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• W3119318774 abstract "We describe ten out of 52 patients with severe COVID-19 requiring prolonged mechanical ventilation who developed extensive heterotopic ossification (HO) around the shoulder, the elbow and the hip. Basic demographic characteristics, laboratory data, clinical presentation and treatment of acute respiratory distress syndrome (ARDS) were compared using the chi-squared test or Fisher's exact test for categorical variables, and the Mann–Whitney test for continuous variables. Odds ratios of developing HO were investigated using logistic regression models. Written informed consent was obtained from all patients. Between 29 February and 20 April 2020, 82 patients were admitted to our intensive care unit (ICU) because of ARDS due to SARS-CoV-2 infection requiring invasive mechanical ventilation. Of these, 52 patients had more than one computed tomography (CT) scan during the hospitalization and were included in the analysis. During the recovery period, five patients reported severe shoulder, elbow and hip pain with decreased joint mobility. CT performed at a median of 43 days (interquartile range (IQR) 35–48) after admission showed in these and in additional five asymptomatic patients extensive HO around the shoulder, the elbow and the hip, corresponding to a HO prevalence of 19.2%. Baseline characteristics according to HO are shown in Table 1. Most patients were males (8/10) and had at least one co-morbidity. The median age was 71 years (IQR 67–74). Treatment of severe ARDS consisted of mechanical ventilation during a median of 36 days (IQR 25–45) with prone positioning during 12 days (IQR 7–16) in 8/10, neuromuscular blockade in 9/10, and a 3-week course of steroids (mean dosage prednisone equivalent of 0.6 mg/kg/day) in 3/10 patients. On CT scans we observed either an asymmetric enlargement with inhomogeneous density and mild calcifications of the muscles (early phase) or more advanced calcifications (mineralization phase), mainly with a linear morphology. We observed an involvement of the muscles of the hip in seven cases, posteriorly and medially located (gluteus minimus, gemellus superior and inferior, quadratus femoris, piriformis and obturator internus muscles in six cases, four bilateral and two monolateral) and anteriorly located (ileo-psoas muscle in one case, monolateral); an involvement of the muscles of the shoulder in three cases, anteriorly located (subscapularis muscle in two cases, monolateral) and circumferentially located (rotator cuff, deltoid, biceps and triceps in one case, bilateral); and an involvement of the elbow in one case, posteromedially (medial head of the triceps, monolateral). One patient, showing HO in the elbow region, reported severe pain with immobility of the right arm that was refractory to conservative treatment. In this patient, surgical intervention with neurolysis and transposition of the right ulnar nerve was needed. No vascular compression was observed.Table 1Characteristics of 52 patients with severe COVID-19 and ARDS requiring mechanical ventilation according to the development of heterotopic ossificationCharacteristicHeterotopic ossificationN = 10No heterotopic ossificationN = 42pn%n%Age (median, IQR)7167–746960–730.530Male gender88034810.945Body mass index, kg/m2 (median, IQR)31.924.4–3427.725.7–30.80.174Arterial hypertension7702661.90.633Type 2 diabetes mellitus33013310.953Cardiovascular disease4401126.20.308Duration of mechanical ventilation, days (median, IQR)3625–45227–36<0.001Prone positioning99032760.477Time of prone positioning, days (median, IQR)127–1654–120.105Steroids for ARDS treatment66020470.479Minimal lymphocyte count, × 109/μL (median, IQR)0.660.62–0.730.570.43–0.790.093Maximal C-reactive protein, mg/L (median, IQR)352331–377392304–4810.673Maximal creatine kinase, U/L (median, IQR)820262–1114295154–5070.037Minimal ionized calcium, mmol/L (median, IQR)0.970.92–1.020.930.90–1.040.834Ventilator-associated pneumonia9902866.70.102Catheter-related blood stream infection6602252.40.470Duration of hospitalization (days) (median, IQR)5343–583324–420.002IQR, interquartile range. Open table in a new tab IQR, interquartile range. In a multivariate analysis, HO was associated with longer mechanical ventilation (odds ratio (OR) 2.64 for each additional week, 95% confidence interval (CI) 1.26–5.51, p 0.009) and longer hospitalization (OR 2.1 for each additional week, 95% CI 1.3–3.4, p 0.004), suggesting that prolonged immobilization might have played a crucial role in the occurrence of HO. We also observed a trend towards higher maximal creatine kinase values in patients who developed HO (OR 1.22 for each creatin kinase (CK) increase of 100 U/L, 95% CI 1.01–1.47, p 0.043). Heterotopic ossification, the formation of bone outside the skeletal system, is a rare but potentially debilitating condition, usually associated with paralysis and immobilization following trauma, neurologic injury, ARDS, surgery and burn [[1]Sugita A. Hashimoto J. Maeda A. Kobayashi J. Hirao M. Masuhara K. et al.Heterotopic ossification in bilateral knee and hip joints after long-term sedation.J Bone Mineral Metab. 2005; 23: 329-332Crossref PubMed Scopus (12) Google Scholar,[2]McCarthy E.F. Sundaram M. Heterotopic ossification: a review.Skeletal Radiol. 2005; 34: 609-619Crossref PubMed Scopus (292) Google Scholar]. The pathogenesis is still unclear, possibly resulting from an imbalance between certain neuro-humoral factors, calcium homeostasis, autonomic dysregulation, micro-bleedings, osteoporosis and muscle atrophy [[2]McCarthy E.F. Sundaram M. Heterotopic ossification: a review.Skeletal Radiol. 2005; 34: 609-619Crossref PubMed Scopus (292) Google Scholar,[3]Kaplan F.E. Glaser D.L. Hebela N. Shore E.M. Heterotopic ossification.J Am Acad Orthop Surg. 2004; 12: 116-125Crossref PubMed Scopus (289) Google Scholar]. The main complications of HO are functional impairment of the involved anatomic districts and peripheral nerve entrapment [[4]Hudson S.J. Brett S.J. Heterotopic ossification – a long-term consequence of prolonged immobility.Crit Care. 2006; 10: 174Crossref PubMed Scopus (20) Google Scholar,[5]Herridge M.S. Cheung A.M. Tansey C.M. Matte-Martyn A. Diaz-Granados N. Al-Saidi F. et al.One-year outcomes in survivors of the acute respiratory distress syndrome.N Engl J Med. 2003; 348: 683-693Crossref PubMed Scopus (1727) Google Scholar]. The prevalence of HO in our population was about fourfold higher than that reported in patients with ARDS (5%) [[5]Herridge M.S. Cheung A.M. Tansey C.M. Matte-Martyn A. Diaz-Granados N. Al-Saidi F. et al.One-year outcomes in survivors of the acute respiratory distress syndrome.N Engl J Med. 2003; 348: 683-693Crossref PubMed Scopus (1727) Google Scholar]. We assume that prolonged immobilization as a result of longer sedation and neuromuscular blockade for severe ARDS has played a decisive role for HO in our patients. However, it is plausible that other factors, such as the deranged calcium metabolism, systemic inflammatory condition and local myositis, possibly due to the SARS-CoV-2 virus, might have contributed to the higher prevalence of HO. Clinicians should be aware of this debilitating complication in critically ill patients with severe COVID-19, particularly if severe muscular and articular pain arise in the recovery period. We recommend early passive mobilization during ICU stay to prevent HO in patients with COVID-19. The authors declare that they have no conflicts of interest and no external funding related to this study. E.S., L.E., A.F.C. conceived and designed the study. L.E. performed statistical analysis. E.S., L.E., R.G., C.P. and A.F.C. collected patients' data. All authors interpreted the data and wrote the manuscript. All authors read and approved the final manuscript. -Micol Pallanza, MD, Division of Infectious Diseases, Ospedale San Giovanni, Bellinzona, Switzerland.-Barbara Lucchini, MD, Department of Internal Medicine, Ospedale La Carita, Locarno, Switzerland.-Luca Sardella, MD, Division of Pneumology, Ospedale San Giovanni, Bellinzona, Switzerland.-Mauro Natale Molina, MD, Department of Surgery and Orthopedics, Ospedale La Carità, Locarno, Switzerland. Re: “High prevalence of heterotopic ossification in critically ill patients with severe COVID-19” by Stoira et al.Clinical Microbiology and InfectionVol. 27Issue 7PreviewWe would like to respond to the Letter to the Editor sent by Stoira et al. “High prevalence of heterotopic ossification in critically ill patients with severe COVID-19” to give the point of view of an experienced medico-surgical team in charge of neurogenic heterotopic ossification (HO) case management [1]. Full-Text PDF Open Archive‘High prevalence of heterotopic ossification in critically ill patients with severe COVID-19’ – Author's replyClinical Microbiology and InfectionVol. 27Issue 7PreviewWe are grateful for the thoughtful comments by de l’Escalopier et al. [1] and appreciate the opportunity to respond. Full-Text PDF Open Archive" @default.
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• W3119318774 title "High prevalence of heterotopic ossification in critically ill patients with severe COVID-19" @default.
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