Rationale: Nearly 60% of patients who are intubated in intensive care units (ICUs) experience dysphagia after extubation, and approximately 50% of them aspirate. Little is known about dysphagia recovery time after patients are discharged from the hospital.Objectives: To determine factors associated with recovery from dysphagia symptoms after hospital discharge for acute respiratory distress syndrome (ARDS) survivors who received oral intubation with mechanical ventilation.Methods: This is a prospective, 5-year longitudinal cohort study involving 13 ICUs at four teaching hospitals in Baltimore, Maryland. The Sydney Swallowing Questionnaire (SSQ), a 17-item visual analog scale (range, 0-1,700), was used to quantify patient-perceived dysphagia symptoms at hospital discharge, and at 3, 6, 12, 24, 36, 48, and 60 months after ARDS. An SSQ score greater than or equal to 200 was used to indicate clinically important dysphagia symptoms at the time of hospital discharge. Recovery was defined as an SSQ score less than 200, with a decrease from hospital discharge greater than or equal to 119, the reliable change index for SSQ score. Fine and Gray proportional subdistribution hazards regression analysis was used to evaluate patient and ICU variables associated with time to recovery accounting for the competing risk of death.Measurements and Main Results: Thirty-seven (32%) of 115 patients had an SSQ score greater than or equal to 200 at hospital discharge; 3 died before recovery. All 34 remaining survivors recovered from dysphagia symptoms by 5-year follow-up, 7 (23%) after 6 months. ICU length of stay was independently associated with time to recovery, with a hazard ratio (95% confidence interval) of 0.96 (0.93-1.00) per day. Conclusions:One-third of orally intubated ARDS survivors have dysphagia symptoms that persist beyond hospital discharge. Patients with a longer ICU length of stay have slower recovery from dysphagia symptoms and should be carefully considered for swallowing assessment to help prevent complications related to dysphagia.

Over the follow-up period, the majority of ARDS survivors experienced a physical decline, with older age and pre-ICU comorbidity being important risk factors for this decline.

Objective To longitudinally evaluate the association of post-ICU muscle weakness and associated trajectories of weakness over time with 5-year survival. Design Longitudinal prospective cohort study over 5 years of follow-up Patients 156 acute respiratory distress syndrome (ARDS) survivors Setting 13 ICUs in 4 hospitals in Baltimore, MD Interventions None Measurements and Main Results Strength was evaluated with standardized manual muscle testing using the Medical Research Council sumscore (range: 0–60, higher is better), with post-ICU weakness defined as sumscore <48. Muscle strength was assessed at hospital discharge and at 3, 6, 12, 24, 36, and 48 months after ARDS. At discharge, 38% of patients had muscle weakness. Every 1 point increase in sumscore at discharge was associated with improved survival (hazard ratio (95% confidence interval) 0.96 (0.94–0.98)), with similar findings longitudinally (0.95, 0.93–0.98). Having weakness at discharge was associated with worse 5-year survival (1.75, 1.01–3.03); but the association was attenuated (1.54, 0.82–2.89) when evaluated longitudinally over follow-up. Occurring in 50% of patients during follow-up, persisting and resolving trajectories of muscle weakness were associated with worse survival (3.01, 1.12–8.04; and 3.14, 1.40–7.03, respectively) compared to a trajectory of maintaining no muscle weakness. Conclusions At hospital discharge, >1/3 of ARDS survivors had muscle weakness. Greater strength at discharge and throughout follow-up was associated with improved 5-year survival. In patients with post-ICU weakness, both persisting and resolving trajectories, were commonly experienced and associated with worse survival during follow-up.

Across 5-year follow-up, nearly one-third of previously employed ARDS survivors never returned to work. Delayed return to work was associated with patient-related and intensive care unit/hospital-related factors, substantial lost earnings and a marked rise in government-funded healthcare coverage. These important consequences emphasise the need to design and evaluate vocation-based interventions to assist ARDS survivors return to work.

Background CD19-directed CAR T-cell therapy (CAR-T) has emerged as an effective therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL). The neurologic toxicity seen with CAR-T, referred to as Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), is poorly understood. To better elucidate the clinical characteristics, treatment outcomes, and correlative biomarkers of ICANS, we review here a single-center analysis of ICANS after CAR-T therapy in R/R LBCL. Methods Patients (n=45) with R/R LBCL treated with axicabtagene ciloleucel (axi-cel) were identified. Data regarding treatment course, clinical outcomes, and correlative studies were collected. Patients were monitored and graded for ICANS via CARTOX-10 scoring and CTCAE v4.03 criteria, respectively. Results Twenty-five (56%) patients developed ICANS, eighteen (72%) of which had severe (grade 3-4) ICANS. Median time to development of ICANS of 5 days (range 3-11). Elevated pre-infusion (D0) fibrinogen (517 vs. 403 mg/dL, ULN 438mg/dL, p=0.01) and D0 LDH (618 vs. 506 units/L, ULN 618 units/L, p=0.04) were associated with ICANS. A larger drop in fibrinogen was associated with ICANS (393 vs 200, p&lt;0.01). Development of ICANS of any grade had no effect on complete remission (CR), progression-free survival (PFS) or overall survival (OS). Duration and total dose of steroid treatment administered for ICANS did not influence CR, PFS, or OS. Conclusions ICANS after CAR-T with axi-cel for R/R LBCL was seen in about half of patients, majority of which was high grade. Contrary to previous reports, neither development of ICANS nor its treatment were associated with inferior CR, PFS, or OS. The novel finding of high D0 fibrinogen level can identify patients at higher risk for ICANS.