Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

SARS‐CoV‐2 and human milk: What is the evidence?

The novel coronavirus SARS‐CoV‐2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS‐CoV‐2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS‐CoV‐2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS‐CoV in human milk (it was negative); and no published data on MERS‐CoV and human milk. We identified 13 studies reporting human milk tested for SARS‐CoV‐2; one study (a non‐peer‐reviewed preprint) detected the virus in one milk sample, and another study detected SARS‐CoV‐2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS‐CoV‐2) during breastfeeding are discussed.     

Is there a reduction in risk of revision when 36-mm heads instead of 32 mm are used in total hip arthroplasty for patients with proximal femur fractures?: A matched analysis of 5,030 patients with a median of 2.5 years’ follow-up between 2006 and 2016 in the Nordic Arthroplasty Register Association

Background and purpose — 32-mm heads are widely used in total hip arthroplasty (THA) in Scandinavia, while the proportion of 36-mm heads is increasing as they are expected to increase THA stability. We investigated whether the use of 36-mm heads in THA after proximal femur fracture (PFF) is associated with a lower risk of revision compared with 32-mm heads.Patients and methods — We included 5,030 patients operated with THA due to PFF with 32- or 36-mm heads from the Nordic Arthroplasty Register Association database. Each patient with a 36-mm head was matched with a patient with a 32-mm head, using propensity score. The patients were operated between 2006 and 2016, with a metal or ceramic head on a polyethylene bearing. Cox proportional hazards models were fitted to estimate the unadjusted and adjusted hazard ratio (HR) with 95% confidence intervals (CI) for revision for any reason and revision due to dislocation for 36-mm heads compared with 32-mm heads.Results — 36-mm heads had an HR of 0.9 (CI 0.7–1.2) for revision for any reason and 0.8 (CI 0.5–1.3) for revision due to dislocation compared with 32-mm heads at a median follow-up of 2.5 years (interquartile range 1–4.4).Interpretation — We were not able to demonstrate any clinically relevant reduction of the risk of THA revision for any reason or due to dislocation when 36-mm heads were used versus 32-mm. Residual confounding due to lack of data on patient comorbidities and body mass index could bias our results.

During the past years total hip arthroplasty (THA) has become the preferred treatment option for displaced femoral neck fractures in even younger (55–64 years) patients (Rogmark et al. 2017). Previous studies have shown an increased risk of revision, especially due to dislocation, in patients receiving THA after proximal femur fracture (PFF) compared with patients operated due to primary osteoarthritis (OA) (Conroy et al. 2008, Hailer et al. 2012). The risk of THA dislocation in fracture patients varies widely from as low as 5% (Tabori-Jensen et al. 2019), especially when dual mobility cups (DMCs) are used, up to 6–18% (Burgers et al. 2012, Johansson 2014, Noticewala et al. 2018) with conventional cups. The risk of THA revision due to dislocation has been reported as even lower, ranging from 0.5 to 0.7% in national register studies (Conroy et al. 2008, Hailer et al. 2012), as not all unstable THAs are revised. According to the above-mentioned studies, increased age, male sex, the use of a posterior approach, and smaller head sizes are associated with increased risk of revision due to dislocation. To counteract the risk of dislocation, bigger head sizes have been used as they increase the impingement-free range of motion (Burroughs et al. 2005, Tsuda et al. 2016) and jumping distance of THA (Sariali et al. 2009). During the past years, the use of larger heads in THA has increased with 28-mm continuously declining and 32- and 36-mm increasing (Tsikandylakis et al. 2018b). However, register studies performed on patients with displaced femoral neck fracture (Jameson et al. 2012, Cebatorius et al. 2015) have not demonstrated any superiority of larger heads over smaller ones regarding risk of revision, especially due to dislocation. This effect has only been demonstrated in studies performed on a case mix of hip diagnoses that have reported an increased risk of revision due to dislocation when 28-mm or smaller heads are used compared with 32-mm or larger heads (Hailer et al. 2012, Kostensalo et al. 2013).Most of the above-mentioned register studies have used 28-mm heads as reference, which are rarely used nowadays (Tsikandylakis et al. 2018b). Patients receiving THA after PFF have a higher risk for revision than patients with OA and should preferably be studied separately, setting 32 mm as contemporary standard of reference. We therefore investigated if increasing head size from 32 to 36 mm is associated with a decreased risk of revision, especially due to dislocation, in patients with PFF in the Nordic Arthroplasty Register Association (NARA) database. We hypothesized that the risk is lower when 36-mm heads are used.