Questioning the "Ease" in disease: Was living with HIV a burden or boost during the first wave of Covid-19 in France? A qualitative study (COVIDHIV).

INTRODUCTION: Clinical research has focused on risk factors and treatment for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), particularly in people with a comorbidity including the human immunodeficiency virus (HIV), but little attention has been paid to the care pathway. This article aims to show how living with HIV may have been a biopsychosocial burden or boost in care pathways for Covid-19. METHOD: People living with HIV (PLHIV) from 9 clinical centers were invited to participate in this qualitative study. The sampling was purposive with a maximum variation in their sociodemographic profiles. Semi-structured interviews were conducted until data saturation, then coded for thematic analysis, using an inductive general approach. RESULTS: We interviewed 34 PLHIV of which 20 had SARS-COV-2 once. They were 24 males, 26 born in France; median age: 55. Twenty had a CD4 number above 500, and all were on antiretroviral therapy (ART). HIV appeared as a burden when Covid-19 symptoms reminded HIV seroconversion, fear of contamination, and triggered questions about ART effectiveness. HIV was not considered relevant when diagnosing Covid-19, caused fear of disclosure when participants sought SARS-COV-2 testing, and its care in hospitals was disrupted by the pandemic. ART-pill fatigue caused avoidance for Covid-19 treatment. As a boost, living with HIV led participants to observe symptoms, to get advice from healthcare professionals, and screening access through them. Some participants could accept the result of screening or a clinical diagnosis out of resilience. Some could consider ART or another drug prescribed by their HIV specialist help them to recover from Covid-19. CONCLUSION: Living with HIV could function as a burden and/or a boost in the care pathways for Covid-19, according to patients' relationship to their HIV history, comorbidities and representation of ART. Covid-19 in PLHIV needs further qualitative study to gain a more comprehensive assessment of the pandemic's consequences on their lives and coping strategies.

Risk of cancer in patients with sleep apnea: comparison of surgery versus CPAP in a long-term follow-up study.

PURPOSE: This study aimed to obtain a comprehensive view of the risk of developing cancer in patients with obstructive sleep apnea (OSA) and to compare this risk between patients receiving continuous positive airway pressure (CPAP) therapy versus upper airway surgery (UAS). METHODS: We used both local data and a global-scale federated data research network, TriNetX, to access electronic medical records, including those of patients diagnosed with OSA from health-care organizations (HCOs) worldwide. We used propensity score matching and the score-matched analyses of data for 5 years of follow-up, RESULTS: We found that patients who had undergone UAS had a similar risk of developing cancer than those who used CPAP [hazard ratio of 0.767 (95% CI 0.559-1.053; P = 0.100)]. CONCLUSION: Analysis of the large data sets collected from HCOs in Europe and globally lead us to conclude that in patients with OSA, neither CPAP nor UAS were associated with the development of cancer better than in non-treated patients.

Two cases of viral re-suppression after M184V + R263†K selection on DTG/3TC without treatment modification.

DTG/3TC has a high genetic barrier against the development of HIV drug resistance. We report two cases of R263K + M184 V mutations during DTG/3TC failure followed by viral suppression after adherence intervention without treatment change that we attribute to residual drug activity, reduced viral fitness, and robust immune competence.

Comparison of HIV-1 DNA load measurements in blood and in relation to successful proviral sequencing.

OBJECTIVE: HIV DNA sequencing is now routinely used for HIV-infected individuals on antiretroviral therapy (ART) with or without partial genotypic history. Successful amplification of HIV pol gene has yet to be correlated with HIV DNA levels. Here, we assessed the relationship between HIV DNA load and sequencing results. METHODS: We analyzed three different qPCR measurements of total (LTR and LTR-gag) and integrated (Alu-LTR) HIV DNA in blood samples collected from viremic as well as virally suppressed HIV-infected individuals on ART. HIV DNA levels were compared to HIV DNA Sanger sequencing and clinical and therapeutic parameters. RESULTS: Among the 135 individuals analyzed for HIV DNA measurements and sequencing, all three HIV DNA measurements were associated with HIV DNA Sanger sequencing results. A threshold of around 2 and 1.5 log copies/million leukocytes of total HIV DNA was identified for LTR and LTR-gag qPCRs, respectively. Integrated HIV DNA positivity was also associated with successful sequencing. We further compared HIV DNA measurement techniques in an extended cohort of 312 individuals and showed that all measurements correlated between the different techniques, regardless of the HIV-1 subtypes analyzed. However, higher detection rates were observed with LTR (96%) compared to LTR-gag (86%) and Alu-LTR (59%) qPCRs. Duration of virological control on ART and CD4 nadir were the main determinants of HIV reservoir size. CONCLUSIONS: HIV DNA measurement is associated with Sanger sequencing success, regardless of the technique used. In a clinical setting, Application of HIV DNA quantification before sequencing should be further evaluated.

Reply to: Letter to the Editor of Journal of Otolaryngology regarding "Risk of diabetes in patients with sleep apnea: comparison of surgery versus CPAP in a long-term follow-up study".

A recent Letter published, in the Journal of Otolaryngology-Head & Neck Surgery in response to our original article "Risk of diabetes in patients with sleep apnea: comparison of surgery versus Continous Positive Airway Pressure in a long-term follow-up study" raised some issues we would like to address here. However, we thank the authors for their effort and time in analyzing our manuscript and we want to facilitate a balanced discussion on this topic with our reply.

Impact of the ABO and RhD Blood Groups on the Evaluation of the Erythroprotective Potential of Fucoxanthin, ß-Carotene, Gallic Acid, Quercetin and Ascorbic Acid as Therapeutic Agents against Oxidative Stress.

Previous studies detail that different blood groups are associated with incidence of oxidative stress-related diseases such as certain carcinomas. Bioactive compounds represent an alternative for preventing this oxidative stress. The aim of this study was to elucidate the impact of blood groups on the erythroprotective potential of fucoxanthin, ß-Carotene, gallic acid, quercetin and ascorbic acid as therapeutic agents against oxidative stress. The impact of ABO blood groups on the erythroprotective potential was evaluated via the antioxidant capacity, blood biocompatibility, blood susceptibility and erythroprotective potential (membrane stabilization, in vitro photostability and antihemolytic activity). All tested antioxidants exhibited a high antioxidant capacity and presented the ability to inhibit ROO•-induced oxidative stress without compromising the cell membrane, providing erythroprotective effects dependent on the blood group, effects that increased in the presence of antigen A. These results are very important, since it has been documented that antigen A is associated with breast and skin cancer. These results revealed a probable relationship between different erythrocyte antigens with erythroprotective potential, highlighting the importance of bio-targeted drugs for groups most susceptible to certain chronic-degenerative pathologies. These compounds could be applied as additive, nutraceutical or encapsulated to improve their bioaccessibility.

Active and Intelligent Packaging: A Review of the Possible Application of Cyclodextrins in Food Storage and Safety Indicators.

Natural cyclodextrins (CDs) can be formed by 6, 7, or 8 glucose molecules (α-, ß-, and γ-, respectively) linked in a ring, creating a cone shape. Its interior has an affinity for hydrophobic molecules, while the exterior is hydrophilic and can interact with water molecules. This feature has been used to develop active packaging applied to food, interacting with the product or its environment to improve one or more aspects of its quality or safety. It also provides monitoring information when food is optimal for consumption, as intelligent packaging is essential for the consumer and the merchant. Therefore, this review will focus on discerning which packaging is most appropriate for each situation, solubility and toxicological considerations, characterization techniques, effect on the guest properties, and other aspects related to forming the inclusion complex with bioactive molecules applied to packaging.

Advances in robotic lung transplantation: development and validation of a new surgical technique in animal models.

The objective of this study was to describe a novel minimally invasive robotic video-assisted approach for lung transplantation, utilizing a minimally invasive technique with a subxiphoid incision, in an animal experimentation model. Two left robotic-assisted single lung transplants were performed in sheep using a robotic surgical system. A subxiphoid incision was made, and robotic ports were inserted into the thoracic cavity for dissection and anastomoses of the bronchus, artery, and pulmonary veins. The integrity of anastomoses was evaluated, and procedural details were recorded. Both animals survived the procedure, with a mean duration of 255 min and a mean console time of 201 min. Anastomoses were performed without complications, and the closed-chest approach with a subxiphoid incision proved successful in preventing gas leakage. The novel approach demonstrated improved exposure and workflow compared to existing techniques. The minimally invasive robotic video-assisted approach for lung transplantation utilizing a closed-chest technique with a subxiphoid incision appears safe and feasible in an animal experimentation model. Further studies in the clinical setting are warranted to establish its feasibility and safety in human lung transplantation. This approach has the potential to offer benefits over the traditional Clamshell incision in lung transplantation procedures.

No Association Between HLA-B*57:01 and Prevalence and/or Outcome of Progressive Multifocal Leukoencephalopathy in a French Nationwide Human Immunodeficiency Virus Cohort.

Among 34,351 patients living with human immunodeficiency virus with available HLA-B*57:01 included in the Dat'AIDS cohort, 194 patients (0.56%) had a history of progressive multifocal leukoencephalopathy (PML) and 1,746 (5.08%) were carriers of HLA-B*57:01. The frequency of HLA-B*57:01 was similar among patients with history of PML compared with patients without a history of PML (6.19% [95% confidence interval, CI 2.8%-9.6%] vs. 5.08% [95% CI 4.8%-5.3%]; p = .48). Among patients with PML, clinical and biological characteristics at PML diagnosis and the PML outcome were not different according to HLA-B*57:01 status.

Country of birth is associated with discrepancies in the prescription of two-drug regimens in successfully treated people with HIV in France.

OBJECTIVES: We aimed to examine the association of the country of birth and the other patients' characteristics with the prescription of two-drug regimens (2DRs) in virally suppressed people with HIV (PWH) in France. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who were actively in care on 31 December 2020 in 26 French centers, with an HIV plasma viral load (pVL) <50 copies/ml for at least 6 months while on antiretroviral therapy (ART). Patients with chronic hepatitis B were excluded because they are not eligible to 2DRs. Univariate and multivariate logistic regressions were built to analyze relationships between patients' characteristics and receiving a 2DR. RESULTS: We analyzed data from 28 395 PWH: 41.7% men who have sex with men, 31.7% women and 26.5% heterosexual men; 35% born abroad. Median age was 53 years [interquartile range (IQR) 44-60]; ART duration 14 years (8-23); duration of virological suppression 87 months (42-142). 2DRs (mainly dolutegravir/rilpivirine, 53.8%, or dolutegravir/lamivudine, 41.7%) were prescribed in 16.3% of the patients and were less common in the 'born abroad' group (18.9% versus 11.5%). The multivariate model showed that individuals born in France were more likely to receive a 2DR [adjusted odds ratio (aOR): 1.62 [1.50-1.74]], independently of other characteristics. Older PLWH and those with higher CD4 + T-cell counts were also more likely to receive a 2DR. CONCLUSION: Despite unrestricted access to ART in France, independently from HIV disease parameters, PWH born abroad were less likely to receive 2DRs as a maintenance regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.

A global federated real-world data and analytics platform for research.

Objective: This article describes a scalable, performant, sustainable global network of electronic health record data for biomedical and clinical research. Materials and Methods: TriNetX has created a technology platform characterized by a conservative security and governance model that facilitates collaboration and cooperation between industry participants, such as pharmaceutical companies and contract research organizations, and academic and community-based healthcare organizations (HCOs). HCOs participate on the network in return for access to a suite of analytics capabilities, large networks of de-identified data, and more sponsored trial opportunities. Industry participants provide the financial resources to support, expand, and improve the technology platform in return for access to network data, which provides increased efficiencies in clinical trial design and deployment. Results: TriNetX is a growing global network, expanding from 55 HCOs and 7 countries in 2017 to over 220 HCOs and 30 countries in 2022. Over 19 000 sponsored clinical trial opportunities have been initiated through the TriNetX network. There have been over 350 peer-reviewed scientific publications based on the network's data. Conclusions: The continued growth of the TriNetX network and its yield of clinical trial collaborations and published studies indicates that this academic-industry structure is a safe, proven, sustainable path for building and maintaining research-centric data networks.

Automatic Outlier Detection in Laboratory Result Distributions Within a Real World Data Network.

Laboratory data must be interoperable to be able to accurately compare the results of a lab test between healthcare organizations. To achieve this, terminologies like LOINC (Logical Observation Identifiers, Names and Codes) provide unique identification codes for laboratory tests. Once standardized, the numeric results of laboratory tests can be aggregated and represented in histograms. Due to the characteristics of Real World Data (RWD), outliers and abnormal values are common, but these cases should be treated as exceptions, excluding them from possible analysis. The proposed work analyses two methods capable of automating the selection of histogram limits to sanitize the generated lab test result distributions, Tukey's box-plot method and a "Distance to Density" approach, within the TriNetX Real World Data Network. The generated limits using clinical RWD are generally wider for Tukey's method and narrower for the second method, both greatly dependent on the values used for the algorithm's parameters.

Country of birth is associated with antiretroviral therapy choice in treatment-naive persons with HIV in France.

OBJECTIVES: We aimed to describe factors associated with the choice of first antiretroviral therapy (ART) in persons with HIV (PWH) in France, included the country of birth, as well as the time to undetectable viral load and treatment discontinuation. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who started their first ART between 01 January 2014 and 31 December 2020, with a pretherapeutic plasma viral load (pVL) at least 400 copies/ml. Univariable and multivariable logistic regressions were used to analyze PWH characteristics driving to an integrase strand transfer inhibitors (INSTI)-based first prescribed regimen. We also analyzed time to first line discontinuation, and to a first undetectable pVL, using Kaplan-Meier model. RESULTS: We analyzed data from 9094 PWH: 45% MSM, 27% women and 27% heterosexual men; 48% born abroad; 4.7 and 2.8% with concomitant hepatitis B and tuberculosis, respectively. INSTIs were prescribed as first-line therapy in 50% of PWH, which increased over time. Native French PWH were more likely to receive an INSTI-based regimen than PWH born abroad [adjusted prevalence ratio 1.47, 95% confidence interval (CI) 1.33-1.60], as were high pVL at diagnosis, hepatitis B or concomitant tuberculosis. Time before discontinuation of the first ART and reaching a first undetectable pVL was not different according to the place of birth. CONCLUSION: Despite unrestricted access to INSTIs in France, independently from HIV disease parameters, PWH born abroad received INSTIs less frequently as a first regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.

Adenomyosis in Pregnancy-Should It Be Managed in High-Risk Obstetric Units?

BACKGROUND: Uterine adenomyosis is an increasingly frequent disorder. Our study aimed to demonstrate the presence of obstetric complications in the population affected by this condition to demonstrate the need for follow-up in high-risk obstetric units. MATERIAL AND METHODS: The data for the study were obtained from TriNetX, LLC, between 2010 and 2020. The outcomes analyzed were intrauterine growth restriction (IUGR), preterm delivery, cesarean delivery, hypertension, abruption placentae, and spontaneous abortion. Seven thousand six hundred and eight patients were included in the cohort of pregnant patients with adenomyosis, and 566,153 women in the cohort of pregnant patients without any history of endometriosis. RESULTS: Upon calculating the total risk of presenting any of these problems during pregnancy, we obtained an OR = 1.521, implying that a pregnancy with adenomyosis was 52.1% more likely to present some complication. We found: IUGR OR = 1.257 (95% CI: 1.064-1.485) (p = 0.007); preterm delivery OR = 1.422 (95% CI: 1.264-1.600) (p = 0.0001); cesarean delivery OR = 1.099 (95% CI: 1.002-1.205) (p = 0.046); hypertensive disorders OR = 1.177 (95% CI: 1.076-1.288) (p = 0.0001); abruption placentae OR = 1.197 (95% CI: 1.008-1.422) (p = 0.040), and spontaneous abortion OR = 1.529 (95% CI: 1.360-1.718) (p = 0.0001). CONCLUSION: We conclude that the review carried out and the data we obtained on increased risk provide sufficient evidence to recommend that patients with adenomyosis should be managed in obstetric high-risk units.

Development of Silk Fibroin Scaffolds for Vascular Repair.

Silk fibroin (SF) is a biocompatible natural protein with excellent mechanical characteristics. SF-based biomaterials can be structured using a number of techniques, allowing the tuning of materials for specific biomedical applications. In this study, SF films, porous membranes, and electrospun membranes were produced using solvent-casting, salt-leaching, and electrospinning methodologies, respectively. SF-based materials were subjected to physicochemical and biological characterizations to determine their suitability for tissue regeneration applications. Mechanical analysis showed stress-strain curves of brittle materials in films and porous membranes, while electrospun membranes featured stress-strain curves typical of ductile materials. All samples showed similar chemical composition, melting transition, hydrophobic behavior, and low cytotoxicity levels, regardless of their architecture. Finally, all of the SF-based materials promote the proliferation of human umbilical vein endothelial cells (HUVECs). These findings demonstrate the different relationship between HUVEC behavior and the SF sample's topography, which can be taken advantage of for the design of vascular implants.

Risk of diabetes in patients with sleep apnea: comparison of surgery versus CPAP in a long-term follow-up study.

This study aimed to obtain a comprehensive view of the risk of developing diabetes in patients with obstructive sleep apnea (OSA) and to compare this risk between patients receiving continuous positive airway pressure (CPAP) therapy versus upper airway surgery (UAS). We used local and the global-scale federated data research network TriNetX to obtain access to electronic medical records, including those for patients diagnosed with OSA, from health-care organizations (HCOs) worldwide. Using propensity score matching and the score-matched analyses of data for 5 years of follow-up, we found that patients who had undergone UAS had a lower risk of developing diabetes than those who used CPAP (risk ratio 0.415, 95% confidence interval (CI) 0.349-0.493). The risk for newly diagnosed diabetes patients showed a similar pattern (hazard ratio 0.382; 95% CI 0.317-0.459). Both therapies seem to protect against diabetes (Risk 0.081 after UAS vs. 0.195 after CPAP). Analysis of the large data sets collected from HCOs in Europe and globally lead us to conclude that, in patients with OSA, UAS can prevent the development of diabetes better than CPAP.

HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS.

Background: Throughout HIV infection, productively infected cells generate billions of viral particles and are thus responsible for body-wide HIV dissemination, but their phenotype during AIDS is unknown. As AIDS is associated with immunological changes, analyzing the phenotype of productively infected cells can help understand HIV production during this terminal stage. Methods: Blood samples from 15 untreated viremic participants (recent infection, n=5; long-term infection, n=5; active opportunistic AIDS-defining disease, n=5) and 5 participants virologically controlled on antiretroviral therapy (ART) enrolled in the Analysis of the Persistence, Reservoir and HIV Latency (APRIL) study (NCT05752318) were analyzed. Cells expressing the capsid protein p24 (p24+ cells) after 18 hours of resting or 24 hours of stimulation (HIV-Flow) revealed productively infected cells from viremic participants or translation-competent reservoir cells from treated participants, respectively. Results: The frequency of productively infected cells tended to be higher during AIDS in comparison with recent and long-term infections (median, 340, 72, and 32/million CD4+ T cells, respectively) and correlated with the plasma viral load at all stages of infection. Altogether, these cells were more frequently CD4low, HLA-ABClow, CD45RA-, Ki67+, PD-1+, with a non-negligible contribution from pTfh (CXCR5+PD-1+) cells, and were not significantly enriched in HIV coreceptors CCR5 nor CXCR4 expression. The comparison markers expression between stages showed that productively infected cells during AIDS were enriched in memory and exhausted cells. In contrast, the frequencies of infected pTfh were lower during AIDS compared to non-AIDS stages. A UMAP analysis revealed that total CD4+ T cells were grouped in 7 clusters and that productive p24+ cells were skewed to given clusters throughout the course of infection. Overall, the preferential targets of HIV during the latest stages seemed to be more frequently highly differentiated (memory, TTD-like) and exhausted cells and less frequently pTfh-like cells. In contrast, translation-competent reservoir cells were less frequent (5/million CD4+ T cells) and expressed more frequently HLA-ABC and less frequently PD-1. Conclusions: In long-term infection and AIDS, productively infected cells were differentiated and exhausted. This could indicate that cells with these given features are responsible for HIV production and dissemination in an immune dysfunction environment occurring during the last stages of infection.

Use of Pleurotus ostreatus to Enhance the Oxidative Stability of Pork Patties during Storage and In Vitro Gastrointestinal Digestion.

Lipid and protein oxidation are the major causes of meat quality deterioration. Edible mushrooms have been proposed as a strategy to prevent quality deterioration during cold storage. This study aimed to assess the effects of Pleurotus ostreatus powder (POP) on the oxidative stability of pork patties during cold storage and after in vitro gastrointestinal digestion (ivGD). Pork patties were subjected to four treatments: control (without antioxidant), T1 (2% POP, w/w) and T2 (5% POP, w/w), and T3 as positive control (0.02% BHT, fat basis). POP aqueous, ethanolic, and aqueous ethanol extract were subjected to phytochemical and antioxidant assays. Raw pork patties were subjected to a chemical proximate composition evaluation. At the same time, raw and cooked pork patties were stored at 2 °C for 9 days and subjected to meat quality measurements. Furthermore, the total antioxidant activity of cooked pork patties was determined after ivGD. Results showed that POP ethanol extract showed the highest polysaccharide, phenol, and flavonoid content, as well as antiradical and reducing power properties. POP incorporation into raw and cooked pork patties enhances meat quality traits, including pH, water-holding capacity, cooking-loss weight, texture, color, lipid, and protein oxidation (p < 0.05). Furthermore, incorporating POP into cooked samples increases the phytochemical content and antioxidant activity during ivGD. In conclusion, POP has great potential as a natural antioxidant for meat products.

Development and evaluation of different electroactive poly(vinylidene fluoride) architectures for endothelial cell culture.

Tissue engineering (TE) aims to develop structures that improve or even replace the biological functions of tissues and organs. Mechanical properties, physical-chemical characteristics, biocompatibility, and biological performance of the materials are essential factors for their applicability in TE. Poly(vinylidene fluoride) (PVDF) is a thermoplastic polymer that exhibits good mechanical properties, high biocompatibility and excellent thermal properties. However, PVDF structuring, and the corresponding processing methods used for its preparation are known to significantly influence these characteristics. In this study, doctor blade, salt-leaching, and electrospinning processing methods were used to produce PVDF-based structures in the form of films, porous membranes, and fiber scaffolds, respectively. These PVDF scaffolds were subjected to a variety of characterizations and analyses, including physicochemical analysis, contact angle measurement, cytotoxicity assessment and cell proliferation. All prepared PVDF scaffolds are characterized by a mechanical response typical of ductile materials. PVDF films displayed mostly vibration modes for the a-phase, while the remaining PVDF samples were characterized by a higher content of electroactive ß-phase due the low temperature solvent evaporation during processing. No significant variations have been observed between the different PVDF membranes with respect to the melting transition. In addition, all analysed PVDF samples present a hydrophobic behavior. On the other hand, cytotoxicity assays confirm that cell viability is maintained independently of the architecture and processing method. Finally, all the PVDF samples promote human umbilical vein endothelial cells (HUVECs) proliferation, being higher on the PVDF film and electrospun randomly-oriented membranes. These findings demonstrated the importance of PVDF topography on HUVEC behavior, which can be used for the design of vascular implants.

Application of Recursive Estimation to Heat Tracing for Groundwater/Surface-Water Exchange.

We present and demonstrate a recursive-estimation framework to infer groundwater/surface-water exchange based on temperature time series collected at different vertical depths below the sediment/water interface. We formulate the heat-transport problem as a state-space model (SSM), in which the spatial derivatives in the convection/conduction equation are approximated using finite differences. The SSM is calibrated to estimate time-varying specific discharge using the Extended Kalman Filter (EKF) and Extended Rauch-Tung-Striebel Smoother (ERTSS). Whereas the EKF is suited to real-time ("online") applications and uses only the past and current measurements for estimation (filtering), the ERTSS is intended for near-real time or batch-processing ("offline") applications and uses a window of data for batch estimation (smoothing). The two algorithms are demonstrated with synthetic and field-experimental data and are shown to be efficient and rapid for the estimation of time-varying flux over seasonal periods; further, the recursive approaches are effective in the presence of rapidly changing flux and (or) nonperiodic thermal boundary conditions, both of which are problematic for existing approaches to heat tracing of time-varying groundwater/surface-water exchange.