Rationale: Diaphragmatic insults occurring during intensive care unit (ICU) stays have become the focus of intense research. However, diaphragmatic abnormalities at the initial phase of critical illness remain poorly documented in humans. Objectives: To determine the incidence, risk factors, and prognostic impact of diaphragmatic impairment on ICU admission. Methods: Prospective, 6-month, observational cohort study in two ICUs. Mechanically ventilated patients were studied within 24 hours after intubation (Day 1) and 48 hours later (Day 3). Seventeen anesthetized intubated control anesthesia patients were also studied. The diaphragm was assessed by twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Measurements and Main Results: Eighty-five consecutive patients aged 62 (54–75) (median [interquartile range]) were evaluated (medical admission, 79%; Simplified Acute Physiology Score II, 54 [44–68]). On Day 1, Ptr,stim was 8.2 (5.9–12.3) cm H2O and 64% of patients had Ptr,stim less than 11 cm H2O. Independent predictors of low Ptr,stim were sepsis (linear regression coefficient, −3.74; standard error, 1.16; P = 0.002) and Simplified Acute Physiology Score II (linear regression coefficient, −0.07; standard error, 1.69; P = 0.03). Compared with nonsurvivors, ICU survivors had higher Ptr,stim (9.7 [6.3–13.8] vs. 7.3 [5.5–9.7] cm H2O; P = 0.004). This was also true for hospital survivors versus nonsurvivors (9.7 [6.3–13.5] vs. 7.8 [5.5–10.1] cm H2O; P = 0.004). Day 1 and Day 3 Ptr,stim were similar. Conclusions: A reduced capacity of the diaphragm to produce inspiratory pressure (diaphragm dysfunction) is frequent on ICU admission. It is associated with sepsis and disease severity, suggesting that it may represent another form of organ failure. It is associated with a poor prognosis. Clinical trial registered with www.clinicaltrials.gov (NCT 00786526).

Intensive care unit (ICU)-acquired weakness and diaphragm dysfunction are frequent conditions, both associated with poor prognosis in critically ill patients. While it is well established that ICU-acquired weakness severely impairs long-term prognosis, the association of diaphragm dysfunction with this outcome has never been reported. This study investigated whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and ICU-acquired weakness has a particular association with 2-year survival and health-related quality of life (HRQOL). This study is an ancillary study derived from an observational cohort study. Patients under mechanical ventilation were enrolled at the time of their first spontaneous breathing trial. Diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation < 11 cmH2O and ICU-acquired weakness was defined by Medical Research Council (MRC) score < 48. HRQOL was evaluated with the SF-36 questionnaire. Sixty-nine of the 76 patients enrolled in the original study were included in the survival analysis and 40 were interviewed. Overall 2-year survival was 67% (46/69): 64% (29/45) in patients with diaphragm dysfunction, 71% (17/24) in patients without diaphragm dysfunction, 46% (11/24) in patients with ICU-acquired weakness and 76% (34/45) in patients without ICU-acquired weakness. Patients with concomitant diaphragm dysfunction and ICU-acquired weakness had a poorer outcome with a 2-year survival rate of 36% (5/14) compared to patients without diaphragm function and ICU-acquired weakness [79% (11/14) (p < 0.01)]. Health-related quality of life was not influenced by the presence of ICU-acquired weakness, diaphragm dysfunction or their coexistence. ICU-acquired weakness but not diaphragm dysfunction was associated with a poor 2-year survival of critically ill patients.

Immune-checkpoint-inhibitor (ICI)–associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and are highly fatal. We report the results of a strategy that included identification of individuals with severe ICI myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with the CTLA4 fusion protein abatacept and the JAK inhibitor ruxolitinib. Forty cases with definite ICI myocarditis were included with pathologic confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. The abatacept dose was adjusted using CD86 receptor occupancy on circulating monocytes. The myotoxicity-related fatality rate was 3.4% (1/30) in these 30 patients versus 60% in the first quartile (P < 0.0001). These clinical results are hypothesis-generating and need further evaluation. Significance: Early management of respiratory muscle failure using mechanical ventilation and high-dose abatacept with CD86 receptor occupancy monitoring combined with ruxolitinib may be promising to mitigate high fatality rates in severe ICI myocarditis. See related commentary by Dougan, p. 1040. This article is highlighted in the In This Issue feature, p. 1027

Background This study provides a detailed imaging assessment in a large series of COVID-19 patients with neurological manifestations. Purpose To review the MRI findings associated with acute neurol...