HIV-1 latent reservoir: size matters.

More than 35 million people remain infected with HIV-1. Upon antiretroviral therapy cessation, HIV-1-positive individuals systematically fail to achieve sustained virological remission, revealing the presence of a reservoir. This reservoir takes into account anatomical sanctuaries where HIV-1 continues to replicate, and latently infected cells also known as the latent reservoir (LR). A better understanding of the nature and features of the LR and its quantification are crucial to evaluate the efficiency of therapeutic strategies aiming at purging HIV-1. Culture- and PCR-based assays have already been implemented to measure the LR, and new assays are continuously being developed. In this review, we will discuss these methods highlighting the difficulties to accurately measure the LR, one main obstacle in curing HIV-1

A Computer Modelling Approach To Evaluate the Accuracy of Microsatellite Markers for Classification of Recurrent Infections during Routine Monitoring of Antimalarial Drug Efficacy

Anti-malarial drugs have long half-lives, so clinical trials to monitor their efficacy require long durations of follow-up to capture drug failure that may only become patent weeks after treatment. Reinfections often occur during follow-up so robust methods of distinguishing drug failures (recrudescence) from emerging new infections are needed to produce accurate failure rate estimates. "Molecular correction" aims to achieve this by comparing the genotypes between a patient's pre-treatment (initial) blood sample and any infection that occurs during follow-up, 'matching' genotypes indicating a drug failure. We use an in-silico approach to show that the widely used "match counting" method of molecular correction with microsatellite markers is likely to be highly unreliable and may lead to gross under- or over-estimates of true failure rates depending on the choice of matching criterion. A Bayesian algorithm for molecular correction has been previously developed and utilized for analysis of in vivo efficacy trials. We validated this algorithm using in silico data and showed it had high specificity and generated accurate failure rate estimates. This conclusion was robust for multiple drugs, different levels of drug failure rate, different levels of transmission intensity in the study sites, and microsatellite genetic diversity. The Bayesian algorithm was inherently unable to accurately identify low-density recrudescence that occurred in a small number of patients, but this did not appear to compromise its utility as a highly effective molecular correction method for analysing microsatellite genotypes. Strong consideration should be given to using Bayesian methodology for obtaining accurate failure rate estimates during routine monitoring trials of antimalarial efficacy that use microsatellite marker

A systematic analysis of preprints in Trauma & Orthopaedic surgery

AIMS Preprint servers allow authors to publish full-text manuscripts or interim findings prior to undergoing peer review. Several preprint servers have extended their services to biological sciences, clinical research, and medicine. The purpose of this study was to systematically identify and analyze all articles related to Trauma & Orthopaedic (T&O) surgery published in five medical preprint servers, and to investigate the factors that influence the subsequent rate of publication in a peer-reviewed journal. METHODS All preprints covering T&O surgery were systematically searched in five medical preprint servers (medRxiv, OSF Preprints, Preprints.org, PeerJ, and Research Square) and subsequently identified after a minimum of 12 months by searching for the title, keywords, and corresponding author in Google Scholar, PubMed, Scopus, Embase, Cochrane, and the Web of Science. Subsequent publication of a work was defined as publication in a peer-reviewed indexed journal. The rate of publication and time to peer-reviewed publication were assessed. Differences in definitive publication rates of preprints according to geographical origin and level of evidence were analyzed. RESULTS The number of preprints increased from 2014 to 2020 (p < 0.001). A total of 38.6% of the identified preprints (n = 331) were published in a peer-reviewed indexed journal after a mean time of 8.7 months (SD 5.4 (1 to 27)). The highest proportion of missing subsequent publications was in the preprints originating from Africa, Asia/Middle East, and South America, or in those that covered clinical research with a lower level of evidence (p < 0.001). CONCLUSION Preprints are being published in increasing numbers in T&O surgery. Depending on the geographical origin and level of evidence, almost two-thirds of preprints are not subsequently published in a peer-reviewed indexed journal after one year. This raises major concerns regarding the dissemination and persistence of potentially wrong scientific work that bypasses peer review, and the orthopaedic community should discuss appropriate preventive measures.Cite this article: Bone Jt Open 2022;3(7):582-588

Diffusion-Weighted Imaging Hyperintensities in Subtypes of Acute Intracerebral Hemorrhage: Meta-Analysis

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) hyperintensities in intracerebral hemorrhage (ICH) are associated with increased risk of recurrent ICH, cognitive impairment, and death, but whether these lesions are specific to a subtype of ICH remains uncertain. We investigated the association between DWI lesions and ICH subtype and explored the risk factors for DWI lesions. METHODS: In a systematic review of ICH studies, we identified those reporting prevalence of DWI lesions. Two reviewers independently assessed study eligibility and risk of bias and collected data. We determined the pooled prevalence of DWI lesions within 90 days after ICH onset for cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH using random-effects meta-analysis. We calculated odds ratios to compare prevalence of DWI lesions by ICH subtype and to assess risk factors for DWI lesions. RESULTS: Eleven studies (1910 patients) were included. The pooled prevalence of DWI lesions was 18.9% (95% CI, 11.1–26.7) in cerebral amyloid angiopathy- and 21.0% (95% CI, 15.3–26.6) in hypertensive angiopathy-related ICH. There was no difference in the prevalence of DWI lesions between cerebral amyloid angiopathy- (64/292 [21.9%]) and hypertensive angiopathy-related ICH (79/370 [21.4%]; odds ratio, 1.25; 95% CI, 0.73–2.15) in the 5 studies reporting data on both ICH pathogeneses. In all ICH, presence of DWI lesions was associated with neuroimaging features of microangiopathy (leukoaraiosis extension, previous ICH, and presence, and number of microbleeds) but not with vascular risk factors or the use of antithrombotic therapies. CONCLUSIONS: Prevalence of DWI lesions in acute ICH averages 20%, with no difference between cerebral amyloid angiopathy- and hypertensive angiopathy-related ICH. Detection of DWI lesions may add valuable information to assess the progression of the underlying microangiopathy

Excessive femoral torsion is not associated with patellofemoral pain or instability if TKA is functionally aligned and the patella denervated

PURPOSE Recent data suggest that individual morphologic factors should be respected to restore preoperative patellofemoral alignment and thus reduce the likelihood of anterior knee pain. The goal of this study was to investigate the effect of excessive femoral torsion (FT) on clinical outcome of TKA. METHODS Patients who underwent TKA and complete preoperative radiographic evaluation including a long-leg radiograph and CT scan were included. 51 patients showed increased FT of > 20° and were matched for age/sex to 51 controls (FT < 20°). Thirteen patients were lost to follow-up. Thirty-eight matched pairs were compared after a 2 year follow-up clinically (Kujala and patellofemoral score for TKA) and radiographically (FT, frontal leg axis, TT-TG, patellar thickness, patellar tilt, and lateral displacement of patella). Functional alignment of TKA was performed (hybrid-technique). All patellae were denervated but no patella was resurfaced. RESULTS There was no significant difference between clinical scores two years after surgery between patients with normal and excessive FT (n.s.). Kujala score was 64.3 ± 16.7 versus 64.8 ± 14.4 (n.s.), and patellofemoral score for TKA was 74.3 ± 21 versus 78.5 ± 20.7 (n.s.) for increased FT group and control group, respectively. There was no correlation between preoperative FT and clinical scores. Other radiographic parameters were similar between both groups. No correlations between clinical outcomes and preoperative/postoperative frontal leg axis or total leg axis correction were found (n.s.). CONCLUSION If the leg axis deformity is corrected to a roughly neutral alignment during cemented TKA, including patellar denervation, then excessive FT was not associated with patellofemoral pain or instability. LEVEL OF EVIDENCE Prospective comparative study, level II

Osteoconductive Scaffold Placed at the Femoral Tunnel Aperture in Hamstring Tendon ACL Reconstruction: A Randomized Controlled Trial

BACKGROUND: Bone tunnel enlargement after single-bundle anterior cruciate ligament reconstruction remains an unsolved problem that complicates revision surgery. HYPOTHESIS: Positioning of an osteoconductive scaffold at the femoral tunnel aperture improves graft-to-bone incorporation and thereby decreases bone tunnel widening. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In a 1:1 ratio, 56 patients undergoing primary anterior cruciate ligament reconstruction were randomized to receive femoral fixation with cortical suspension fixation and secondary press-fit fixation at the tunnel aperture of the tendon graft only (control) or with augmentation by an osteoconductive scaffold (intervention). Adverse events, patient-reported outcomes, and passive knee stability were recorded over 2 years after the index surgery. Three-dimensional bone tunnel widening was assessed using computed tomography at the time of surgery and 4.5 months and 1 year postoperatively. RESULTS: The intervention group exhibited a similar number of adverse events as the control group (8 vs 10; P = .775) including 2 partial reruptures in both groups. The approach was feasible, although 1 case was encountered where the osteoconductive scaffold was malpositioned without adversely affecting the patient's recovery. There was no difference between the intervention and control groups in femoral bone tunnel enlargement, as expressed by the relative change in tunnel volume from surgery to 4.5 months (mean ± SD, 36% ± 25% vs 40% ± 25%; P = .644) and 1 year (19% ± 20% vs 17% ± 25%; P =.698). CONCLUSION: Press-fit graft fixation with an osteoconductive scaffold positioned at the femoral tunnel aperture is safe but does not decrease femoral bone tunnel enlargement at postoperative 1 year. REGISTRATION: NCT03462823 (ClinicalTrials.gov identifier)

Rescue and homogenization of 140 years of glacier mass balance data in Switzerland

Glacier monitoring in Switzerland has resulted in some of the longest and most complete data series globally. Mass balance observations at individual locations, starting in the 19th century, are the backbone of the monitoring as they represent the raw and original glaciological data demonstrating the response of snow accumulation and snow/ice melt to changes in climate forcing. So far, however, the variety of sources of historic measurements has not been systematically processed and documented. Here, we present a new complete and extensive point glacier mass balance dataset for the Swiss Alps that provides attributes for data quality and corresponding uncertainties. Original sources were digitized or re-assessed to validate or to correct existing entries and to identify metadata. The sources of data are highly diverse and stem from almost 140 years of records, originating from handwritten field notes, unpublished project documents, various digital sources, published reports, and meta-knowledge of the observers. The project resulted in data series with metadata for 63 individual Swiss glaciers, including more than 60 000 point observations of mass balance. Data were systematically analysed and homogenized, e.g. by supplementing partly missing information based on correlations inferred from direct measurements. A system to estimate uncertainty in all individual observations was developed indicating that annual point balance is measured with a typical error of 0.07 m water equivalent (w.e.), while the average error in winter snow measurements is 0.20 m w.e. Our dataset permits further investigating the climate change impacts on Swiss glaciers. Results show an absence of long-term trends in snow accumulation over glaciers while melt rates have substantially increased over the last 3 decades. The complete dataset is available at DOI https://doi.org/10.18750/massbalance.point.2021.r2021 (GLAMOS, 2021).</p

Carbon fibre/polyether ether ketone (CF/PEEK) implants in orthopaedic oncology

Background: Radiation therapy is an important therapeutic element in musculoskeletal tumours, especially when encountering multiple or painful lesions. In osteolytic lesions, a surgical stabilization with implants is often required. However, metallic implants not only complicate the CT-based planning of a subsequent radiation therapy, but also have an uncontrollable dose-modulating effect in adjuvant radiotherapy. In addition, follow-up imaging and the diagnosis of local recurrences are often obscured by metallic artefacts. Radiolucent implants consisting of carbon/polyether ether ketone (CF/PEEK) therefore facilitate adjuvant radiation therapy and follow-up imaging of bone lesions. We hereby present clinical cases with application of CF/PEEK implants in orthopaedic tumour surgery. Methods: We report a single-centre experience of three selected patients with surgical stabilization of osteolytic bone lesions using CF/PEEK implants. Detailed information about the clinical presentation, preoperative considerations, surgical procedures and postoperative results is provided for each case. Results: One spinal lesion (T12 vertebral body), one lesion of the upper extremity (humerus) and one of the lower extremities (tibia) were surgically stabilized with use of CF/PEEK implants. With a mean follow-up of 12 months (range 6-25 months), no adverse events were observed. Two patients received adjuvant radiotherapy. Follow-up imaging was obtained in all patients. Conclusion: The applicability of CF/PEEK implants in orthopaedic tumour surgery is good with respect to postoperative follow-up imaging, application of adjuvant radiotherapy and intraoperative handling. As a result of the unique material properties, oncological patients might particularly benefit from CF/PEEK implants. Keywords: Bone metastases; CF/PEEK; Imaging; Orthopaedic oncology; Polyether ether ketone; Radiation therapy