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Introduction Narcolepsy is a disorder of sleep characterized by pathologic daytime sleepiness classically divided into two major subtypes – those with or without cataplexy. The underlying pathophysiologic mechanism is thought to be related to hypocretin/orexin; pathologically low levels of hypocretin characterize narcolepsy with cataplexy. We present a complex case of weakness in a patient evaluated for narcolepsy. Report of case(s) A 38 year-old male with a BMI of 33 presented with a decade of daytime sleepiness and sudden debilitating attacks of muscle weakness. He underwent level III home sleep testing revealing a respiratory event index of 5.3/h. After an unsuccessful trial of mandibular advancement, he was started on positive airways pressure (PAP) but continued to experience daytime sleepiness and episodes concerning for cataplexy including sensation of legs feeling stiff and falling with stress. He also described episodes of weakness while swimming with inability to stand or stabilize, prompting evaluation for narcolepsy with cataplexy. Sleep diary showed average nightly sleep of 6.5 hours, low sleep latency, and refreshing napping. He underwent PSG while using CPAP 8 cm H2O showing AHI 0.2/h, sleep time 6.2 hours, sleep latency 5.5 minutes and REM latency 33 minutes with evidence of REM sleep without atonia. He underwent MSLT showing a mean sleep latency of 7.6 minutes and 3/5 REM sleep onset periods. Therapeutic trials of venlafaxine and pitolisant did not result in symptomatic improvement, and further genetic testing with HLA DQB-1 was negative. CSF hypocretin measurement was normal (329 pg/mL, reference > 200 pg/mL). These effectively ruled out cataplexy as the cause of his weakness. He continued on PAP therapy, venlafaxine, and modafinil 200 mg for hypersomnia/narcolepsy without cataplexy with good response. Conclusion We present a complex case highlighting the utility of HLA and confirmatory CSF testing in the evaluation of cataplexy with episodes of acute weakness accompanying stress and strong emotion, with particularly dangerous events during swimming. Due to lack of therapeutic response despite positive MSLT, further testing with HLA and CSF hypocretin were pursued. This case highlights the limitations of history alone in the diagnosis of cataplexy, and the utility of advanced testing. Support (if any)

Background: Survivors of COVID-19 pneumonia often suffer from chronic critical illness (CCI) and require long-term hospitalization. Long-term acute care (LTAC) hospitals are vital in the care of CCI patients, but their role for patients post COVID-19 infection is not known. Barlow Respiratory Hospital (BRH) is a 105-bed, LTAC hospital network serving ventilator-dependent and medically-complex patients transferred from the ICUs of hospitals in southern California. We report patient characteristics of our first series of COVID-19 survivors admitted to the post-acute venue of an LTAC hospital. Methods: Single-center observational descriptive report of patients recovering from acute infectious complications of COVID-19 pneumonia requiring long-term respiratory support. Results: From 28 April to 7 September 2020, 41 patients were admitted to BRH for continued recovery from COVID-19 pneumonia. Median age: 68 [44-94] years, 25/41 (61%) male, 33/41 (80.5%) with tracheostomy, 21/41 (51.2%) on invasive mechanical ventilation, 9/41 (22%) receiving hemodialysis. All mechanical ventilation and hemodialysis interventions were initiated at the transferring hospital. Conclusions: To our knowledge, this is the first report to characterize CCI and medically complex COVID-19 patients transferred to the post-acute venue of an LTAC hospital. Patients on average spent over six weeks in the transferring hospital mostly in the ICU, are largely elderly, carry the known risk factors for COVID-19 infection, and experienced respiratory failure necessitating prolonged mechanical ventilation via tracheostomy. Our findings suggest that these patients will continue to require considerable medical interventions and treatments, including weaning from mechanical ventilation, owing to the numerous sequelae of the infection and the burden of acute-on-chronic diseases. As ICU survival rates improve, this research further emphasizes the important role of the LTAC hospital in responding to the COVID-19 crisis.

Background Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury commonly associated with pneumonia, including coronavirus disease-19 (COVID-19). The resultant effect can be persistent lung damage, but its extent is not known. We used quantitative high resolution computed tomography (QHR-CT) lung scans to radiographically characterize the lung damage in COVID-19 ARDS (CARDS) survivors. Methods Patients with CARDS (N=20) underwent QHR-CT lung scans 60 to 90 days after initial diagnosis, while hospitalized at a long-term acute care hospital (LTACH). QHR-CT assessed for mixed disease (QMD), ground glass opacities (QGGO), consolidation (QCON) and normal lung tissue (QNL). QMD was correlated with respiratory support on admission, tracheostomy decannulation and supplementary oxygen need on discharge. Results Sixteen patients arrived with tracheostomy requiring invasive mechanical ventilation. Four patients arrived on nasal oxygen support. Of the patients included in this study 10 had the tracheostomy cannula removed, four remained on invasive ventilation, and two died. QHR-CT showed 45% QMD, 28.1% QGGO, 3.0% QCON and QNL=23.9%. Patients with mandatory mechanical ventilation had the highest proportion of QMD when compared to no mechanical ventilation. There was no correlation between QMD and tracheostomy decannulation or need for supplementary oxygen at discharge. Conclusions Our data shows severe ongoing lung injury in patients with CARDS, beyond what is usually expected in ARDS. In this severely ill population, the extent of mixed disease correlates with mechanical ventilation, signaling formation of interstitial lung disease. QHR-CT analysis can be useful in the post-acute setting to evaluate for interstitial changes in ARDS.

Obesity-related adipose inflammation has been thought to be a causal factor for the development of insulin resistance and type 2 diabetes. Infiltrated macrophages in adipose tissue of obese animals and humans are an important source for inflammatory cytokines. Clodronate liposomes can ablate macrophages by inducing apoptosis. In this study, we aim to determine whether peritoneal injection of clodronate liposomes has any beneficial effect on systemic glucose homeostasis/insulin sensitivity and whether macrophage content in visceral adipose tissue will be reduced in diet-induced obese (DIO) mice. Clodronate liposomes were used to deplete macrophages in lean and DIO mice. Macrophage content in visceral adipose tissue, metabolic parameters, glucose and insulin tolerance, adipose and liver histology, adipokine and cytokine production were examined. Hyperinsulinemic-euglycemic clamp study was also performed to assess systemic insulin sensitivity. Peritoneal injection of clodronate liposomes significantly reduced blood glucose and insulin levels in DIO mice. Systemic glucose tolerance and insulin sensitivity were mildly improved in both lean and DIO mice treated with clodronate liposomes by intraperitoneal (i.p.) injection. Hepatosteatosis was dramatically alleviated and suppression of hepatic glucose output was markedly increased in DIO mice treated with clodronate liposomes. Macrophage content in visceral adipose tissue of DIO mice was effectively decreased without affecting subcutaneous adipose tissue. Interestingly, levels of insulin sensitizing hormone adiponectin, including the high molecular weight form, were significantly elevated in circulation. Intraperitoneal injection of clodronate liposomes reduces visceral adipose tissue macrophages, improves systemic glucose homeostasis and insulin sensitivity in DIO mice, which can be partially attributable to increased adiponectin levels.

Liberation from prolonged mechanical ventilation is challenging and its outcomes are poor. Patients who failed at least three spontaneous breathing trials, often referred to as prolonged weaning patients, are usually weaned with protocolized programs in specialized weaning units, but there are no standardized strategies to facilitate their ventilator liberation. The objective of this study was to compare the ventilator liberation rate of two common ventilator weaning programs. Tracheostomized patients with ongoing invasive mechanical ventilation for at least 21 day who were admitted to Barlow Respiratory Hospital for ventilator weaning were studied. Patients who passed spontaneous breathing trial on admission were excluded. In a prospective parallel group, non-blinded clinical study, patients were randomized to receive either the Pressure Support Ventilation (PSV) weaning program or the Therapist-Implemented Patient-Specific (TIPS) weaning program. Randomization was performed using a computer algorithm of block design. The primary outcome was ventilator liberation success. The secondary outcomes were hospital length of stay, physical recovery, discharge disposition and mortality. Significant hospital events were also compared between the groups. N = 25 patients were studied in PSV and N = 26 in the TIPS group. Outcomes were reported for all patients. The liberation success rate at 30 days was 37.5% (standard error, SE = 9.9%) in the PSV and 46.2% (SE = 9.8%) in the TIPS group (p = 0.58, odds ratio, OR 1.42, RD 8.7%, 95% confidence interval, CI=-18.6-35.9). The liberation rate at discharge was 44% (SE = 9.9%) in the PSV group and 53.8% (SE = 9.8%) in the TIPS group (p = 0.54, OR:1.48, RD 9.8%, CI=-17.2-37.2%). The inpatient mortality was: PSV = 24% (SE 8.5%) and TIPS = 11.5% (SE 6.3%), p = 0.291, OR 0.413, RD=-12.5%, CI=-33.2-8.3%. We did not find a significant difference between the two ventilator weaning programs in any of our outcomes, but our study describes a very sick patient population. Continued weaning beyond 30 days had improved liberation success. Both weaning paths are equally beneficial for prolonged mechanical ventilation patients who undergo prolonged weaning. The trial was registered retroactively at ClinicalTrials.gov, NCT06976554.

Introduction Chronic hypercapnia results from destruction of lung parenchyma which occurs in chronic lung diseases including interstitial lung disease (ILD), bronchiectasis, and chronic lung transplant rejection. Many patients with these diseases will experience progressive respiratory failure eventually requiring consideration of transplantation or re-transplantation. Due to physiologic changes in sleep including reduction in tidal volume, worsening air tapping, and REM atonia, hypoventilation can be exacerbated during the sleeping hours. We present four patients who were prescribed nocturnal Volume Assured Pressure Support VAPS for their progressive hypercapnia. Report of case(s) Subject 1 is a 72 year old female with severe bronchiectasis and restrictive lung disease due to TB pneumonia at a young age. Subject 2 is a 45 year old male with history of pulmonary cavitation due to extensive TB disease when he was younger. Subject 3 is a 45-year-old woman with rheumatoid arthritis related ILD with associated pulmonary arterial hypertension. Subject 4 is a 74 year old patient with a bilateral lung transplant for IPF complicated by bronchiolitis obliterans syndrome who presented with progressive dyspnea and hypercapnia. Despite optimal therapy, all of these patients were admitted for hypercapnic and hypoxemic respiratory failure requiring treatment with BPAP then transitioned to nocturnal VAPS on discharge. For all patients, dyspnea and pCO2 improved as outpatients although all patients did eventually experience an exacerbation of their lung disease requiring repeat admission. Conclusion Due to the physiologic changes that occur with sleep, patients with severe lung disease may experience worsening CO2 retention while sleeping. There is little data assessing the use of chronic nocturnal non-invasive ventilation (NIV) to treat the hypercapnia of chronic lung diseases other than chronic obstructive pulmonary disease, extra-thoracic restriction, and neuromuscular disease. In this case series, nocturnal VAPS stabilized and/or reduced pCO2 in patients with pulmonary parenchymal disease of various etiologies. Additional studies are needed to assess long term effects of VAPS in these patients, including exacerbations, symptoms, and overall mortality. Support (if any):

Abstract Introduction Many patients with interstitial lung disease (ILD) experience progressive respiratory failure. While various therapies are implemented for acute hypercapnic respiratory failure during inpatient ILD flares, there is little data regarding the management of chronic hypercapnia in ILD with nocturnal Volume Assured Pressure Support (VAPS). We present three patients who were prescribed nocturnal VAPS for their progressive hypercapnia as a bridge to lung transplantation. Report of Case Patient 1 is a 45-year-old woman with rheumatoid arthritis related ILD and progressive hypercapnia. Despite optimal therapy, her ILD resulted in an admission for hypercapnic and hypoxemic respiratory failure requiring treatment with BPAP, then transition to nocturnal VAPS on discharge. Dyspnea and pCO2 improved as an outpatient (Fig. 1). Patient 2 is a 70-year-old female with history of scleroderma associated ILD with severe PH and hypercapnia. Initiation of VAPS improved her pCO2 levels although she was readmitted after a few months of treatment for an ILD flare. Patient 3 is a 60-year-old patient with connective tissue disease related ILD who was admitted for respiratory failure due to pneumonia and was transitioned to BPAP for hypercapnic respiratory failure. Due to insurance issues she has been unable to obtain a home VAPS and her pCO2 remains elevated. A plot of each patient’s pCO2 over time is in Figure 1. Conclusion In patients with severe lung disease, the normal decrease in tidal volumes that occurs with sleep can result in CO2 retention. Non-invasive ventilation (NIV) is well-studied in both stable obstructive lung disease and exacerbations but there is little data examining the utility of NIV to treat the chronic hypercapnia of ILD. In this case series, nocturnal VAPS stabilized or reduced PCO2 in patients with ILD and hypercapnia. Additional studies are needed to assess long term effects of VAPS in these patients.

Patients requiring mechanical ventilation (MV) beyond 21 days, usually referred to as prolonged MV, represent a unique group with significant medical needs and a generally poor prognosis. Research suggests that approximately 10% of all MV patients will need prolonged ventilatory care, and that number will continue to rise. Although we have extensive knowledge of MV in the acute care setting, less is known about care in the post-ICU setting. More than 50% of patients who were deemed unweanable in the ICU will be liberated from MV in the post-acute setting. Prolonged MV also presents a challenge in care for medically complex, elderly, socioeconomically disadvantaged and marginalized individuals, usually at the end of their life. Patients and their families often rely on ventilator weaning facilities and skilled nursing homes for the continuation of care, but home ventilation is becoming more common. The focus of this review is to discuss recent advances in the weaning strategies in prolonged MV, present their outcomes and provide insight into the complexity of care.

Background: Survivors of COVID-19 pneumonia often suffer from chronic critical illness (CCI) and require long-term hospitalization. Long-term acute care (LTAC) hospitals are vital in the care of CCI patients, but their role for patients post COVID-19 infection is not known. Barlow Respiratory Hospital (BRH) is a 105-bed, LTAC hospital network serving ventilator-dependent and medically-complex patients transferred from the ICUs of hospitals in southern California. We report patient characteristics of our first series of COVID-19 survivors admitted to the post-acute venue of an LTAC hospital. Methods: Single-center observational descriptive report of patients recovering from acute infectious complications of COVID-19 pneumonia requiring long-term respiratory support. Results: From 28 April to 7 September 2020, 41 patients were admitted to BRH for continued recovery from COVID-19 pneumonia. The length of stay at the transferring hospital was twice that of non-COVID patients admitted during the same time period. Median age: 68 [44-94] years, 61% male, 80.5% with tracheostomy, 51.2% on invasive mechanical ventilation, 22% receiving hemodialysis. All mechanical ventilation and hemodialysis interventions were initiated at the transferring hospital. Conclusions: To our knowledge, this is the first report to characterize CCI and medically complex COVID-19 patients transferred to the post-acute venue of an LTAC hospital. Patients on average spent over six weeks in the transferring hospital mostly in the ICU, are largely elderly, carry the known risk factors for COVID-19 infection, and experienced respiratory failure necessitating prolonged mechanical ventilation via tracheostomy. Our findings suggest that these patients will continue to require considerable medical interventions and treatments, including weaning from mechanical ventilation, owing to the numerous sequelae of the infection and the burden of acute-on-chronic diseases. As ICU survival rates improve, this research further emphasizes the important role of the LTAC hospital in responding to the COVID-19 crisis.