The novel coronavirus disease 2019 (COVID-19) pandemic is a global crisis, challenging healthcare systems worldwide. Many patients present with a remarkable disconnect in rest between profound hypoxemia yet without proportional signs of respiratory distress (i.e. happy hypoxemia) and rapid deterioration can occur. This particular clinical presentation in COVID-19 patients contrasts with the experience of physicians usually treating critically ill patients in respiratory failure and ensuring timely referral to the intensive care unit can, therefore, be challenging. A thorough understanding of the pathophysiological determinants of respiratory drive and hypoxemia may promote a more complete comprehension of a patient's clinical presentation and management. Preserved oxygen saturation despite low partial pressure of oxygen in arterial blood samples occur, due to leftward shift of the oxyhemoglobin dissociation curve induced by hypoxemia-driven hyperventilation as well as possible direct viral interactions with hemoglobin. Ventilation-perfusion mismatch, ranging from shunts to alveolar dead space ventilation, is the central hallmark and offers various therapeutic targets.

Purposes The focus in the evaluation of total knee arthroplasty has shifted from objective measures of implant position and knee function, to patient-reported outcome measures (PROMs). The relation between these two measures was investigated and the possibility of prediction of the patient satisfaction level was evaluated by defining thresholds for improvement of (1) range of motion (ROM), (2) 6-min walk test (6MWT), (3) sit-to-stand test (STS) and (4) quadriceps force after TKA? Methods Fifty-seven patients were prospectively tested at preoperative and 6 months postoperative intervals. The ROM, 6MWT, STS-test and quadriceps force were evaluated. Two clusters were created based on the postoperative KOOS, OKS and the satisfaction subscore of the new KSS, cluster 1 consisted of patients with good to excellent PROMs, cluster 2 of patients with poorer PROMs. Patients in each cluster were more similar to each other than to those in the other cluster. Receiver operating characteristic (ROC)-curve analysis was used to identify thresholds for the functional outcomes that established cluster allocation. Multiple logistic regression was used to define a model to predict cluster allocation. Results Patients with high postoperative PROMs (cluster 1 allocation) showed higher postoperative functional outcomes (p < 0.05). Thresholds for the improvement of ROM (≥ 5°, OR 6.3, 95% CI 1.23-31.84), 6MWT (≥ 50 m, OR 8.2, 95% CI 1.61-42.18) STS (≥ 1.05 s, OR 3, 95% CI 0.56-16.07) and normalized Q4 force (≥ 1.5 N/BMI, OR 2.5, 95% CI 0.49-12.89) were found to be predictors of cluster allocation. A model to predict the cluster allocation contained gender, ROM improvement and 6MWT improvement (sensitivity 91.1%, specificity 75%). Conclusions Thresholds for improvement of functional parameters can predict the patient satisfaction cluster. Patients, who are male, improve on the 6-min walk test with 50 m or more and have an increased range of motion of 5° or more, compared to the preoperative situation, are 6-8 times more likely of being satisfied after TKA. These tests are easy to use in clinical practice and can predict the level of patient satisfaction after TKA. Level of evidence Level II, prognostic study.

In their letter-to-the-editor entitled “Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19”, Tobin et al. (Respir Res 21:249, 2020) debated our views on happy hypoxemia in COVID-19 (Respir Res 21:198, 2020). We thank the authors for their interesting comments and alternative viewpoints, and we would like to clarify several important aspects raised.

The coronavirus disease 2019 (COVID-19) pandemic is challenging health care systems worldwide. People with myotonic dystrophy type 1 (DM1) represent a high-risk population during infectious disease outbreaks, little is known about the potential impact of COVID-19 on patients with DM1. We studied the clinical course of COVID-19 in three hospitalized patients with myotonic dystrophy type 1 or Steinert's disease, between April 1, 2020-April 30-2020. All three had advanced Steinert's disease receiving non-invasive nocturnal home ventilatory support. Two of them lived in a residential care centre. Two patients had a limited respiratory capacity, whereas one patient had a rather preserved functional capacity but more comorbidities. Two out of three patients were obese, none of them had diabetes mellitus. Two patients received hydroxychloroquine. Despite maximal supportive care with oxygen therapy, antibiotics, intensive respiratory physiotherapy and noninvasive positive pressure ventilation, all three patients eventually died due to COVID-19. Our case series of three patients with DM1 admitted for COVID-19 confirms that they are at high risk for severe disease and poor outcome. Clinical trials are needed to define best practices and determinants of outcomes in this unique population.

Background: Early risk stratification is crucial in critically ill COVID-19 patients. Myocardial injury is associated with worse outcome. This study aimed to evaluate cardiac biomarkers and echocardiographic findings in critically ill COVID-19 patients and to assess their association with 30-day mortality in comparison to other biomarkers, risk factors and clinical severity scores.Methods: Prospective, single-center, cohort study in patients with PCR-confirmed, critical COVID-19. Laboratory assessment included high sensitive troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission to ICU: a hs-cTnT ≥ 14 pg/mL and a NT-proBNP ≥ 450 pg/mL were considered as elevated. Transthoracic echocardiographic evaluation was performed within the first 48 h of ICU admission. The primary outcome was 30-day all-cause mortality. Predictive markers for mortality were assessed by ROC analysis and cut-off values by the Youden Index.Results: A total of 100 patients were included. The median age was 63.5 years, the population was predominantly male (66%). At the time of ICU admission, 47% of patients had elevated hs-cTnT and 39% had elevated NT-proBNP. Left ventricular ejection fraction was below 50% in 19.1%. Elevated cardiac biomarkers (hs-cTnT P-value &lt; 0.001, NT-proBNP P-value = 0.001) and impaired left ventricular function (P-value = 0.011) were significantly associated with mortality, while other biomarkers (D-dimer, ferritin, C-reactive protein) and clinical scores (SOFA) did not differ significantly between survivors and non-survivors. An optimal cut-off value to predict increased risk for 30-day all-cause mortality was 16.5 pg/mL for hs-cTnT (OR 8.5, 95% CI: 2.9, 25.0) and 415.5 pg/ml for NT-proBNP (OR 5.1, 95% CI: 1.8, 14.7).Conclusion: Myocardial injury in COVID-19 is common. Early detection of elevated hs-cTnT and NT-proBNP are predictive for 30-day mortality in patients with critical COVID-19. These markers outperform other routinely used biomarkers, as well as clinical indices of disease severity in ICU. The additive value of routine transthoracic echocardiography is disputable and should only be considered if it is likely to impact therapeutic management.

AimsAcetazolamide, an inhibitor of proximal tubular sodium reabsorption, leads to more effective decongestion in acute heart failure (AHF). It is unknown whether acetazolamide alters serum sodium and potassium levels on top of loop diuretics and if baseline values modify the treatment effect of acetazolamide.Methods and resultsThis is a pre‐specified sub‐analysis of the ADVOR trial that randomized 519 patients with AHF and volume overload in a 1:1 ratio to intravenous acetazolamide or matching placebo on top of standardized intravenous loop diuretics. Mean potassium and sodium levels at randomization were 4.2 ± 0.6 and 139 ± 4 mmol/L in the acetazolamide arm versus 4.2 ± 0.6 and 140 ± 4 mmol/L in the placebo arm. Hypokalaemia (<3.5 mmol/L) on admission was present in 44 (9%) patients and hyponatraemia (≤135 mmol/L) in 82 (16%) patients. After 3 days of treatment, 44 (17%) patients in the acetazolamide arm and 35 (14%) patients in the placebo arm developed hyponatraemia (p = 0.255). Patients randomized to acetazolamide demonstrated a slight decrease in mean potassium levels during decongestion, which was non‐significant over time (p = 0.053) and had no significant impact on hypokalaemia incidence (p = 0.061). Severe hypokalaemia (<3.0 mmol/L) occurred in only 7 (1%) patients, similarly distributed between the two treatment arms (p = 0.676). Randomization towards acetazolamide improved decongestive response irrespective of baseline serum sodium and potassium levels.ConclusionsAcetazolamide on top of standardized loop diuretic therapy does not lead to clinically important hypokalaemia or hyponatraemia and improves decongestion over the entire range of baseline serum potassium and sodium levels.

Pulmonary hypertension (PH) is present in an important proportion of patients with interstitial lung diseases (ILDs), encompassing a large, heterogeneous group of diffuse parenchymal lung diseases. Development of ILD-related PH is associated with reduced exercise capacity, increased need for supplemental oxygen, decreased quality of life and earlier death. Diagnosis of ILD-related PH is important and requires a high index of suspicion. Noninvasive diagnostic assessment can suggest the presence of PH, although right heart catheterization remains the gold standard to confirm the diagnosis and to assess its severity. A comprehensive assessment is needed to make sure reversible causes of PH have been ruled out, including thromboembolic events, untreated hypoxemia and sleep disordered breathing. The results of trials concerning pulmonary vasodilators in this particular patient group have been disappointing and, in some cases, were even associated with an increased risk of harm. Newer strategies such as medications administered through inhalation and combinations with antifibrotic drugs show encouraging results. Moreover, unraveling the role of the vasculature in the pathophysiology of pulmonary fibrosis and ILD-related PH may potentially unlock new therapeutic opportunities.

Background Early risk stratification is crucial in critically ill COVID-19 patients. Myocardial injury is associated with worse outcome. This study aimed to evaluate cardiac biomarkers and echocardiographic findings in critically ill COVID-19 patients and to assess their association with 30-day mortality in comparison to other biomarkers, risk factors and clinical severity scores.Methods Prospective, single-center, cohort study in patients with PCR-confirmed, critical COVID-19. Laboratory assessment included high sensitive troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission to ICU: a hs-cTnT ≥ 14 pg/mL and a NT-proBNP ≥ 450 pg/mL were considered as elevated. Transthoracic echocardiographic evaluation was performed within the first 48 hours of ICU admission. The primary outcome was 30-day all-cause mortality. Predictive markers for mortality were assessed by ROC analysis and cut-off values by the Youden Index.Results A total of 100 patients were included. The median age was 63.5 years, the population was predominantly male (66%). At the time of ICU admission, 47% of patients had elevated hs-cTnT and 39% had elevated NT-proBNP. Left ventricular ejection fraction was below 50% in 19.1%. Elevated cardiac biomarkers (hs-cTnT P-value < 0.001, NT-proBNP P-value = 0.001) and impaired left ventricular function (P-value 0.011) were significantly associated with mortality, while other biomarkers (D-dimers, ferritin, C-reactive protein) and clinical scores (SOFA) did not differ significantly between survivors and non-survivors. An optimal cut-off value to predict increased risk for 30-day all-cause mortality was 16.5 pg/mL for hs-cTnT (OR 8.5, 95% CI: 2.9, 25.0) and 415.5 pg/ml for NT-proBNP (OR 5.1, 95% CI: 1.8, 14.7).Conclusion Myocardial injury in COVID-19 is common. Early detection of elevated hs-cTnT and NT-proBNP are predictive for 30-day mortality in patients with critical COVID-19. These markers outperform other routinely used biomarkers, as well as clinical indices of disease severity in ICU. The additive value of routine transthoracic echocardiography is disputable and should only be considered if it is likely to impact therapeutic management.