Identification and analysis of co-disease genes between COVID-19 and osteoarthritis (preprint)

Background: The molecular mechanisms of corona virus disease 2019 (COVID-19) and osteoarthritis (OA) are unclear, and there is an urgent need to identify new biomarkers and explore their potential molecular mechanisms in COVID-19 and OA. Methods: The GSE57218, GSE157103 training sets and the GSE82107, GSE171110 validation sets were acquired via gene expression omnibus (GEO) database. First, differentially expressed genes (DEGs) between disease and normal samples in the GSE57218 and GSE157103 training sets were respectively sifted out by differential expression analysis. The modules with the highest correlation with OA and normal, COVID-19 and non COVID-19 were gained by weighted gene co-expression network analysis (WGCNA), individually. Then, OA-DEGs were intersected with the module genes that had significant correlation with OA, and COVID-19-DEGs were intersected with the module genes which were dramatically correlated with COVID-19 to yield OA-intersected genes and COVID-19 intersected genes, respectively. The OA-intersected genes and COVID-19 intersected genes were intersected to yield candidate genes, and they were analyzed for function enrichment analysis. Next, the seven algorithms (Closeness, MCC, Degree, MNC, Radality, Stress and EPC) were performed on candidate genes to sift out biomarkers. Finally, we constructed the competing endogenous RNA (ceRNA), transcription factor (TF)/miRNA-mRNA and drug-target regulatory networks. Results:There were 1135 OA-DEGs and 4336 COVID-19-DEGs between disease and normal samples in the GSE57218 and GSE157103 training sets, respectively. The pink, blue and brown modules had significant correlations with OA in the GSE57218 training set, while in the GSE157103 training set, the pink and brown modules were notably correlated with COVID-19. We finally yield 715 OA-intersected genes and 2282 COVID-19-intersected genes. After intersecting the above two intersected genes, we gained 106 candidate genes, and they were involved in ADP metabolic process, nucleoside diphosphate phosphorylation, etc.. The 7 biomarkers, namely AK1, APP, ENO1, TPI1, HSP90B1, HSPB1 and ESR1, were acquired based on seven algorithms. Finally, we successfully constructed the ceRNA, TF/miRNA-mRNA and drug-target networks. Conclusion: Through bioinformatic methods, we explored the biomarkers (AK1, APP, ENO1, TPI1, HSP90B1, HSPB1 and ESR1) of COVID-19 combined OA, providing new ideas for studies related to molecular mechanisms and treatment of comorbidity.

Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19.

Background: Corona Virus Disease 2019 (COVID-19) and Osteoarthritis (OA) are diseases that seriously affect the physical and mental health and life quality of patients, particularly elderly patients. However, the association between COVID-19 and osteoarthritis at the genetic level has not been investigated. This study is intended to analyze the pathogenesis shared by OA and COVID-19 and to identify drugs that could be used to treat SARS-CoV-2-infected OA patients. Methods: The four datasets of OA and COVID-19 (GSE114007, GSE55235, GSE147507, and GSE17111) used for the analysis in this paper were obtained from the GEO database. Common genes of OA and COVID-19 were identified through Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen key genes, which were analyzed for expression patterns by single-cell analysis. Finally, drug prediction and molecular docking were carried out using the Drug Signatures Database (DSigDB) and AutoDockTools. Results: Firstly, WGCNA identified a total of 26 genes common between OA and COVID-19, and functional analysis of the common genes revealed the common pathological processes and molecular changes between OA and COVID-19 are mainly related to immune dysfunction. In addition, we screened 3 key genes, DDIT3, MAFF, and PNRC1, and uncovered that key genes are possibly involved in the pathogenesis of OA and COVID-19 through high expression in neutrophils. Finally, we established a regulatory network of common genes between OA and COVID-19, and the free energy of binding estimation was used to identify suitable medicines for the treatment of OA patients infected with SARS-CoV-2. Conclusion: In the present study, we succeeded in identifying 3 key genes, DDIT3, MAFF, and PNRC1, which are possibly involved in the development of both OA and COVID-19 and have high diagnostic value for OA and COVID-19. In addition, niclosamide, ciclopirox, and ticlopidine were found to be potentially useful for the treatment of OA patients infected with SARS-CoV-2.

Plasma Levels of MMPs and TIMP-1 in Patients with Osteoarthritis After Recovery from COVID-19.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPS) play a key role in the pathogenesis of osteoarthritis (OA). Recent research showed the involvement of some MMPs in COVID-19, but the results are limited and contradictory. OBJECTIVE: In this study, we investigated the levels of MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10) and TIMP-1 in the plasma of patients with OA after recovery from COVID- 19. METHODS: The experiment involved patients aged 39 to 80 diagnosed with knee OA. All study participants were divided into three research groups: the control group included healthy individuals, the group OA included patients with enrolled cases of OA, and the third group of OA and COVID-19 included patients with OA who recovered from COVID-19 6-9 months ago. The levels of MMPs and TIMP-1 were measured in plasma by enzyme-linked immunosorbent assay. RESULTS: The study showed a change in the levels of MMPs in patients with OA who had COVID- 19 and those who did not have a history of SARS-CoV-2 infection. Particularly, patients with OA who were infected with coronavirus established an increase in MMP-2, MMP-3, MMP-8, and MMP-9, compared to healthy controls. Compared to normal subjects, a significant decrease in MMP-10 and TIMP-1 was established in both groups of patients with OA and convalescent COVID-19. CONCLUSION: Thus, the results suggest that COVID-19 can affect the proteolysis-antiproteolysis system even after a long postinfectious state and may cause complications of existing musculoskeletal pathologies.

Bioinformatics and system biology approach to identify potential common pathogenesis for COVID-19 infection and osteoarthritis.

A growing of evidence has showed that patients with osteoarthritis (OA) had a higher coronavirus 2019 (COVID-19) infection rate and a poorer prognosis after infected it. Additionally, scientists have also discovered that COVID-19 infection might cause pathological changes in the musculoskeletal system. However, its mechanism is still not fully elucidated. This study aims to further explore the sharing pathogenesis of patients with both OA and COVID-19 infection and find candidate drugs. Gene expression profiles of OA (GSE51588) and COVID-19 (GSE147507) were obtained from the Gene Expression Omnibus (GEO) database. The common differentially expressed genes (DEGs) for both OA and COVID-19 were identified and several hub genes were extracted from them. Then gene and pathway enrichment analysis of the DEGs were performed; protein-protein interaction (PPI) network, transcription factor (TF)-gene regulatory network, TF-miRNA regulatory network and gene-disease association network were constructed based on the DEGs and hub genes. Finally, we predicted several candidate molecular drugs related to hub genes using DSigDB database. The receiver operating characteristic curve (ROC) was applied to evaluate the accuracy of hub genes in the diagnosis of both OA and COVID-19. In total, 83 overlapping DEGs were identified and selected for subsequent analyses. CXCR4, EGR2, ENO1, FASN, GATA6, HIST1H3H, HIST1H4H, HIST1H4I, HIST1H4K, MTHFD2, PDK1, TUBA4A, TUBB1 and TUBB3 were screened out as hub genes, and some showed preferable values as diagnostic markers for both OA and COVID-19. Several candidate molecular drugs, which are related to the hug genes, were identified. These sharing pathways and hub genes may provide new ideas for further mechanistic studies and guide more individual-based effective treatments for OA patients with COVID-19 infection.

Inequalities in provision of hip and knee replacement surgery for osteoarthritis by age, sex, and social deprivation in England between 2007-2017: A population-based cohort study of the National Joint Registry.

BACKGROUND: While the United Kingdom National Health Service aimed to reduce social inequalities in the provision of joint replacement, it is unclear whether these gaps have reduced. We describe secular trends in the provision of primary hip and knee replacement surgery between social deprivation groups. METHODS AND FINDINGS: We used the National Joint Registry to identify all hip and knee replacements performed for osteoarthritis from 2007 to 2017 in England. The Index of Multiple Deprivation (IMD) 2015 was used to identify the relative level of deprivation of the patient living area. Multilevel negative binomial regression models were used to model the differences in rates of joint replacement. Choropleth maps of hip and knee replacement provision were produced to identify the geographical variation in provision by Clinical Commissioning Groups (CCGs). A total of 675,342 primary hip and 834,146 primary knee replacements were studied. The mean age was 70 years old (standard deviation: 9) with 60% and 56% of women undergoing hip and knee replacements, respectively. The overall rate of hip replacement increased from 27 to 36 per 10,000 person-years and knee replacement from 33 to 46. Inequalities of provision between the most (reference) and least affluent areas have remained constant for both joints (hip: rate ratio (RR) = 0.58, 95% confidence interval [0.56, 0.60] in 2007, RR = 0.59 [0.58, 0.61] in 2017; knee: RR = 0.82 [0.80, 0.85] in 2007, RR = 0.81 [0.80, 0.83] in 2017). For hip replacement, CCGs with the highest concentration of deprived areas had lower overall provision rates, and CCGs with very few deprived areas had higher provision rates. There was no clear pattern of provision inequalities between CCGs and deprivation concentration for knee replacement. Study limitations include the lack of publicly available information to explore these inequalities beyond age, sex, and geographical area. Information on clinical need for surgery or patient willingness to access care were unavailable. CONCLUSIONS: In this study, we found that there were inequalities, which remained constant over time, especially in the provision of hip replacement, by degree of social deprivation. Providers of healthcare need to take action to reduce this unwarranted variation in provision of surgery.

Did COVID-19 impact osteoarthritis - clinical perspective?

PURPOSE OF REVIEW: To assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on patients with osteoarthritis (OA). RECENT FINDINGS: The COVID-19 pandemic negatively affected patients with OA irrespective of them contracting the infection. Patients with OA had a disruption in access to the healthcare system, which resulted in delays in joint replacement surgeries from cancellations of elective surgical procedures. On the other hand, the pandemic accelerated the drive towards telemedicine and telerehabilitation, with many nonurgent services being delivered remotely whenever possible. Cross-sectional studies showed that the majority of patients with OA were willing to accept the increased risks of contracting the COVID-19 infection and proceed with elective joint replacement surgeries. SUMMARY: The American College of Rheumatology and the European League Against Rheumatism issued guidelines for managing immune-mediated rheumatic diseases during the pandemic. However, these guidelines did not include recommendations for patients with OA.Healthcare providers, including physical therapists, should aim to schedule more frequent telemedicine follow-up appointments to maximize medical management while patients await elective joint procedures.

Clinical evaluation of total hip arthroplasty for osteoarthropathy secondary to septic hip arthritis.

To investigate the clinical efficacy and prognosis of total hip arthroplasty (THA) in patients with osteoarthropathy secondary to septic hip arthritis. A total of 100 patients with osteoarthropathy secondary to septic hip arthritis who underwent surgery in our hospital from December 2010 to December 2021 were selected. Operative data were summarized. Moreover, preoperative and postoperative differences in Harris score, Western Ontario and McMaster Universities Osteoarthritis Index score, Visual Analogue Scale score, hip mobility were compared. Due to hospital transfer, the epidemic of COVID-2019 and other reasons, 10 patients were lost to follow-up and finally 90 patients were recorded. According to the results, the mean operation time (OT) was 1.78 ± 0.32 (hour), the mean intraoperative blood loss (BL) was 586.62 ± 31.66 (mL), the mean red blood cell (RBC) transfusion was 3.84 ± 0.75 (U), and 2 cases were positive, and 88 cases were negative for Trendelenburg sign. Postoperatively, the unequal length of the lower limbs and the Visual Analogue Scale score were significantly lower than that of the preoperative, while the Western Ontario and McMaster Universities Osteoarthritis Index score, Harris score, and hip joint range of motion were significantly higher than those of the preoperative (P < .05). At the last follow-up, all the incisions healed with no deep infections, 1 case suffered from transient sciatic nerve palsy, 2 cases had intermuscular venous thrombosis, and 2 cases who occurred hip dislocation recovered after treatment. THA surgery for osteoarthropathy secondary to septic hip arthritis has a good effect, relieving the patient's pain effectively, improving prognosis and joint mobility. For osteoarthropathy secondary to septic hip arthritis, THA may be meaningful in terms of prognosis.

Osteoarthritis year in review 2022: biology.

The field of osteoarthritis (OA) biology is rapidly evolving and brilliant progress has been made this year as well. Landmark studies of OA biology published in 2021 and early 2022 were selected through PubMed search by personal opinion. These papers were classified by their molecular mechanisms, and it was largely divided into the intracellular signaling mechanisms and the inter-compartment interaction in chondrocyte homeostasis and OA progression. The intracellular signaling mechanisms involving OA progression included (1) Piezo1/transient receptor potential channels of the vanilloid subtype (TRPV) 4-mediated calcium signaling, (2) mechanical load-F-box and WD repeat domain containing 7 (FBXW7) in chondrocyte senescence, (3) mechanical loading-primary cilia-hedgehog signaling, (4) low grade inflammation by toll-like receptor (TLR)-CD14-lipopolysaccharide-binding protein (LBP) complex and inhibitor of NF-κB kinase (IKK) ß-nuclear factor kappa B (NF-κB) signaling, (5) selenium pathway and reactive oxygen species (ROS) production, (6) G protein-coupled receptor (GPCR) and cyclic adenosine monophosphate (cAMP) signaling, (7) peroxisome proliferator-activated receptor α (PPARα)-acyl-CoA thioesterase 12 (ACOT12)-mediated de novo lipogenesis and (8) hypoxia-disruptor of telomeric silencing 1-like (DOT1L)-H3-lysine 79 (H3K79) methylation pathway. The studies on inter-compartment or intercellular interaction in OA progression included the following subjects; (1) the anabolic role of lubricin, glycoprotein from superficial zone cells, (2) osteoclast-chondrocyte interaction via exosomal miRNA and sphingosine 1-phosphate (S1P), (3) senescent fibroblast-like synoviocyte and chondrocyte interaction, (4) synovial macrophage and chondrocyte interaction through Flightless I, (5) αV integrin-mediated transforming growth factor beta (TGFß) activation by mechanical loading, and (6) osteocytic TGFß in subchondral bone thickening. Despite the disastrous Covid-19 pandemic, many outstanding studies have expanded the boundary of OA biology. They provide both critical insight into the pathophysiology as well as clues for the treatment of OA.

Risk of COVID-19 Diagnosis and Hospitalisation in Patients with Osteoarthritis or Back Pain Treated with Ibuprofen Compared to Other NSAIDs or Paracetamol: A Network Cohort Study.

OBJECTIVE: We aimed to investigate whether ibuprofen use, compared with other non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs), cyclooxygenase-2 inhibitors (COX-2i) or paracetamol, increases the risk of coronavirus disease 2019 (COVID-19) diagnosis or hospitalisation. DESIGN: A prevalent user and active comparator cohort study. SETTING: Two US claims databases (Open Claims and PharMetrics Plus) mapped to the Observational Medical Outcomes Partnership Common Data Model. PARTICIPANTS: Insured patients with a history of osteoarthritis or back pain and receiving ibuprofen, other ns-NSAIDs, COX-2i or paracetamol between 1 November, 2019 and 31 January, 2020 (study enrolment window 1) or between 1 February, 2020 and 31 October, 2020 (study enrolment window 2). MAIN OUTCOME MEASURES: Large-scale propensity score matching and empirical calibration were used to minimise confounding. Incidence and hazard ratios of COVID-19 diagnosis and hospitalisation according to drug/s use were estimated and pooled in the same study period across data sources using a fixed-effects meta-analysis. Index treatment episode was the primary risk evaluation window, censored at the time of discontinuation. RESULTS: A total of 633,562 and 1,063,960 participants were included in periods 1 and 2, respectively, for the ibuprofen versus ns-NSAIDs comparison, 311,669 and 524,470 for ibuprofen versus COX-2i, and 492,002 and 878,598 for ibuprofen versus paracetamol. Meta-analyses of empirically calibrated hazard ratios revealed no significantly differential risk of COVID-19 outcomes in users of ibuprofen versus any of the other studied analgesic classes: hazard ratios were 1.13 (0.96-1.33) for the ibuprofen-ns-NSAIDs comparison, 1.03 (0.83-1.28) for the ibuprofen-COX-2i comparison and 1.13 (0.74-1.73) for ibuprofen-paracetamol comparison on COVID-19 diagnosis in the February 2020-October 2020 window. Similar hazard ratios were found on COVID-19 hospitalisation and across both study periods. CONCLUSIONS: In patients with osteoarthritis or back pain, we found no differential risks of incident COVID-19 diagnosis or COVID-19 hospitalisation for ibuprofen users compared with other ns-NSAIDs, COX-2i or paracetamol. Our findings support regulatory recommendations that NSAIDs, including ibuprofen, should be prescribed as indicated in the same way as before the COVID-19 pandemic, especially for those who rely on ibuprofen or NSAIDs to manage chronic arthritis or musculoskeletal pain symptoms.

Effect of nano-curcumin on various diseases: A comprehensive review of clinical trials.

The antioxidant, anti-inflammatory, and antibacterial properties of curcumin have made it a valuable herbal product for improving various disorders, such as COVID-19, cancer, depression, anxiety, osteoarthritis, migraine, and diabetes. Recent research has demonstrated that encapsulating curcumin in nanoparticles might improve its therapeutic effects and bioavailability. To our knowledge, the efficacy of nano-curcumin on different aspects of health and disease has not been summarized in a study. Therefore, this review aimed to evaluate nano-curcumin's efficacy in various diseases based on the findings of clinical trials. In order to review publications focusing on nanocurcumin's impact on various diseases, four databases were searched, including PubMed, Scopus, Web of Science, and Google Scholar. This review highlights the potential benefits of nano-curcumin in improving a wide range of human diseases including COVID-19, neurological disorders, chronic disease, oral diseases, osteoarthritis, metabolic syndrome, and other diseases, especially as an adjunct to standard therapy and a healthy lifestyle.

Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis.

BACKGROUND: The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation. METHODS: In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon. RESULTS: Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model. CONCLUSIONS: Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.

A tale of osteoarthritis among older adults during the COVID-19 pandemic in Bangladesh: A repeated cross-sectional study.

BACKGROUND: Due to restrictions in social gatherings imposed due to the COVID-19 pandemic, physical and other daily activities were limited among the older adults. The present study aimed to estimate the change in osteoarthritis prevalence among older adults during the COVID-19 pandemic in Bangladesh. METHODS: This repeated cross-sectional study was conducted through telephone interviews among older adults aged 60 years and above on two successive occasions (October 2020 and September 2021) during the COVID-19 pandemic in Bangladesh. The prevalence of osteoarthritis was measured by asking the participants if they had osteoarthritis or joint pain problems. RESULTS: A total of 2077 participants (1032 in 2020-survey and 1045 in 2021-survey) participated in the study. The prevalence of self-reported joint pains or osteoarthritis significantly increased from 45.3% in 2020 to 54.7% in 2021 (P = 0.006), with an increasing odd in the adjusted analysis (aOR 1.27, 95% CI 1.04-1.54). We also found that osteoarthritis prevalence significantly increased among the participants from the Chattogram and Mymensingh divisions, aged 60-69 years, males, married, rural residents, and living with a family. A significant increase was also documented among those who received formal schooling, had a family income of 5000-10000 BDT, resided with a large family, were unemployed or retired, and lived away from a health facility. CONCLUSIONS: Our study reported a significant increased prevalence of osteoarthritis among older adults from 2020 to 2021 during this pandemic in Bangladesh. This study highlights the need for the development and implementation of initiatives for the screening and management of osteoarthritis through a primary health care approach during any public health emergencies.

Patient Satisfaction and Interest in Telemedicine Visits Following Total Knee and Hip Replacement Surgery.

Introduction: Telemedicine is the practice of caring for patients remotely when the patient and provider are not physically present at the same location. Within orthopedic surgery, telemedicine offers care without the typical obstacles of an in-person appointment such as difficulty ambulating following surgery and patient wait times. In this study, we evaluated patient interest and satisfaction in postoperative telemedicine visits following hip or knee arthroplasty surgery. Materials and Methods: Patients were offered either a traditional in-person or a remote telemedicine postoperative visit following surgery. Patients were asked to complete a satisfaction survey following their postoperative visit regarding their experience. Patient-survey responses as well as patient-reported outcome metrics were captured using a mobile and web-based electronic patient rehabilitation application. Results: A total of 766 patients were included in this study with 360 offered postoperative telemedicine visits and 402 offered traditional in-person visits. Two hundred fifty-nine patients reported satisfaction levels with their telemedicine visit, with 58.3% of patients characterizing their feelings with the visit as "extremely satisfied," 32.0% as "satisfied," 8.9% as "neutral," 0.3% as "dissatisfied," and 0.3% as "extremely dissatisfied." A total of 713 patients reported how the COVID-19 pandemic effected their feelings toward telemedicine with 12.9% of patients characterizing the affect as "extremely positively," 33.1% of patients as "positively," 48.9% of patients as "neutral," 3.6% of patients as "negatively," and 1.4% of patients as "extremely negatively." There were no significant differences in the change between preoperative Hip disability and Osteoarthritis Outcome Scores/Knee Injury and Osteoarthritis Outcome Score Joint Replacement, or Veterans RAND 12 Physical and Mental components and these values at 12 weeks follow-up and 1-year follow-up, respectively, in patients who had telemedicine visits versus those who had traditional in-person visits. Discussion: The results of this study demonstrate that the patients who decided to have a telemedicine visit during their postoperative visit were satisfied with their experience. Overall, COVID-19 had a positive influence on patient's feelings toward telemedicine visits.

Surgery for Osteoarthritis: Total Joint Arthroplasty, Realistic Expectations of Rehabilitation and Surgical Outcomes: A Narrative Review.

This narrative review highlights the prevalence of osteoarthritis as a chronic disease that directly contributes to the ever-growing health care expenditure to treat this condition. The increasing demand of total joint arthroplasty globally is explained in conjunction with the importance of understanding candidate suitability for arthroplasty surgery in order to maximize surgical outcomes and self-reported patient satisfaction after the surgery. Rehabilitation care following total hip arthroplasty and total knee arthroplasty, particularly the inappropriate use of inpatient rehabilitation service, is also explained, in addition to the enhanced recovery after surgery.

Discovery of new senolytics using machine learning (preprint)

Cellular senescence is a stress response characterised by a permanent cell cycle arrest and a proinflammatory secretome. In addition to its tumour suppressor role, senescence is involved in ageing and promotes many disease processes such as cancer, type 2 diabetes, osteoarthritis, and SARS-CoV-2 infection. There is a growing interest in therapies based on targeted elimination of senescent cells, yet so far only a few such senolytics are known, partly due to the poor grasp of the molecular mechanisms that control the senescence survival programme. Here we report a highly effective machine learning pipeline for the discovery of senolytic compounds. Using solely published data, we trained machine learning algorithms to classify compounds according to their senolytic action. Models were trained on as few as 58 known senolytics against a background of FDA-approved compounds or in late-stage clinical development (2,523 in total). We computationally screened various chemical libraries and singled out top candidates for validation in human lung fibroblasts (IMR90) and lung adenocarcinoma (A549) cell lines. This led to the discovery of three novel senolytics: ginkgetin, oleandrin and periplocin, with potency comparable to current senolytics and a several hundred-fold reduction in experimental screening costs. Our work demonstrates that machine learning can take maximum advantage of existing drug screening data, paving the way for new open science approaches to drug discovery for senescence-associated diseases.

A predictive model for hospitalization and survival to COVID-19 in a retrospective population-based study (preprint)

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is highly transmissible and has been responsible for a pandemic associated with a high number of deaths. The clinical management of patients and the optimal use of resources are two important factors in reducing this mortality, especially in scenarios of high incidence. To this end, it is necessary to develop tools that allow early triage of patients with the minimal use of diagnostic tests and based on readily accessible data, such as electronic medical records. This work proposes the use of a machine learning model that allows the prediction of mortality and risk of hospitalization using simple demographic characteristics and comorbidities, using a COVID-19 dataset of 86867 patients. In addition, we developed a new method designed to deal with data imbalance problems. The model was able to predict with high accuracy (89-93%, ROC-AUC = 0.94) the patient's final status (expired/discharged) and with medium accuracy the risk of hospitalization (71-73%, ROC-AUC = 0.75). These models were obtained by assembling and using easily obtainable clinical characteristics (2 demographic characteristics and 19 predictors of comorbidities). The most relevant features of these models were the following patient characteristics: age, sex, number of comorbidities, osteoarthritis, obesity, depression, and renal failure.

Preoperative patients' health decrease moderately, while hospital costs increase for hip and knee replacement due to the first COVID-19 lockdown in Germany.

PURPOSE: The purpose of this study was a comparison between osteoarthritis patients with primary hip and knee replacements before, during and after the first COVID-19 lockdown in Germany. Patients' preoperative health status is assumed to decrease, owing to delayed surgeries. Costs for patients with osteoarthritis were assumed to increase, for example, due to higher prices for protective equipment. Hence, a comparison of patients treated before, during and after the first lockdown is conducted. METHODS: In total, 852 patients with primary hip or knee replacement were included from one hospital in Germany. Preoperative health status was measured with the WOMAC Score and the EQ-5D-5L. Hospital unit costs were calculated using a standardised cost calculation. Kruskal-Wallis tests and Chi-squared tests were applied for the statistical analyses. RESULTS: The mean of the preoperative WOMAC Score was slightly higher (p < 0.01) for patients before the first lockdown, compared with patients afterwards. Means of the EQ-5D-5L were not significantly different regarding the lockdown status (NS). Length of stay was significantly reduced by approximately 1 day (p < 0.001). Total inpatient hospital unit costs per patient and per day were significantly higher for patients during and after the first lockdown (p < 0.001). CONCLUSION: Preoperative health, measured with the WOMAC Score, worsened slightly for patients after the first lockdown compared with patients undergoing surgery before COVID-19. Preoperative health, measured using the EQ-5D-5L, was unaffected. Inpatient hospital unit costs increased significantly with the COVID-19 pandemic. LEVEL OF EVIDENCE: Retrospective cohort study, III.

Medical management of osteoarthritis during the CO-VID-19 pandemic: a challenge for the present and the future.

Abstract: The ongoing Covid-19 pandemic has inevitably changed the treatment of many chronic diseases which has been suspended or has suffered dangerous slowdowns. Osteoarthritis (OA) is the most common musculoskeletal disease. As a result, the medical management of Osteoarthritis was heavily impacted by the pandemic, and it required new therapeutic strategies. The purpose of this descriptive review is to provide an overview of how much the pandemic has affected the medical management of osteoarthritis and to outline a number of possible countermeasures. The COVID-19 pandemic requires a "multimodal approach": physicians are called to test the management of Osteoarthritis patients at a distance, through the tools made available by telemedicine, for all cases in which direct contact is avoidable. Therapies that instead require a direct intervention on the patient impose that all the procedures are carried out in complete safety, scrupulously keeping to the use of personal protective equipements.