an important underlying mechanism of VGB-induced antineoplastic (e.g., anti-glioma) actions.
Effects of low-dose aspirin on the osseointegration process in rats
Authors: Lupepsa Ana Carolina , Vargas-Sanchez Paula , Moro Marcella Goetz , Mecca Leomar Emanuel Almeida , Claudino Marcela , Soares Priscilla Barbosa Ferreira , Fischborn Amanda Regina , Andreis Jéssica Daniela , Franco Gilson Cesar Nobre
Published: January 2021

Background

Several drugs are capable of promoting changes in bone metabolism. The aim of this study was to evaluate the effect of long-term low-dose aspirin (LDA) therapy on implant osseointegration.

Methods

Male Wistar rats were divided into 4 groups (n= 8/group) according to oral gavage solution received prior (42 days) to the implant surgery on the tibia. The control group was treated with saline solution for 7 (CG-7) and 28 (CG-28) days. The use of low-dose aspirin was performed in AG groups (6.75 mg/kg of aspirin) for 7 (AG-7) and 28 (AG-28) days. After experimental periods, histomorphometric evaluation of bone-to-implant contact (BIC) and the bone area between threads (BABT) was performed.

Results

Reduced BIC values were detected in AG-7 (62.8% ± 17.1) group compared to AG-28 (91.9% ± 5.4), CG-7 (82.7% ± 15.2), and CG-28 (89.9% ± 9.7). BABT evaluation revealed lower values in AG-7 (70.9% ± 15.2) compared to AG-28 (95.4% ± 3.7) and CG-28 (87.1% ± 10.2) groups.

Conclusions

The treatment with low doses of aspirin promoted a discrete inhibitory effect in the early stages (7 days) of repair after implant placement, specifically in the bone deposition. However, these effects were not detected in the late stages (28 days), considering BIC and BABT parameters.
Serial whole-body cryotherapy in fibromyalgia is effective and alters cytokine profiles
Authors: Klemm Philipp , Becker Johanna , Aykara Iris , Asendorf Thomas , Dischereit Gabriel , Neumann Elena , Müller-Ladner Ulf , Lange Uwe
Published: January 2021

Introduction

Whole-body cryotherapy (WBC) has shown to be beneficial in the treatment of fibromyalgia (FM). There is cumulative evidence that cytokines play a crucial role in FM. It’s unknown whether clinical effects of WBC can be demonstrated at the molecular level and how long the effects last.

Methods

We compared effects of serial WBC (6 sessions (− 130 °C in 6 weeks) in FM patients and healthy controls (HC). Primary outcome was the change in pain level (visual analogue scale 0–100 mm) after 6 sessions. Secondary outcomes were a change in disease activity (revised Fibromyalgia Impact Questionnaire) and pain after 3 sessions and 3 months after discontinued therapy and in cytokine levels (interleukin (IL-)1, IL-6, tumor necrosis factor α (TNF-α) and IL-10). The patients’ opinions on the satisfaction, effectiveness and significance of WBC were evaluated.

Results

Twenty-three FM patients and 30 HC were enrolled. WBC resulted in a significant reduction in pain and disease activity after 3 and 6 sessions. No clinical benefit could be measured 3 months after discontinued treatment. Overall, probands were satisfied with WBC and considered WBC to be important and effective. FM patients had significantly different levels of IL-1, IL-6, TNF-α and IL-10 at each reading point compared to HC. Levels of IL-1, IL-6 and IL-10 were significantly altered over time in FM patients. Compared to HC FM patients showed a significantly different response of IL1, − 6 and − 10 to WBC.

Conclusion

Serial WBC is a fast acting and effective treatment for FM. Proven effects of WBC may be explained by changes in cytokines.
Macro- and microfeatures of Early Cambrian dolomitic microbialites from Tarim Basin, China
Authors: Li Ying , Jiang Hong-Xia , Wu Ya-Sheng , Pan Wen-Qing , Zhang Bao-Shou , Sun Chong-Hao , Yang Guo
Published: January 2021

The fabrics of microbialites preserved in limestones are generally better than in dolostones. What are the fabrics of the microbialites preserved in heavily dolomitized dolostones? This paper presents an example of a strongly dolomitized Cambrian microbialite profile. The Xiaoerblak Formation (Cambrian Series 2 Stage 3 and lower Stage 4) of the Sugaitblak section in Aksu, Xinjiang Uygur Autonomous Region, China is mainly composed of microbial dolostones. Due to strong alteration by diagenesis, their features, formation and environments have not been fully understood. Here, based on detailed observation on outcrops and thin sections, we show that this formation comprises four kinds of microbialites: laminite, thrombolite, thrombolitic laminite, andRenalcisframestone, in five intervals (Interval I to Interval V). We identified three main types of microbialite fabrics, i.e., clotted fabric, laminated fabric and skeletal fabric, and established a high-resolution vertical evolution sequence of the microbialites. The clotted fabric and the laminated fabric were further divided into subtypes. We found that the original fabrics were mainly affected by dolomitization, recrystallization and dissolution, and the alteration degree of the microbialite fabric is stronger in the lower part of this formation. The laminated fabric has the strongest resistance to diagenesis, followed by the clotted fabric. Based on studies of different rock types and sedimentary structures, we concluded that the sedimentary environment of Xiaoerblak Formation consists of three settings: a) Intervals I to III formed in restricted tidal flat environments, b) Interval IV and the lower part of Interval V in restricted deep subtidal environments, and c) upper part of Interval V in shallowing-up open subtidal environments.
Can white matter lesion burden predict involvement of normal appearing thalami in multiple sclerosis? Study using 3D FLAIR and DTI
Authors: Homos Mohamed D.
Published: January 2021

Background

Multiple sclerosis is a chronic demyelinating disease that affects the white and grey matter. The thalamus is responsible for many neurological functions, and it is liable to damage in multiple sclerosis in the absence of MRI-detectable thalamic lesions. Standardized imaging protocol for multiple sclerosis includes 3D FLAIR sequence that is highly sensitive in detecting white matter lesions. Owing to the thalamic functional importance, we aim in this study to show to what extent the standardized imaging protocol (3D FLAIR) can predict microscopic damage of normal appearing thalami, depending on DTI metrics (ADC and FA) as indicators of the microscopic damage.

Results

We examined 42 multiple sclerosis patients, 16 males and 26 females, with mean age 29 ± 6 years using 3D FLAIR sequence to delineate the white matter lesions and calculate their total areas and using DTI to calculate the average ADC and FA values of the thalami. Spearman’s correlation coefficient (r) was used to correlate between the white matter lesion burden and the thalamic diffusivity (ADC and FA).

Moderate correlation was found between average ADC values of the thalami and the total white matter lesion areas (r = 0.5, p = 0.03).

Very weak correlation was found between average FA values of the thalami and the total white matter lesion areas (r = − 0.1, p = 0.6)

Conclusion

White matter lesion burden detected using the highly sensitive 3D FLAIR sequence does not always correlate with the microstructural damage in normal appearing thalami. DTI needs to be added to the examination protocol if damage of normal appearing thalami is of concern.
Self-harm and suicide in adults: will safety plans keep people safe after self-harm?
Authors: House Allan
Published: January 2021

Safety planning is recommended as a part of the response to everybody who presents after self-harm, although there is surprisingly little evidence for its effectiveness. There is potential for such plans to be experienced as unhelpful if patients are not genuinely involved in their production and if the plan does not include information about meaningful sources of support. Staff training is needed to ensure that plans are delivered in a collaborative way and self-harm services need to be improved nationally if such plans are to be effective.
Machine Learning Frameworks to Predict Neoadjuvant Chemotherapy Response in Breast Cancer Using Clinical and Pathological Features
Authors: Meti Nicholas , Saednia Khadijeh , Lagree Andrew , Tabbarah Sami , Mohebpour Majid , Kiss Alex , Lu Fang-I , Slodkowska Elzbieta , Gandhi Sonal , Jerzak Katarzyna Joanna , Fleshner Lauren , Law Ethan , Sadeghi-Naini Ali , Tran William T.
Published: January 2021

PURPOSE

Neoadjuvant chemotherapy (NAC) is used to treat locally advanced breast cancer (LABC) and high-risk early breast cancer (BC). Pathological complete response (pCR) has prognostic value depending on BC subtype. Rates of pCR, however, can be variable. Predictive modeling is desirable to help identify patients early who may have suboptimal NAC response. Here, we test and compare the predictive performances of machine learning (ML) prediction models to a standard statistical model, using clinical and pathological data.

METHODS

Clinical and pathological variables were collected in 431 patients, including tumor size, patient demographics, histological characteristics, molecular status, and staging information. A standard multivariable logistic regression (MLR) was developed and compared with five ML models: k-nearest neighbor classifier, random forest (RF) classifier, naive Bayes algorithm, support vector machine, and multilayer perceptron model. Model performances were measured using a receiver operating characteristic (ROC) analysis and statistically compared.

RESULTS

MLR predictors of NAC response included: estrogen receptor (ER) status, human epidermal growth factor-2 (HER2) status, tumor size, and Nottingham grade. The strongest MLR predictors of pCR included HER2+ versus HER2− BC (odds ratio [OR], 0.13; 95% CI, 0.07 to 0.23; P < .001) and Nottingham grade G3 versus G1-2 (G1-2: OR, 0.36; 95% CI, 0.20 to 0.65; P < .001). The area under the curve (AUC) for the MLR was AUC = 0.64. Among the various ML models, an RF classifier performed best, with an AUC = 0.88, sensitivity of 70.7%, and specificity of 84.6%, and included the following variables: menopausal status, ER status, HER2 status, Nottingham grade, tumor size, nodal status, and presence of inflammatory BC.

CONCLUSION

Modeling performances varied between standard versus ML classification methods. RF ML classifiers demonstrated the best predictive performance among all models.
College of American Pathologists Cancer Protocols: From Optimizing Cancer Patient Care to Facilitating Interoperable Reporting and Downstream Data Use
Authors: Torous Vanda F. , Simpson Ross W. , Balani Jyoti P. , Baras Alexander S. , Berman Michael A. , Birdsong George G. , Giannico Giovanna A. , Paner Gladell P. , Pettus Jason R. , Sessions Zack , Sirintrapun S. Joseph , Srigley John R. , Spencer Samantha
Published: January 2021

The College of American Pathologists Cancer Protocols have offered guidance to pathologists for standard cancer pathology reporting for more than 35 years. The adoption of computer readable versions of these protocols by electronic health record and laboratory information system (LIS) vendors has provided a mechanism for pathologists to report within their LIS workflow, in addition to enabling standardized structured data capture and reporting to downstream consumers of these data such as the cancer surveillance community. This paper reviews the history of the Cancer Protocols and electronic Cancer Checklists, outlines the current use of these critically important cancer case reporting tools, and examines future directions, including plans to help improve the integration of the Cancer Protocols into clinical, public health, research, and other workflows.
Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133)
Authors: Liu Stephen V. , Reck Martin , Mansfield Aaron S. , Mok Tony , Scherpereel Arnaud , Reinmuth Niels , Garassino Marina Chiara , De Castro Carpeno Javier , Califano Raffaele , Nishio Makoto , Orlandi Francisco , Alatorre-Alexander Jorge , Leal Ticiana , Cheng Ying , Lee Jong-Seok , Lam Sivuonthanh , McCleland Mark , Deng Yu , Phan See , Horn Leora
Published: January 2021

PURPOSE:

IMpower133 (ClinicalTrials.gov identifier: NCT02763579 ), a randomized, double-blind, phase I/III study, demonstrated that adding atezolizumab (anti-programmed death-ligand 1 [PD-L1]) to carboplatin plus etoposide (CP/ET) for first-line (1L) treatment of extensive-stage small-cell lung cancer (ES-SCLC) resulted in significant improvement in overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET. Updated OS, disease progression patterns, safety, and exploratory biomarkers (PD-L1, blood-based tumor mutational burden [bTMB]) are reported.

PATIENTS AND METHODS:

Patients with untreated ES-SCLC were randomly assigned 1:1 to receive four 21-day cycles of CP (area under the curve 5 mg per mL/min intravenously [IV], day 1) plus ET (100 mg/m2 IV, days 1-3) with atezolizumab (1,200 mg IV, day 1) or placebo, and then maintenance atezolizumab or placebo until unacceptable toxicity, disease progression, or loss of clinical benefit. Tumor specimens were collected; PD-L1 testing was not required for enrollment. The two primary end points, investigator-assessed PFS and OS, were statistically significant at the interim analysis. Updated OS and PFS and exploratory biomarker analyses were conducted.

RESULTS:

Patients received atezolizumab plus CP/ET (n = 201) or placebo plus CP/ET (n = 202). At the updated analysis, median follow-up for OS was 22.9 months; 302 deaths had occurred. Median OS was 12.3 and 10.3 months with atezolizumab plus CP/ET and placebo plus CP/ET, respectively (hazard ratio, 0.76; 95% CI, 0.60 to 0.95; descriptive P = .0154). At 18 months, 34.0% and 21.0% of patients were alive in atezolizumab plus CP/ET and placebo plus CP/ET arms, respectively. Patients derived benefit from the addition of atezolizumab, regardless of PD-L1 immunohistochemistry or bTMB status.

CONCLUSION:

Adding atezolizumab to CP/ET as 1L treatment for ES-SCLC continued to demonstrate improved OS and a tolerable safety profile at the updated analysis, confirming the regimen as a new standard of care. Exploratory analyses demonstrated treatment benefit independent of biomarker status.
Implementing Systematic Genetic Counseling and Multigene Germline Testing for Individuals With Pancreatic Cancer
Authors: Chittenden Anu , Haraldsdottir Sigurdis , Ukaegbu Chinedu , Underhill-Blazey Meghan , Gaonkar Shraddha , Uno Hajime , Brais Lauren K. , Perez Kimberly , Wolpin Brian M. , Syngal Sapna , Yurgelun Matthew B.
Published: January 2021

PURPOSE:

National guidelines recommend genetic counseling and multigene germline testing (GC/MGT) for all patients with pancreatic ductal adenocarcinoma (PDAC). This study's aim was to assess real-world effectiveness of implementing systematic GC/MGT for all patients with PDAC at a high-volume academic institution.

METHODS:

An iterative process for systematizing GC/MGT was developed in which gastrointestinal oncology providers at the Dana-Farber Cancer Institute were recommended to refer all patients with PDAC for GC/MGT (clinician-directed referral). Workflows were subsequently changed such that patients with PDAC were automatically offered GC/MGT when scheduling their initial oncology consultation (automated referral). Clinical and germline data were collected on a consecutive cohort of patients with PDAC undergoing GC/MGT during a 25-month enrollment period (19-month clinician-directed referrals; 6-month automated referrals).

RESULTS:

One thousand two hundred fourteen patients with PDAC were seen for initial oncologic evaluation, 266 (21.9%) of whom underwent GC/MGT. Compared with baseline clinician-directed referrals, implementation of automated referrals led to a significant increase in patients with PDAC undergoing GC/MGT (16.5% v 38.0%, P < .001), including those undergoing multigene germline testing (MGT) ≤ 7 days of initial oncology evaluation (14.7% v 60.3%, P < .001), with preserved pathogenic variant detection rates (10.0% v 11.2%, P = 0.84). 16 of 28 (57.1%) pathogenic variant carriers had relatives who pursued cascade germline testing, and 13 of 26 (50.0%) carriers with incurable disease received targeted therapy based on MGT results.

CONCLUSION:

Implementation of systematic GC/MGT in patients with PDAC is feasible and leads to management changes for patients with PDAC and their families. GC/MGT workflows that bypass the need for clinician referral result in superior uptake and time to testing. Further investigation is needed to identify other barriers and facilitators of universal GC/MGT.
Inequities in Diabetic Ketoacidosis Among Patients With Type 1 Diabetes and COVID-19: Data From 52 US Clinical Centers
Authors: Ebekozien Osagie , Agarwal Shivani , Noor Nudrat , Albanese-O’Neill Anastasia , Wong Jenise C , Seeherunvong Tossaporn , Sanchez Janine , DeSalvo Daniel , Lyons Sarah K , Majidi Shideh , Wood Jamie R , Acharya Runa , Aleppo Grazia , Sumpter Kathryn M , Cymbaluk Anna , Shah Nirali A , Van Name Michelle , Cruz-Aviles Lisa , Alonso Guy Todd , Gallagher Mary Pat , Sanda Srinath , Feuer Alexis Jamie , Cossen Kristina , Rioles Nicole , Jones Nana-Hawa Yayah , Kamboj Manmohan K , Hirsch Irl B
Published: January 2021

Objective

We examined whether diabetic ketoacidosis (DKA), a serious complication of type 1 diabetes (T1D) was more prevalent among Non-Hispanic (NH) Black and Hispanic patients with T1D and laboratory-confirmed coronavirus disease 2019 (COVID-19) compared with NH Whites.

Method

This is a cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 52 clinical sites in the United States, data were collected from April to August 2020. We examined the distribution of patient factors and DKA events across NH White, NH Black, and Hispanic race/ethnicity groups. Multivariable logistic regression analysis was performed to examine the odds of DKA among NH Black and Hispanic patients with T1D as compared with NH White patients, adjusting for potential confounders, such as age, sex, insurance, and last glycated hemoglobin A1c (HbA1c) level.

Results

We included 180 patients with T1D and laboratory-confirmed COVID-19 in the analysis. Forty-four percent (n = 79) were NH White, 31% (n = 55) NH Black, 26% (n = 46) Hispanic. NH Blacks and Hispanics had higher median HbA1c than Whites (%-points [IQR]: 11.7 [4.7], P < 0.001, and 9.7 [3.1] vs 8.3 [2.4], P = 0.01, respectively). We found that more NH Black and Hispanic presented with DKA compared to Whites (55% and 33% vs 13%, P < 0.001 and P = 0.008, respectively). After adjusting for potential confounders, NH Black patients continued to have greater odds of presenting with DKA compared with NH Whites (OR [95% CI]: 3.7 [1.4, 10.6]).

Conclusion

We found that among T1D patients with COVID-19 infection, NH Black patients were more likely to present in DKA compared with NH White patients. Our findings demonstrate additional risk among NH Black patients with T1D and COVID-19.
Effect of Permissive Mild Hypercapnia on Cerebral Vasoreactivity in Infants: A Randomized Controlled Crossover Trial
Authors: Schopfer Leonore , Habre Walid , Pichon Isabelle , Fodor Gergely H.
Published: January 2021

BACKGROUND:

Mechanical ventilation interferes with cerebral perfusion via changes in intrathoracic pressure and/or as a consequence of alterations in CO2. Cerebral vascular vasoreactivity is dependent on CO2, and hypocapnia can potentially lead to vasoconstriction and subsequent decrease in cerebral blood flow. Thus, we aimed at characterizing whether protective ventilation with mild permissive hypercapnia improves cerebral perfusion in infants.

METHODS:

Following ethical approval and parental consent, 19 infants were included in this crossover study and randomly assigned to 2 groups for which the initial ventilation parameters were set to achieve an end-tidal carbon dioxide (Etco
2) of 6.5 kPa (group H: mild hypercapnia, n = 8) or 5.5 kPa (group N: normocapnia, n = 11). The threshold was then reversed before going back to the initial set value of normo- or hypercapnia. At each step, hemodynamic, respiratory, and near-infrared spectroscopy (NIRS)–derived parameters, including tissue oxygenation index (TOI) and tissue hemoglobin index (THI), concentration of deoxygenated hemoglobin (HHb) and oxygenated hemoglobin (O2Hb), were collected. Concomitantly, sevoflurane maintenance concentration, ventilatory (driving pressure) and hemodynamic parameters, as mean arterial pressure (MAP), were recorded.

RESULTS:

Targeting an Etco
2 of 5.5 kPa resulted in significantly higher mean driving pressure than an Etco
2 of 6.5 kPa (P < .01) with no difference between the groups in end-tidal sevoflurane, MAP, and heart rate. A large scatter was observed in NIRS-derived parameters, with no evidence for difference in Etco
2 changes between or within groups. A mild decrease with time was observed in THI and MAP in infants randomly assigned to group N (P < .036 and P < .017, respectively). When pooling all groups together, a significant correlation was found between the changes in MAP and TOI (r = 0.481, P < .001).

CONCLUSIONS:

Allowing permissive mild hypercapnia during mechanical ventilation of infants led to lower driving pressure and comparable hemodynamic, respiratory, and cerebral oxygenation parameters than during normocapnia. Whereas a large scatter in NIRS-derived parameters was observed at all levels of Etco
2, the correlation between TOI and MAP suggests that arterial pressure is an important component of cerebral oxygenation at mild hypercapnia.
Comparative Effect of Propofol and Volatile Anesthetics on Postoperative Pulmonary Complications After Lung Resection Surgery: A Randomized Clinical Trial
Authors: Li Xue-Fei , Hu Jian-Rong , Wu Yan , Chen Ying , Zhang Meng-Qiu , Yu Hai
Published: January 2021

BACKGROUND:

The effect of general anesthetics (propofol and volatile anesthetics) on pulmonary outcome after lung resection surgery with one-lung ventilation (OLV) is yet undetermined. We evaluated the effect of intravenous anesthesia (propofol) and volatile anesthesia (sevoflurane or desflurane) regimens on postoperative pulmonary complications (PPCs) in patients undergoing lung resection surgery.

METHODS:

This prospective, randomized controlled trial enrolled 555 adult patients scheduled for lung resection surgery with OLV. Participants were randomized to 1 of 3 general anesthetic regimens (propofol, sevoflurane, or desflurane). Standard anesthesia and ventilation protocols were followed in all groups. The primary outcome was a composite of PPCs in the first 7 postoperative days. Secondary outcomes included the severity of PPCs and major postoperative complications classification. Intergroup difference in the primary outcome was assessed for significance using the Pearson χ2 test.

RESULTS:

Of 837 patients who were assessed for eligibility, 555 were randomized and 545 were analyzed. One hundred and seventy-nine patients were assigned to the propofol group, 182 in the sevoflurane group, and 184 in the desflurane group. The incidence of PPCs did not differ between the combined volatile anesthetics (sevoflurane and desflurane) group and the propofol group (21.9% vs 24.0%; odds ratio, 0.89; 95% confidence interval, 0.58-1.35; P = .570). The PPCs grade and Clavien-Dindo scores did not differ significantly across groups.

CONCLUSIONS:

In patients undergoing lung resection surgery with OLV, general anesthesia with volatile anesthetics (sevoflurane or desflurane) did not reduce PPCs compared with propofol. No difference in secondary outcomes was observed.
The Prevalence and Clinical Significance of Preoperative Thrombocytopenia in Adults Undergoing Elective Surgery: An Observational Cohort Study
Authors: Matzek Luke J. , Hanson Andrew C. , Schulte Phillip J. , Evans Kimberly D. , Kor Daryl J. , Warner Matthew A.
Published: January 2021

BACKGROUND:

Preoperative thrombocytopenia is associated with inferior outcomes in surgical patients, though concurrent anemia may obfuscate these relationships. This investigation assesses the prevalence and clinical significance of preoperative thrombocytopenia with thorough consideration of preoperative anemia status.

METHODS:

This is an observational cohort study of adults undergoing elective surgery with planned postoperative hospitalization from January 1, 2009 to May 3, 2018. Patients were designated into 4 groups: normal platelet and hemoglobin concentrations, isolated thrombocytopenia (ie, platelet count <100 × 109/L), isolated anemia (ie, hemoglobin <12 g/dL women, <13.5 g/dL men), and thrombocytopenia with anemia. Thrombocytopenia was further defined as incidental (ie, previously undiagnosed) or nonincidental. Multivariable regression analyses were utilized to assess the relationships between thrombocytopenia status and clinical outcomes, with a primary outcome of hospital length of stay.

RESULTS:

A total of 120,348 patients were included for analysis: 72.3% (95% confidence interval [CI], 72.1-72.6) normal preoperative laboratory values, 26.3% (26.1-26.6) isolated anemia, 0.80% (0.75-0.86) thrombocytopenia with anemia, and 0.52% (0.48-0.56) isolated thrombocytopenia (0.38% [0.34-0.41] nonincidental, 0.14% [0.12-0.17] incidental). Thrombocytopenia was associated with longer hospital length of stay in those with concurrent anemia (multiplicative increase of the geometric mean 1.05 [1.00, 1.09] days; P = .034) but not in those with normal preoperative hemoglobin concentrations (multiplicative increase of the geometric mean 1.02 [0.96, 1.07] days; P = .559). Thrombocytopenia was associated with increased odds for intraoperative transfusion regardless of anemia status (nonanemic: 3.39 [2.79, 4.12]; P < .001 vs anemic: 2.60 [2.24, 3.01]; P < .001). Thrombocytopenia was associated with increased rates of intensive care unit (ICU) admission in nonanemic patients (1.56 [1.18, 2.05]; P = .002) but not in those with preoperative anemia (0.93 [0.73, 1.19]; P = .578).

CONCLUSIONS:

Preoperative thrombocytopenia is associated with clinical outcomes in elective surgery, both in the presence and absence of concurrent anemia. However, isolated thrombocytopenia is rare (0.5%) and is usually identified before preoperative testing. It is unlikely that routine thrombocytopenia screening is indicated for most patients.
Translation initiation in cancer at a glance
Authors: Smith Rachael C. L. , Kanellos Georgios , Vlahov Nikola , Alexandrou Constantinos , Willis Anne E. , Knight John R. P. , Sansom Owen J.
Published: January 2021

Cell division, differentiation and function are largely dependent on accurate proteome composition and regulated gene expression. To control this, protein synthesis is an intricate process governed by upstream signalling pathways. Eukaryotic translation is a multistep process and can be separated into four distinct phases: initiation, elongation, termination and recycling of ribosomal subunits. Translation initiation, the focus of this article, is highly regulated to control the activity and/or function of eukaryotic initiation factors (eIFs) and permit recruitment of mRNAs to the ribosomes. In this Cell Science at a Glance and accompanying poster, we outline the mechanisms by which tumour cells alter the process of translation initiation and discuss how this benefits tumour formation, proliferation and metastasis.
Synthesis and Characterization of 5,5′-Bitetracene
Authors: Mamada Masashi , Goushi Kenichi , Nakamura Ryota , Kaji Hironori , Adachi Chihaya
Published: January 2021

A tetracene dimer, 5,5′-bitetracene (55BT), has successfully been synthesized for the first time and its structure was confirmed by X-ray single crystal analysis. The electrochemical and optical properties of 55BT were investigated and compared to those of tetracene. Although the photoluminescence quantum yield of 55BT was slightly higher than that of tetracene, the results of the transient absorption spectroscopy suggested triplet formation by singlet fission in solution.
Validation of a Score for the Detection of Subjects with High Risk for Severe High-Altitude Illness
Authors: RICHALET JEAN-PAUL , PILLARD FABIEN , LE MOAL DAVID , RIVIÈRE DANIEL , ORIOL PHILIPPE , POUSSEL MATHIAS , CHENUEL BRUNO , DOUTRELEAU STÉPHANE , VERGÈS SAMUEL , DEMANEZ SOPHIE , VERGNION MICHEL , BOULET JEAN-MICHEL , DOUARD HERVÉ , DUPRÉ MARYSE , MESLAND OLIVIER , REMETTER ROMAIN , LONSDORFER-WOLF EVELYNE , FREY ALAIN , VILCOQ LOUIS , NEDELEC JAFFUEL ANNE , DEBEAUMONT DAVID , DUPERREX GUY , LECOQ FRANÇOIS , HÉDON CHRISTOPHE , HAYOT MAURICE , GIARDINI GUIDO , LHUISSIER FRANÇOIS J.
Published: January 2021

Purpose

A decision tree based on a clinicophysiological score (severe high-altitude illness (SHAI) score) has been developed to detect subjects susceptible to SHAI. We aimed to validate this decision tree, to rationalize the prescription of acetazolamide (ACZ), and to specify the rule for a progressive acclimatization.

Methods

Data were obtained from 641 subjects in 15 European medical centers before and during a sojourn at high altitude. Depending on the value of the SHAI score, advice was given and ACZ was eventually prescribed. The outcome was the occurrence of SHAI at high altitude as a function of the SHAI score, ACZ prescription, and use and fulfillment of the acclimatization rule.

Results

The occurrence of SHAI was 22.6%, similar to what was observed 18 yr before (23.7%), whereas life-threatening forms of SHAI (high-altitude pulmonary and cerebral edema) were less frequent (2.6%–0.8%, P = 0.007). The negative predictive value of the decision tree based was 81%, suggesting that the procedure is efficient to detect subjects who will not suffer from SHAI, therefore limiting the use of ACZ. The maximal daily altitude gain that limits the occurrence of SHAI was established at 400 m. The occurrence of SHAI was reduced from 27% to 12% when the recommendations for ACZ use and 400-m daily altitude gain were respected (P < 0.001).

Conclusions

This multicenter study confirmed the interest of the SHAI score in predicting the individual risk for SHAI. The conditions for an optimized acclimatization (400-m rule) were also specified, and we proposed a rational decision tree for the prescription of ACZ, adapted to each individual tolerance to hypoxia.
Spontaneous Eye Blink Rate Connects Missing Link between Aerobic Fitness and Cognition
Authors: KUWAMIZU RYUTA , SUWABE KAZUYA , DAMRONGTHAI CHORPHAKA , FUKUIE TAKEMUNE , OCHI GENTA , HYODO KAZUKI , HIRAGA TAICHI , NAGANO-SAITO ATSUKO , SOYA HIDEAKI
Published: January 2021

Purpose

Higher aerobic fitness, a physiological marker of habitual physical activity, is likely to predict higher executive function based on the prefrontal cortex (PFC), according to current cross-sectional studies. The exact biological link between the brain and the brawn remains unclear, but the brain dopaminergic system, which acts as a driving force for physical activity and exercise, can be hypothesized to connect the missing link above. Recently, spontaneous eye blink rate (sEBR) was proposed and has been used as a potential, noninvasive marker of brain dopaminergic activity in the neuroscience field. To address the hypothesis above, we sought to determine whether sEBR is a mediator of the association between executive function and aerobic fitness.

Methods

Thirty-five healthy young males (18–24 yr old) had their sEBR measured while staring at a fixation cross while at rest. They underwent an aerobic fitness assessment using a graded exercise test to exhaustion and performed a color–word Stroop task as an index of executive function. Stroop task–related cortical activation in the left dorsolateral PFC (l-DLPFC) was monitored using functional near-infrared spectroscopy.

Results

Correlation analyses revealed significant correlations among higher aerobic fitness, less Stroop interference, and higher sEBR. Moreover, mediation analyses showed that sEBR significantly mediated the association between aerobic fitness and Stroop interference. In addition, higher sEBR was correlated with higher neural efficiency of the l-DLPFC (i.e., executive function was high, and the corresponding l-DLPFC activation was relatively low).

Conclusion

These results indicate that the sEBR mediates the association between aerobic fitness and executive function through prefrontal neural efficiency, which clearly supports the hypothesis that brain dopaminergic function works to connect, at least in part, the missing link between aerobic fitness and executive function.
HFE Genotype and Endurance Performance in Competitive Male Athletes
Authors: THAKKAR DRISHTI , SICOVA MARC , GUEST NANCI S. , GARCIA-BAILO BIBIANA , EL-SOHEMY AHMED
Published: January 2021

Introduction

Hereditary hemochromatosis can cause individuals to absorb too much iron from their diet. Higher tissue iron content, below the threshold of toxicity, may enhance oxygen carrying capacity and offer a competitive advantage. Single nucleotide polymorphisms (SNP) in the homeostatic iron regulator (HFE) gene have been shown to modify iron metabolism and can be used to predict an individual’s risk of hemochromatosis. Several studies have shown that HFE genotypes are associated with elite endurance athlete status; however, no studies have examined whether HFE genotypes are associated with endurance performance.

Purpose

The objectives of this study were to determine whether there was an association between HFE risk genotypes (rs1800562 and rs1799945) and endurance performance in a 10-km cycling time trial as well as maximal oxygen uptake (V˙O2peak), an indicator of aerobic capacity.

Methods

Competitive male athletes (n = 100; age = 25 ± 4 yr) completed a 10-km cycling time trial. DNA was isolated from saliva and genotyped for the rs1800562 (C282Y) and rs1799945 (H63D) SNP in HFE. Athletes were classified as low risk (n = 88) or medium/high risk (n = 11) based on their HFE genotype for both SNP using an algorithm. ANCOVA was conducted to compare outcome variables between both groups.

Results

Individuals with the medium- or high-risk genotype were ~8% (1.3 min) faster than those with the low-risk genotype (17.0 ± 0.8 vs 18.3 ± 0.3 min, P = 0.05). V˙O2peak was ~17% (7.9 mL·kg−1⋅min−1) higher in individuals with the medium- or high-risk genotype compared with those with the low-risk genotype (54.6 ± 3.2 vs 46.7 ± 1.0 mL·kg−1⋅min−1, P = 0.003).

Conclusion

Our findings show that HFE risk genotypes are associated with improved endurance performance and increased V˙O2peak in male athletes.
Contrast-enhanced ultrasound in evaluation of adrenal lesions with CT/MRI correlation
Authors: Aggarwal Ankita , Das Chandan Jyoti
Published: January 2021

Most of the adrenal masses are incidentally detected. Multiphasic CT forms the mainstay for diagnosis and characterization of adrenal masses. MRI can further be used if the masses are indeterminate on CT scan. But as these investigations are expensive with risk of radiation exposure, contrast-enhanced ultrasound (CEUS) is currently under evaluation to assess its utility to act as a screening modality to differentiate benign vs malignant adrenal masses This investigative modality is relatively safe and can be used in patients having renal dysfunction or allergy to CT contrast. We, hereby, present a pictorial review of imaging appearance of various adrenal lesions on CEUS with CT and MRI correlation.
Hemodialysis as long term treatment: Patients satisfaction and its impact on quality of life
Authors: Iqbal Muhammad Sajid , Iqbal Quratulain , Iqbal Shahreen , Ashraf Sania
Published: January 2021

Objective: To determine the level of satisfaction as hemodialysis a long term treatment and quality of life in patients off End Stage Kidney Disease ESKD on hemodialysis.

Methods: A cross-sectional study was carried out from January to April 2019 in hemodialysis unit of Lahore General Hospital on 141 ESKD patients by using self-designed questionnaire after informed consent.

Results: Majority (82.56%) of the participants were satisfied with the care provided at the dialysis center. except with the time spent with doctor and 36.9% were not satisfied with their cannulation technique for dialysis. About 89.9% were satisfied with the knowledge provided to them about self-care. Satisfaction is subjective well-being in different aspects of life, including mental health and behavior of people experiencing serious health concerns. Quality of Life (QOL) is defined as “perception of one’s position in life, in the light of his culture and customs, consisting someone’s goals, standards or expectations. Financial problems to the patient was limited to the transportation as dialysis session and erythropoietin were free, but 54.1% of the patients were unable to earn due to their disease even those who were working ,80% of them had to take the day off for dialysis. The financial burden and debilitating illness didn’t cause separation/divorce from spouse but led to increased frequency of scuffles. Among the unmarried population, 40% of it does not want to start a relationship and 40% is facing difficulties in finding a partners while 97.9% of the population is satisfied with the psychological and emotional support of family.

Conclusion: Most patients were satisfied with their decision of opting hemodialysis as treatment and care provided at dialysis centre, although Quality of Life was badly affected in terms of financial and psycho-social aspects. Employed, married with good income have good quality of life. Loopholes of unit environment and health education were also exposed. Despite the medical advancement and emerging techniques to make dialysis better, the outcome of hemodialysis has yet to reach a safe level and more work should be done to improve patient’s outcome.

doi: https://doi.org/10.12669/pjms.37.2.2747

How to cite this:Iqbal MS, Iqbal Q, Iqbal S, Ashraf S. Hemodialysis as long term treatment: Patients satisfaction and its impact on quality of life. Pak J Med Sci. 2021;37(2):398-402. doi: https://doi.org/10.12669/pjms.37.2.2747

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.