Publications by authors named "Francesco d"

88 Publications

A data-driven health index for neonatal morbidities.

iScience 2022 Apr 22;25(4):104143. Epub 2022 Mar 22.

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.

Whereas prematurity is a major cause of neonatal mortality, morbidity, and lifelong impairment, the degree of prematurity is usually defined by the gestational age (GA) at delivery rather than by neonatal morbidity. Here we propose a multi-task deep neural network model that simultaneously predicts twelve neonatal morbidities, as the basis for a new data-driven approach to define prematurity. Maternal demographics, medical history, obstetrical complications, and prenatal fetal findings were obtained from linked birth certificates and maternal/infant hospitalization records for 11,594,786 livebirths in California from 1991 to 2012. Overall, our model outperformed traditional models to assess prematurity which are based on GA and/or birthweight (area under the precision-recall curve was 0.326 for our model, 0.229 for GA, and 0.156 for small for GA). These findings highlight the potential of using machine learning techniques to predict multiple prematurity phenotypes and inform clinical decisions to prevent, diagnose and treat neonatal morbidities.
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http://dx.doi.org/10.1016/j.isci.2022.104143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990172PMC
April 2022

A New Family of Renewable Thermosets: Kraft Lignin Poly-adipates.

ChemSusChem 2022 Mar 21:e202200326. Epub 2022 Mar 21.

Department of Organic Chemistry, Stockholm University, SE-106 91, Stockholm, Sweden.

Thermosetting polymeric materials have advantageous properties and are therefore used in numerous applications. In this study, it was hypothesized and ultimately shown that thermosets could be derived from comparably sustainable sub-components. A two-step procedure to produce a thermoset comprising of Kraft lignin (KL) and the cross-linker adipic acid (AdA) was developed. The cross-linking was activated by means of an acetylating agent comprising isopropenyl acetate (IPA) to form a cross-linking mixture (CLM). The cross-linking was confirmed by FTIR and solid-state NMR spectroscopy, and the esterification reactions were further studied using model compounds. When the KL lignin was mixed with the CLM, partial esterification occurred to yield a homogeneous viscous liquid that could easily be poured into a mold, as the first step in the procedure. Without any additions, the mold was heated and the material transformed into a thermoset by reaction of the two carboxylic acid-derivatives of AdA and KL in the second step.
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http://dx.doi.org/10.1002/cssc.202200326DOI Listing
March 2022

A Comparative Double Blind Study of Nasal Dressing Sponge versus Merocel as Nasal Pack after Nasal Surgery.

Iran J Otorhinolaryngol 2021 Nov;33(119):369-373

Otolaryngology Unit, Department of Biomedicine and Advanced Diagnostic-University of Palermo, Palermo, Italy.

Introduction: Nasal packing is a common procedure used to ensure haemostasis after nasal surgery.

Materials And Methods: A prospective, randomized, controlled and double-blinded study was conducted on 80 consecutive subjects to investigate whether using Nasal Dressing Sponge® (NDS) instead of simple Merocel® might improve patients' postoperative experience of nasal packing.

Results: During the stay of the tampons no differences were noticed between the two groups as regards the postoperative pain. When it comes to pain during the packing removal, patients complained of worse symptoms in the side packed with Merocel. There was no bleeding after the removal of Merocel, whereas 5,6% patients were subject to some bleeding when NDS was removed.

Conclusion: Merocel and NDS gave similar results regarding haemostatic activity. Nasal Dressing Sponge could decrease pain during the removal of the nasal pack, while it could be associated to a bigger incidence of mild bleeding after removing the pack.
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http://dx.doi.org/10.22038/IJORL.2021.49606.2649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829790PMC
November 2021

Objective Activity Parameters Track Patient-Specific Physical Recovery Trajectories After Surgery and Link With Individual Preoperative Immune States.

Ann Surg 2021 Oct 8. Epub 2021 Oct 8.

Department of Anesthesiology, Pain and Perioperative Medicine, Stanford University Department of Biomedical Data Science, Stanford University Department of Computer Science, University of North Carolina at Chapel Hill Department of Pediatrics, Stanford University Department of Pathology, Stanford University Department of Orthopedic Surgery, Stanford University.

Objective: The longitudinal assessment of physical function with high temporal resolution at a scalable and objective level in patients recovering from surgery is highly desirable to understand the biological and clinical factors that drive the clinical outcome. However, physical recovery from surgery itself remains poorly defined and the utility of wearable technologies to study recovery after surgery has not been established.

Background: Prolonged postoperative recovery is often associated with long-lasting impairment of physical, mental, and social functions. While phenotypical and clinical patient characteristics account for some variation of individual recovery trajectories, biological differences likely play a major role. Specifically, patient-specific immune states have been linked to prolonged physical impairment after surgery. However, current methods of quantifying physical recovery lack patient specificity and objectivity.

Methods: Here, a combined high-fidelity accelerometry and state-of-the-art deep immune profiling approach was studied in patients undergoing major joint replacement surgery. The aim was to determine whether objective physical parameters derived from accelerometry data can accurately track patient-specific physical recovery profiles (suggestive of a 'clock of postoperative recovery'), compare the performance of derived parameters with benchmark metrics including step count, and link individual recovery profiles with patients' preoperative immune state.

Results: The results of our models indicate that patient-specific temporal patterns of physical function can be derived with a precision superior to benchmark metrics. Notably, six distinct domains of physical function and sleep are identified to represent the objective temporal patterns: "activity capacity" and "moderate and overall activity" (declined immediately after surgery); "sleep disruption and sedentary activity" (increased after surgery); "overall sleep", "sleep onset", and "light activity" (no clear changes were observed after surgery). These patterns can be linked to individual patients' preoperative immune state using cross-validated canonical-correlation analysis. Importantly, the pSTAT3 signal activity in M-MDSCs predicted a slower recovery.

Conclusions: Accelerometry-based recovery trajectories are scalable and objective outcomes to study patient-specific factors that drive physical recovery.
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http://dx.doi.org/10.1097/SLA.0000000000005250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040386PMC
October 2021

Screening Accuracy of Mini Addenbrooke's Cognitive Examination Test for HIV-Associated Neurocognitive Disorders in People Ageing with HIV.

AIDS Behav 2022 Jan 4. Epub 2022 Jan 4.

Department of Medical Sciences, University of Torino at Infectious Diseases Unit, Amedeo Di Savoia Hospital, Torino, Italy.

Aging and increased cardiovascular risk are major drivers for HIV-associated neurocognitive disorders (HAND), for which accurate screenings are lacking. Mini-Addenbrooke's Cognitive Examination (MACE) reliably detects vascular and neurodegenerative cognitive decline among HIV-negative patients. We evaluated MACE diagnostic accuracy in detecting HAND in people living with HIV (PLWH) and we compared it with the International HIV Dementia Scale (IHDS). A single-centre double-blind study of diagnostic accuracy on adult outpatient PLWH without neurocognitive confounding was performed. MACE and IHDS were administered in 5 and 10 min by clinicians, followed by the reference standard battery (14 tests) by neuropsychologists. HAND diagnosis was based on the modified version of Frascati's criteria by Gisslén to reduce false positives. Exploratory cut-offs were evaluated for MACE. Diagnostic accuracy and clinical utility parameters were assessed. 231 patients were enrolled. 75.7% men with a median age, education, and length of infection of 54 (48-59), 10 (8-13) and 16 (5-25) years. HAND prevalence was 48.5% (38.9% asymptomatic impairment). Compared to IHDS, MACE sensitivity (89.3% vs 70.5%), specificity (94.1% vs 63.0%), correct classification rate (86.5% vs 66.7%), J index (0.83 vs 0.34), AUROC (0.97 vs 0.79), agreement with the gold standard (k 0.84 vs 0.33) and effect size in distinguishing HAND vs non-HAND (d 2.11 vs 1.15) were higher. Among PLWH aged 65 years and above (n = 37) MACE performance was consistently better than IHDS. The quick and easy-to-perform MACE could possess an accurate and useful screening performance for HAND in otherwise neurocognitively healthy cohorts of PLWH.
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http://dx.doi.org/10.1007/s10461-021-03563-8DOI Listing
January 2022

Liver transplantation for severe alcoholic hepatitis: A multicenter Italian study.

Am J Transplant 2022 Apr 8;22(4):1191-1200. Epub 2022 Jan 8.

Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.

There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013-2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65.6% male, median [IQR] age: 47 [42-56] years). Forty-five of 93 patients received corticosteroids, 52 of 93 were non-responders and among these, 20 patients were waitlisted. Sixteen patients underwent LT. Overall, 6-, 12-, and 24-month survival rates were 100% significantly higher compared with non-responders to medical therapy who were denied LT (45%, 45%, and 36%; p < .001). 2/16 patients resumed alcohol intake, one at 164 days and one at 184 days. Early LT significantly improves survival in sAH non-responding to medical therapy, when a strict selection process is applied. Further studies are needed to properly assess alcohol relapse rates.
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http://dx.doi.org/10.1111/ajt.16936DOI Listing
April 2022

Paracrine Shear-Stress-Dependent Signaling from Endothelial Cells Affects Downstream Endothelial Function and Inflammation.

Int J Mol Sci 2021 Dec 10;22(24). Epub 2021 Dec 10.

Laboratory of Human Anatomy, Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy.

Cardiovascular diseases (CVDs), mainly ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and major contributors to disability worldwide. Despite their heterogeneity, almost all CVDs share a common feature: the endothelial dysfunction. This is defined as a loss of functionality in terms of anti-inflammatory, anti-thrombotic and vasodilatory abilities of endothelial cells (ECs). Endothelial function is greatly ensured by the mechanotransduction of shear forces, namely, endothelial wall shear stress (WSS). Low WSS is associated with endothelial dysfunction, representing the primary cause of atherosclerotic plaque formation and an important factor in plaque progression and remodeling. In this work, the role of factors released by ECs subjected to different magnitudes of shear stress driving the functionality of downstream endothelium has been evaluated. By means of a microfluidic system, HUVEC monolayers have been subjected to shear stress and the conditioned media collected to be used for the subsequent static culture. The results demonstrate that conditioned media retrieved from low shear stress experimental conditions (LSS-CM) induce the downregulation of endothelial nitric oxide synthase (eNOS) expression while upregulating peripheral blood mononuclear cell (PBMC) adhesion by means of higher levels of adhesion molecules such as E-selectin and ICAM-1. Moreover, LSS-CM demonstrated a significant angiogenic ability comparable to the inflammatory control media (TNFα-CM); thus, it is likely related to tissue suffering. We can therefore suggest that ECs stimulated at low shear stress (LSS) magnitudes are possibly involved in the paracrine induction of peripheral endothelial dysfunction, opening interesting insights into the pathogenetic mechanisms of coronary microvascular dysfunction.
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http://dx.doi.org/10.3390/ijms222413300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709076PMC
December 2021

Clinical response to nivolumab in an INI1-deficient pediatric chordoma correlates with immunogenic recognition of brachyury.

NPJ Precis Oncol 2021 Dec 20;5(1):103. Epub 2021 Dec 20.

Canada's Michael Smith Genome Sciences Centre at BC Cancer, Vancouver, BC, Canada.

Poorly differentiated chordoma (PDC) is a recently recognized subtype of chordoma characterized by expression of the embryonic transcription factor, brachyury, and loss of INI1. PDC primarily affects children and is associated with a poor prognosis and limited treatment options. Here we describe the molecular and immune tumour microenvironment profiles of two paediatric PDCs produced using whole-genome, transcriptome and whole-genome bisulfite sequencing (WGBS) and multiplex immunohistochemistry. Our analyses revealed the presence of tumour-associated immune cells, including CD8+ T cells, and expression of the immune checkpoint protein, PD-L1, in both patient samples. Molecular profiling provided the rationale for immune checkpoint inhibitor (ICI) therapy, which resulted in a clinical and radiographic response. A dominant T cell receptor (TCR) clone specific for a brachyury peptide-MHC complex was identified from bulk RNA sequencing, suggesting that targeting of the brachyury tumour antigen by tumour-associated T cells may underlie this clinical response to ICI. Correlative analysis with rhabdoid tumours, another INI1-deficient paediatric malignancy, suggests that a subset of tumours may share common immune phenotypes, indicating the potential for a therapeutically targetable subgroup of challenging paediatric cancers.
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http://dx.doi.org/10.1038/s41698-021-00238-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688516PMC
December 2021

Correlation between cerebrospinal fluid and plasma neurofilament light protein in treated HIV infection: results from the COBRA study.

J Neurovirol 2022 Feb 7;28(1):54-63. Epub 2021 Dec 7.

Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK.

Cerebrospinal fluid (CSF) neurofilament light protein (NfL) is a marker of central nervous system neuro-axonal injury. A novel, ultra-sensitive assay can determine plasma NfL. In untreated people-with-HIV (PWH), CSF and plasma NfL are strongly correlated. We aimed to assess this correlation in PWH on suppressive antiretroviral treatment (ART) and lifestyle-similar HIV-negative individuals enrolled into the COmorBidity in Relation to AIDS (COBRA) study. Differences in paired CSF (sandwich ELISA, UmanDiagnostics) and plasma (Simoa digital immunoassay, Quanterix™) NfL between PWH and HIV-negative participants were tested using Wilcoxon's test; associations were assessed using Pearson's correlation. CSF and plasma NfL, standardised to Z-scores, were included as dependent variables in linear regression models to identify factors independently associated with values in PWH and HIV-negative participants. Overall, 132 PWH (all with plasma HIV RNA < 50 copies/mL) and 79 HIV-negative participants were included. Neither CSF (median 570 vs 568 pg/mL, p = 0.37) nor plasma (median 10.7 vs 9.9 pg/mL, p = 0.15) NfL differed significantly between PWH and HIV-negative participants, respectively. CSF and plasma NfL correlated moderately, with no significant difference by HIV status (PWH: rho = 0.52; HIV-negative participants: rho = 0.47, p (interaction) = 0.63). In multivariable regression analysis, higher CSF NfL Z-score was statistically significantly associated with older age and higher CSF protein, and higher plasma NfL Z-score with older age, higher serum creatinine and lower bodyweight. In conclusion, in PWH on ART, the correlation between CSF and plasma NfL is moderate and similar to that observed in lifestyle-similar HIV-negative individuals. Consideration of renal function and bodyweight may be required when utilising plasma NfL.
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http://dx.doi.org/10.1007/s13365-021-01026-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076742PMC
February 2022

The Role of a Navigational Radiofrequency Ablation Device and Concurrent Vertebral Augmentation for Treatment of Difficult-to-Reach Spinal Metastases.

Curr Oncol 2021 10 8;28(5):4004-4015. Epub 2021 Oct 8.

Unit of General Surgery, Department of Clinical and Experimental Medicine, University of Sassari, 07100 Sassari, Italy.

Aims: The purpose of this study was to assess the effectiveness of a navigational radiofrequency ablation device with concurrent vertebral augmentation in the treatment of posterior vertebral body metastatic lesions, which are technically difficult to access. Primary outcomes of the study were evaluation of pain palliation and radiologic assessment of local tumor control.

Materials And Methods: Thirty-five patients with 41 vertebral spinal metastases involving the posterior vertebral body underwent computed tomography-guided percutaneous targeted radiofrequency ablation, with a navigational radiofrequency ablation device, associated with vertebral augmentation. Twenty-one patients (60%) had 1 or 2 metastatic lesions (Group A) and fourteen (40%) patients had multiple (>2) vertebral lesions (Group B). Changes in pain severity were evaluated by visual analog scale (VAS). Metastatic lesions were evaluated in terms of radiological local control.

Results: The procedure was technically successful in all the treated vertebrae. Among the symptomatic patients, the mean VAS score dropped from 5.7 (95% CI 4.9-6.5) before tRFA and to 0.9 (95% CI 0.4-1.3) after tRFA ( < 0.001). The mean decrease in VAS score between baseline and one week follow up was 4.8 (95% CI 4.2-5.4). VAS decrease over time between one week and one year following radiofrequency ablation was similar, suggesting that pain relief was immediate and durable. Neither patients with 1-2 vertebral metastases, nor those with multiple lesions, showed radiological signs of local progression or recurrence of the tumor in the index vertebrae during a median follow up of 19 months (4-46 months) and 10 months (4-37 months), respectively.

Conclusion: Treatment of spinal metastases with a navigational radiofrequency ablation device and vertebral augmentation can be used to obtain local tumor control with immediate and durable pain relief, providing effective treatment in the multimodality management of difficult-to-reach spinal metastases.
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http://dx.doi.org/10.3390/curroncol28050340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534768PMC
October 2021

Myogenic Potential of Extracellular Matrix Derived from Decellularized Bovine Pericardium.

Int J Mol Sci 2021 Aug 30;22(17). Epub 2021 Aug 30.

Department of Health Sciences, University of Piemonte Orientale "A. Avogadro", 28100 Novara, Italy.

Skeletal muscles represent 40% of body mass and its native regenerative capacity can be permanently lost after a traumatic injury, congenital diseases, or tumor ablation. The absence of physiological regeneration can hinder muscle repair preventing normal muscle tissue functions. To date, tissue engineering (TE) represents one promising option for treating muscle injuries and wasting. In particular, hydrogels derived from the decellularized extracellular matrix (dECM) are widely investigated in tissue engineering applications thanks to their essential role in guiding muscle regeneration. In this work, the myogenic potential of dECM substrate, obtained from decellularized bovine pericardium (Tissuegraft Srl), was evaluated in vitro using C2C12 murine muscle cells. To assess myotubes formation, the width, length, and fusion indexes were measured during the differentiation time course. Additionally, the ability of dECM to support myogenesis was assessed by measuring the expression of specific myogenic markers: α-smooth muscle actin (α-sma), myogenin, and myosin heavy chain (MHC). The results obtained suggest that the dECM niche was able to support and enhance the myogenic potential of C2C12 cells in comparison of those grown on a plastic standard surface. Thus, the use of extracellular matrix proteins, as biomaterial supports, could represent a promising therapeutic strategy for skeletal muscle tissue engineering.
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http://dx.doi.org/10.3390/ijms22179406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431302PMC
August 2021

Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels compared to protease inhibitor-based therapy.

Elife 2021 08 13;10. Epub 2021 Aug 13.

Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam, Netherlands.

Background: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).

Methods: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4 count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART.

Results: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (p = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (p = 0.048 and p = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals.

Conclusions: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size.

Funding: This work was supported by ZonMw (09120011910035) and FP7 Health (305522).
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http://dx.doi.org/10.7554/eLife.68174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460250PMC
August 2021

Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV.

PLoS One 2021 21;16(7):e0253861. Epub 2021 Jul 21.

Department of Infectious Disease, Imperial College London, London, United Kingdom.

Objectives: To investigate the associations of plasma lamivudine (3TC), abacavir (ABC), emtricitabine (FTC) and tenofovir (TFV) concentrations with cognitive function in a cohort of treated people with HIV (PWH).

Methods: Pharmacokinetics (PK) and cognitive function (Cogstate, six domains) data were obtained from PWH recruited in the POPPY study on either 3TC/ABC or FTC/tenofovir disoproxil fumarate (TDF)-containing regimens. Association between PK parameters (AUC0-24: area under the concentration-time curve over 24 hours, Cmax: maximum concentration and Ctrough: trough concentration) and cognitive scores (standardized into z-scores) were evaluated using rank regression adjusting for potential confounders.

Results: Median (IQR) global cognitive z-scores in the 83 PWH on 3TC/ABC and 471 PWH on FTC/TDF were 0.14 (-0.27, 0.38) and 0.09 (-0.28, 0.42), respectively. Higher 3TC AUC0-24 and Ctrough were associated with better global z-scores [rho = 0.29 (p = 0.02) and 0.27 (p = 0.04), respectively], whereas higher 3TC Cmax was associated with poorer z-scores [rho = -0.31 (p<0.01)], independently of ABC concentrations. Associations of ABC PK parameters with global and domain z-scores were non-significant after adjustment for confounders and 3TC concentrations (all p's>0.05). None of the FTC and TFV PK parameters were associated with global or domain cognitive scores.

Conclusions: Whilst we found no evidence of either detrimental or beneficial effects of ABC, FTC and TFV plasma exposure on cognitive function of PWH, higher plasma 3TC exposures were generally associated with better cognitive performance although higher peak concentrations were associated with poorer performance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253861PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294567PMC
November 2021

Correlation between CSF and blood neurofilament light chain protein: a systematic review and meta-analysis.

BMJ Neurol Open 2021 16;3(1):e000143. Epub 2021 Jun 16.

Department of Infectious Disease, Imperial College London, London, UK.

Objective: To assess the overall pooled correlation coefficient estimate between cerebrospinal fluid (CSF) and blood neurofilament light (NfL) protein.

Methods: We searched Medline, Embase and Web of Science for published articles, from their inception to 9 July 2019, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies reporting the correlation between CSF and blood NfL in humans were included. We conducted a random-effects meta-analysis to calculate the overall pooled correlation coefficient estimate, accounting for correlation technique and assay used. Heterogeneity was assessed using the I statistic test. In sensitivity analyses, we calculated the pooled correlation coefficient estimate according to blood NfL assay: single-molecule array digital immunoassay (Simoa), electrochemiluminescence (ECL) assay or ELISA.

Results: Data were extracted from 36 articles, including 3961 paired CSF and blood NfL samples. Overall, 26/36 studies measured blood NfL using Simoa, 8/36 ECL, 1/36 ELISA and 1 study reported all three assay results. The overall meta-analysis demonstrated that the pooled correlation coefficient estimate for CSF and blood NfL was r=0.72. Heterogeneity was significant: I=83%, p<0.01. In sensitivity analyses, the pooled correlation coefficient was similar for studies measuring blood NfL using Simoa and ECL (r=0.69 and r=0.68, respectively) but weaker for ELISA (r=0.35).

Conclusion: Moderate correlations are demonstrated between CSF and blood NfL, especially when blood NfL was measured using Simoa and ECL. Given its high analytical sensitivity, Simoa is the preferred assay for measuring NfL, especially at low or physiological concentrations, and this meta-analysis supports its use as the current most advanced surrogate measure of CSF NfL.

Prospero Registration Number: CRD42019140469.
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http://dx.doi.org/10.1136/bmjno-2021-000143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211066PMC
June 2021

Thermal and Mechanical Properties of Esterified Lignin in Various Polymer Blends.

Molecules 2021 May 27;26(11). Epub 2021 May 27.

RenFuel K2B Materials AB, Rapsgatan 25, 754 50 Uppsala, Sweden.

Lignin is an abundant polymeric renewable material and thus a promising candidate for incorporation in various commercial thermoplastic polymers. One challenge is to increase the dispersibility of amphiphilic lignin in lipophilic thermoplastic polymers We altered Kraft lignin using widely available and renewable fatty acids, such as oleic acid, yielding more than 8 kg of lignin ester as a light brown powder. SEC showed a molecular weight of 5.8 kDa with a PDI = 3.80, while the T of the lignin ester was concluded to 70 °C. Furthermore, the lignin ester was incorporated (20%) into PLA, HDPE, and PP to establish the thermal and mechanical behavior of the blends. DSC and rheological measurements suggest that the lignin ester blends consist of a phase-separated system. The results demonstrate how esterification of lignin allows dispersion in all the evaluated thermoplastic polymers maintaining, to a large extent, the tensile properties of the original material. The impact strength of HDPE and PLA blends show substantial loss upon the addition of the lignin ester. Reconverting the acetic acid side stream into acetic anhydride and reusing the catalyst, the presented methodology can be scaled up to produce a lignin-based substitute to fossil materials.
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http://dx.doi.org/10.3390/molecules26113219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198513PMC
May 2021

Pegylated liposomal doxorubicin as first line treatment in aids-related Kaposi's sarcoma: a real-life study.

J Chemother 2021 Sep 1;33(5):342-347. Epub 2021 Jun 1.

Department of Oncology, Luigi Sacco Hospital, ASST Fatebenefratelli Sacco, Milano, Italy.

Despite the introduction of effective combination antiretroviral therapy (cART) AIDS-related Kaposi Sarcoma (AIDS-KS) remains the most common malignancy in HIV positive patients. In advanced stage or progressive forms, chemotherapy (CT) in combination with cART is the treatment of choice. The aim of the study is to evaluate efficacy and tolerability of Pegylated Liposomal Doxorubicin (PLD) as first line CT in AIDS-KS. In this single institution retrospective study PLD (20 mg/m2 IV every 2 weeks for 6 or 12 cycles) in combination with cART was administered in poor risk and some cases of good prognosis or limited cutaneous disease. Response rate and adverse events to treatment was evaluated. We enrolled 33 patients with AIDS-KS: median age 44ys, male 90.9%, Caucasian 72.7%, cART-naïve (simultaneous diagnosis of HIV infection and KS) 84.4%, median lymphocyte CD4+ count 134cells, median HIV viral load 4.9 log10 copies/ml. 32 patients were assigned to a Poor Risk KS stage. Grade 3-4 toxicity was reported in 9 patients. No cardiovascular events or severe sepsis were described. Complete response was reported in 25 of 31 patients evaluable for efficacy. After a median follow-up of 52 months the 3-years PFS was 68.6%. PLD associated with cART is an effective, feasible and well tolerated first-line CT in advanced AIDS-KS.
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http://dx.doi.org/10.1080/1120009X.2021.1920248DOI Listing
September 2021

Debottlenecking a Pulp Mill by Producing Biofuels from Black Liquor in Three Steps.

ChemSusChem 2021 Jun 6;14(11):2414-2425. Epub 2021 May 6.

Department of Organic Chemistry, Stockholm University, 10691, Stockholm, Sweden.

By extracting lignin, pulp production can be increased without heavy investments in a new recovery boiler, the typical bottleneck of a pulp mill. The extraction is performed by using 0.20 and 0.15 weight equivalents of CO and H SO respectively. Herein, we describe lignin esterification with fatty acids using benign reagents to generate a lignin ester mixable with gas oils. The esterification is accomplished by activating the fatty acid and lignin with acetic anhydride which can be regenerated from the acetic acid recycled in this reaction. The resulting mass balance ratio is fatty acid/lignin/acetic acid (2 : 1 : 0.1). This lignin ester can be hydroprocessed to generate hydrocarbons in gasoline, aviation, and diesel range. A 300-hour continuous production of fuel was accomplished. By recirculating reagents from both the esterification step and applying a water gas shift reaction on off-gases from the hydroprocessing, a favorable overall mass balance is realized.
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http://dx.doi.org/10.1002/cssc.202100496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251813PMC
June 2021

Agreement between self-reported and objective measures of sleep in people with HIV and lifestyle-similar HIV-negative individuals.

AIDS 2021 06;35(7):1051-1060

Minneapolis Veterans Affairs Healthcare System.

Objectives: The aim of this study was to evaluate the agreement between self-reported sleep measures and insomnia with objectively measured sleep parameters in people with HIV (PWH) and HIV-negative individuals.

Design: A cross-sectional analysis of PWH and lifestyle-similar HIV-negative individuals.

Methods: Self-reported measures included time spent in bed, sleep onset latency and a validated insomnia questionnaire. Objective measures were assessed via 7-days/nights of actigraphy data to determine average and intra-individual variability of several sleep measures (including time spent in bed and onset latency). Spearman's correlation coefficient and Cohen's κ were used to assess the agreement between self-reported and actigraphy-assessed measures. Associations between insomnia and actigraphy-assessed sleep parameters were evaluated using partial least-square discriminant analysis (PLS-DA).

Results: We found fair correlation between self-reported and actigraphy-assessed time spent in bed in 342 PWH (rs = 0.46) and 119 HIV-negative individuals (rs = 0.48). Among PWH, the correlation did not differ by age, education, depressive symptoms and self-reported insomnia (all P > 0.05), but was stronger in men (P = 0.05) and in those with a BMI of at least 25 kg/m2 (P < 0.001). Agreement between self-reported and actigraphy-assessed sleep onset latency was poor in both PWH (κ = 0.002, P = 0.49) and HIV-negative individuals (κ = 0.009, P = 0.65). According to PLS-DA, self-reported insomnia most strongly correlated with intra-individual variability of sleep duration, movement index and efficiency.

Conclusion: We report poor-to-fair agreement between self-reported and actigraphy-assessed sleep measures in PWH. Insomnia symptoms correlated with regularity of sleep duration, quality and efficiency. These findings highlight the importance of both patient-reported and objective measures of daily sleep variation, for better understanding sleep disorders in PWH.
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http://dx.doi.org/10.1097/QAD.0000000000002852DOI Listing
June 2021

Sleep health and cognitive function among people with and without HIV: the use of different machine learning approaches.

Sleep 2021 08;44(8)

Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA.

Study Objectives: We investigated associations between actigraphy-assessed sleep measures and cognitive function in people with and without HIV using different analytical approaches to better understand these associations and highlight differences in results obtained by these approaches.

Methods: Cognitive and 7-day/night actigraphy data were collected from people with HIV (PWH) and lifestyle-similar HIV-negative individuals from HIV and sexual health clinics in the United Kingdom/Ireland. A global cognitive T-score was obtained averaging the standardized individual cognitive test scores accounting for sociodemographics. Average and SD of 11 sleep measures over 7 days/nights were obtained. Rank regression, partial least-squares (PLS) regression, random forest, sleep dimension construct, and latent class analysis (LCA) were applied to evaluate associations between global T-scores and sleep measures.

Results: In 344 PWH (median age 57 years, 86% males), average sleep duration, efficiency, and wake after sleep onset were not associated with global T-scores according to rank regression (p = 0.51, p = 0.09, p = 0.16, respectively). In contrast, global T-scores were associated with average and SD of length of nocturnal awakenings, SD of maintenance efficiency, and average out-of-bed time when analyzed by PLS regression and random forest. No associations were found when using sleep dimensions or LCA. Overall, findings observed in PWH were similar to those seen in HIV-negative individuals (median age 61 years, 67% males).

Conclusions: Using multivariable analytical approaches, measures of sleep continuity, timing, and regularity were associated with cognitive performance in PWH, supporting the utility of newer methods of incorporating multiple standard and novel measures of sleep-wake patterns in the assessment of health and functioning.
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http://dx.doi.org/10.1093/sleep/zsab035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361343PMC
August 2021

Sleep Disorders in Human Immunodeficiency Virus: A Substudy of the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Study.

Open Forum Infect Dis 2021 Jan 18;8(1):ofaa561. Epub 2020 Nov 18.

Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA).

Methods: Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires.

Results: We enrolled 357 PWH (246 >50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls >50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2-12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia.

Conclusions: Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population.
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http://dx.doi.org/10.1093/ofid/ofaa561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781463PMC
January 2021

Correlation between computerised and standard cognitive testing in people with HIV and HIV-negative individuals.

AIDS Care 2021 10 28;33(10):1296-1307. Epub 2020 Dec 28.

Division of Infectious Diseases, Imperial College London, London, UK.

We investigated the correlations and agreement between cognitive assessments made using a computerised (CogState™, six domains) and a standard pen-and-paper battery (five domains) in PWH and lifestyle-similar HIV-negative individuals. Demographically adjusted domain and global -scores were obtained and used to define cognitive impairment according to the multivariate normative comparison (MNC) criteria. Correlations between -scores and the agreement between the classifications of cognitive impairment obtained from the two batteries were assessed using the Spearman's rank correlation and Cohen's , respectively. The correlation between global -scores from the two batteries was 0.52 (95% CI 0.44-0.60) in PWH and 0.45 (0.29-0.59) in controls (=0.38 for their difference). Correlations were generally stronger between domains within the same battery than between those from different batteries. The agreement between the two batteries in classifying individuals as cognitively impaired or not impaired was fair in PWH (=0.24) and poor in HIV-negative individuals (=-0.02). The moderate correlation between overall cognitive function and the modest agreement between binary classifications of cognitive impairment obtained from two different batteries indicate the two batteries may assess slightly different components of cognition.
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http://dx.doi.org/10.1080/09540121.2020.1865518DOI Listing
October 2021

Hippocampal-sparing radiotherapy and neurocognitive impairment: A systematic literature review.

J Cancer Res Ther 2020 Oct-Dec;16(6):1215-1222

Department of Experimental, Radiation Oncology Center, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy.

Introduction: Whole-brain radiation therapy (WBRT) is an effective therapeutic modality in patients with brain metastases. However, nearly 90% of patients undergoing WBRT suffer from a neurocognitive function (NCF) impairment at diagnosis, and up to two-thirds will experience a further decline within 2-6 months after WBRT. Focal-dose reduction on bilateral hippocampus is thought to improve NCF preservation. The aim was to present a systematic review of clinical results on NCF after hippocampal-sparing (HS) WBRT.

Materials And Methods: A systematic review of published literature was performed on PubMed and the Cochrane Library. Only prospective clinical trials reporting NCF outcome in patients treated with HS-WBRT have been analyzed.

Results: A total of 165 patients from three studies were included. These studies are characterized by small sample size and different methods in terms of WBRT technique but with similar planning analysis and NCF assessment tests. No significant changes in NCF (i.e., verbal and nonverbal learning memory, executive functions, and psychomotor speed) between baseline and 4-month follow-up after RT and only a mean relative decline in delayed recall at 4 months (7% compared to 30% of historical control) were observed.

Conclusions: Considering preliminary results on NCF preservation, further studies seem justified in patients undergoing brain irradiation for brain metastases or referred for prophylactic cranial irradiation to evaluate long-term effects on NCF and quality of life.
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http://dx.doi.org/10.4103/jcrt.JCRT_573_17DOI Listing
February 2021

Monocyte and T Cell Immune Phenotypic Profiles Associated With Age Advancement Differ Between People With HIV, Lifestyle-Comparable Controls and Blood Donors.

Front Immunol 2020 6;11:581616. Epub 2020 Oct 6.

Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.

Motivation: People with HIV on successful antiretroviral therapy show signs of premature aging and are reported to have higher rates of age-associated comorbidities. HIV-associated immune dysfunction and inflammation have been suggested to contribute to this age advancement and increased risk of comorbidities.

Method: Partial least squares regression (PLSR) was used to explore associations between biological age advancement and immunological changes in the T cell and monocyte compartment in people with HIV (n=40), comparable HIV-negative individuals (n=40) participating in the Comorbidity in Relation to AIDS (COBRA) cohort, and blood donors (n=35).

Results: We observed that age advancement in all three groups combined was associated with a monocyte immune phenotypic profile related to inflammation and a T cell immune phenotypic associated with immune senescence and chronic antigen exposure. Interestingly, a unique monocyte and T cell immune phenotypic profile predictive for age advancement was found within each group. An inflammatory monocyte immune phenotypic profile associated with age advancement in HIV-negative individuals, while the monocyte profile in blood donors and people with HIV was more reflective of loss of function. The T cell immune phenotypic profile in blood donors was related to loss of T cell function, whereas the same set of markers were related to chronic antigen stimulation and immune senescence in HIV-negative individuals. In people with HIV, age advancement was related to changes in the CD4 T cell compartment and more reflective of immune recovery after cART treatment.

Impact: The identified monocyte and T cell immune phenotypic profiles that were associated with age advancement, were strongly related to inflammation, chronic antigen exposure and immune senescence. While the monocyte and T cell immune phenotypic profile within the HIV-negative individuals reflected those observed in the combined three groups, a distinct profile related to immune dysfunction, was observed within blood donors and people with HIV. These data suggest that varying exposures to lifestyle and infection-related factors may be associated with specific changes in the innate and adaptive immune system, that all contribute to age advancement.
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http://dx.doi.org/10.3389/fimmu.2020.581616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573236PMC
June 2021

Angiogenic Potential in Biological Hydrogels.

Biomedicines 2020 Oct 20;8(10). Epub 2020 Oct 20.

Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy.

Hydrogels are three-dimensional (3D) materials able to absorb and retain water in large amounts while maintaining their structural stability. Due to their considerable biocompatibility and similarity with the body's tissues, hydrogels are one of the most promising groups of biomaterials. The main application of these hydrogels is in regenerative medicine, in which they allow the formation of an environment suitable for cell differentiation and growth. Deriving from these hydrogels, it is, therefore, possible to obtain bioactive materials that can regenerate tissues. Because vessels guarantee the right amount of oxygen and nutrients but also assure the elimination of waste products, angiogenesis is one of the processes at the base of the regeneration of a tissue. On the other hand, it is a very complex mechanism and the parameters to consider are several. Indeed, the factors and the cells involved in this process are numerous and, for this reason, it has been a challenge to recreate a biomaterial able to adequately sustain the angiogenic process. However, in this review the focal point is the application of natural hydrogels in angiogenesis enhancing and their potential to guide this process.
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http://dx.doi.org/10.3390/biomedicines8100436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589931PMC
October 2020

Synaptic impairment: The new battlefield of Alzheimer's disease.

Alzheimers Dement 2021 02 18;17(2):314-315. Epub 2020 Sep 18.

Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.

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http://dx.doi.org/10.1002/alz.12189DOI Listing
February 2021

Exercise-mediated downregulation of MALAT1 expression and implications in primary and secondary cancer prevention.

Free Radic Biol Med 2020 11 5;160:28-39. Epub 2020 Aug 5.

Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis 15, 00135, Rome, Italy. Electronic address:

Long non-coding RNAs (lncRNAs) play critical roles in various biological functions and disease processes including cancer. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was initially identified as a lncRNA with elevated expression in primary human non-small cell lung tumors with high propensity to metastasize, and subsequently shown to be highly expressed in numerous other human cancers including breast, ovarian, prostate, cervical, endometrial, gastric, pancreatic, sarcoma, colorectal, bladder, brain, multiple myeloma, and lymphoma. MALAT1 is deeply involved in several physiological processes, including alternative splicing, epigenetic modification of gene expression, cellular senescence, healthy aging, and redox homeostasis. The aim of this work was to investigate the modulation exerted by a single bout of endurance exercise on the level of MALAT1 expression in peripheral blood mononuclear cells (PBMCs) from healthy male donors displaying different training status and redox homeostasis features. Our findings show that MALAT1 is downregulated after acute endurance exercise in subjects whose fitness level guarantee a high expression of SOD1 and SOD2 antioxidant genes and low levels of endogenous oxidative damage. In vitro protocols in Jurkat lymphoblastoid cells exposed to pro-oxidant environment confirmed the link between MALAT1 expression and antioxidant gene modulation, documenting p53 phosphorylation and its recruitment to MALAT1 promoter. Remarkably, analyses of Microarray-Based Gene Expression Profiling revealed high MALAT1 expression in leukemia patients in comparison to healthy control and a significant negative correlation between MALAT1 and SOD1 expression. Collectively our results highlight the beneficial effect of a physically active lifestyle in counteracting aberrant cancer-related gene expression programs by improving the redox buffering capacity.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.06.037DOI Listing
November 2020

Comorbidity indices in people with HIV and considerations for coronavirus disease 2019 outcomes.

AIDS 2020 10;34(12):1795-1800

Institute for Global Health, University College London.

Objective: To determine comorbidity indices in people with HIV (PWH) and lifestyle-similar HIV-negative controls.

Design: Cross-sectional analysis of the Pharmacokinetic and clinical Observations in PeoPle over fiftY cohort study in the United Kingdom and Ireland.

Methods: The Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index and the Comorbidity Burden Index were compared between older PWH and HIV-negative controls using the Mann-Whitney U test; the magnitude of the difference between groups was quantified using the r effect size.

Results: The 699 PWH and 304 HIV-negative controls were predominantly male (87.5% vs. 64.0%), white (86.3% vs. 90.0%) and had median ages of 57 and 58 years, respectively. Among PWH, the median (interquartile range) CD4 T-cell count was 624 (475, 811) cells/μl; 98.7% were on antiretroviral therapy. The median (interquartile range) ECI was 0 (0, 8) and 0 (-3, 1), Charlson Comorbidity Index was 2 (1, 5) and 1 (0, 1) and Comorbidity Burden Index 8.6 (2.2, 16.8) and 5.9 (0.6, 10.8), respectively. While all three indices were significantly higher in PWH than in controls (P < 0.001 for each), the magnitude of the differences between the two groups were small to medium, with effect sizes (95% confidence interval) of 0.21 (0.16, 0.27), 0.38 (0.32, 0.42) and 0.18 (0.11, 0.23), respectively.

Conclusion: These three comorbidity indices are higher in PWH compared with HIV-negative controls, although the magnitude of differences between groups were small. Differences in the ECI, reportedly associated with poorer coronavirus disease 2019 outcomes, were driven by more individuals with HIV being within the higher end of the range.
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http://dx.doi.org/10.1097/QAD.0000000000002606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493769PMC
October 2020

Is Complete Pathologic Response in Pancreatic Cancer Overestimated? A Systematic Review of Prospective Studies.

J Gastrointest Surg 2020 10 24;24(10):2336-2348. Epub 2020 Jun 24.

General Surgery Unit, Department of Medical and Surgical Sciences and Translational Medicine, St. Andrea University Hospital, Sapienza University of Rome, Via di Grottorassa 1035, 00168, Rome, Italy.

Background: In literature, percentages of pathologic complete response (pCR) in patients presenting with resectable (RES), borderline resectable (BLR) or locally advanced (LA) pancreatic cancer (PaC) after neoadjuvant treatment (NADT) are variable, ranging 0-33%. Those data come mostly from retrospective reviews of single centres. The objective of this systematic review is to assess the incidence of pCR.

Methods: Following the criteria of the PRISMA statement, a literature search was conducted looking for prospective papers focusing on neoadjuvant treatment in PaC. Retrospective papers, other than ductal carcinoma histologies and trials including metastatic patients, were excluded from the present review. Data extraction was carried out by 3 independent investigators. Meta-analysis was performed with ProMeta3 Software (Internovi, 2015). PROSPERO registry: CRD42018095641.

Results: The literature search of Embase, Cochrane and Medline with the terms "neoadjuvant OR preoperative", "pancreatic OR pancreas" and "cancer OR adenocarcinoma OR tumor" led to the identification of 3128 papers. We restricted the search to humans, last 10 years and English language articles resulting in 1158 eligible articles to review. Extended paper revision led to the inclusion of 27 papers. Complete pathologic response ranged 0-11.11%, at the meta-analysis 4% (95% CI 3-5%), in prospective studies 0-9.09% and in prospective databases 1.63-11.11%.

Conclusions: Pathologic complete response in pancreatic cancer is actually infrequent: high-quality studies provide a more reliable picture of neoadjuvant effects, high rates of pCR are reported in selected retrospective studies but it is overestimated.
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http://dx.doi.org/10.1007/s11605-020-04697-1DOI Listing
October 2020

Associations Between Widespread Pain and Sleep Quality in People With HIV.

J Acquir Immune Defic Syndr 2020 09;85(1):106-112

Minneapolis Veterans Affairs Health Care System, University of Minnesota, Minnesota, MN.

Background: We investigate the association of widespread pain with sleep quality among people with HIV and HIV-negative controls.

Setting: UK-based cohort.

Methods: Pain information was collected through a pain mannikin identifying affected body sites; pain was classified as widespread if pain was reported in ≥4 of 5 body regions and in ≥7 of 15 body sites, and as regional otherwise. Sleep was assessed a median of 3.2 years later through 7-night actigraphy and through self-reported assessments of sleep quality. Chi-squared tests, Kruskal-Wallis tests, and linear/logistic regression considered associations between pain extent and sleep quality.

Results: Of the 414 participants, 74 (17.9%) reported widespread and 189 (45.7%) regional pain. Although there were few clear associations between actigraphy outcomes and pain extent, those with widespread and regional pain consistently reported poorer sleep quality on all self-reported measures than those with no pain. Median (interquartile range) insomnia severity index and Patient-reported Outcomes Measurement Information System (PROMIS) for sleep disturbance and sleep-related impairment scores were 12 (7-16), 55.3 (48.0-58.9), and 57.2 (48.9-61.3), respectively, for those with widespread pain, 8 (4-13), 51.2 (45.5-58.3), and 50.3 (43.6-56.1) for those with regional pain, and 5 (2-9), 47.9 (42.9-54.3), and 45.5 (41.4-50.3) for those with no pain (all P values 0.0001). Associations remained strong after adjustment for HIV status and other confounders, and were reduced but remained significant, after adjustment for depressive symptoms.

Conclusions: Widespread pain was not associated with objective measures of sleep but was strongly associated with self-reported assessments of sleep quality in people with HIV.
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http://dx.doi.org/10.1097/QAI.0000000000002410DOI Listing
September 2020

Factors associated with obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort: an observational cross-sectional analysis.

HIV Med 2020 08 20;21(7):441-452. Epub 2020 Apr 20.

Centre for Experimental Pathogen Host Research (CEPHR), University College Dublin, Dublin, Ireland.

Objectives: The aims of the study were to describe the prevalence of obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and sociodemographic, clinical and HIV-specific factors and quality of life (QoL).

Methods: A cross-sectional analysis was carried out of baseline data from the three groups ["older" people with HIV infection (PWH) aged ≥ 50 years, "younger" PWH aged < 50 years and HIV-negative controls aged ≥ 50 years] within the POPPY cohort. Obesity was defined as a body mass index (BMI) > 30 kg/m .

Results: A total of 1361 subjects were included in the study, of whom 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4 T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. The presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes and hypertension, but lower odds of having osteopenia/osteoporosis, irrespective of HIV status.

Conclusions: Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese, and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined.
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http://dx.doi.org/10.1111/hiv.12857DOI Listing
August 2020
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