Pre-Existing Psychiatric Illness Is Associated With an Increased Risk of Delirium in Patients With Acute Respiratory Distress Syndrome.

BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) are highly susceptible to developing delirium for a multitude of reasons. Previous studies have linked pre-existing depression with an increased risk of postoperative delirium in patients undergoing cardiac and non-cardiac surgery. However, the evidence regarding the association between pre-existing psychiatric illnesses and delirium in ARDS patients is unknown. In this study, we aim to determine the relationship between pre-existing psychiatric illness and the risk of development of delirium amongst ARDS patients. STUDY DESIGN AND METHODS: We performed a retrospective study of a mixed group of patients admitted to the intensive care unit (ICU) between January 2016 and December 2019 with a diagnosis of ARDS per the Berlin definition. The study group was divided into 2 cohorts: subjects with delirium and subjects without delirium. Comparison between the 2 groups was conducted to examine the impact of pre-existing psychiatric illnesses including major depressive disorder (MDD), generalized anxiety disorder (GAD), bipolar disorder, schizophrenia, or post-traumatic stress disorder. Multivariable logistic regression analysis was performed adjusting for benzodiazepine use, sedatives, analgesics, sequential organ failure assessment score, and corticosteroid use to determine the association between pre-existing psychiatric disorders and delirium. RESULTS: 286 patients with ARDS were identified; 124 (43%) of whom were diagnosed with ICU delirium. In patients diagnosed with ICU delirium, 49.2% were found to have preexisting psychiatric illnesses, compared to 34.0% without any preexisting psychiatric illness (OR = 1.94, P = 0.01). In a subgroup analysis of individual psychiatric illnesses, GAD and MDD were associated with the development of delirium (OR = 1.88, P = 0.04 and OR = 1.76, P = 0.05 respectively). INTERPRETATION: ARDS patients with preexisting psychiatric illnesses, particularly GAD and MDD are associated with an increased risk of developing ICU delirium. Clinicians should be aware of the effect of psychiatric co-morbidities on developing delirium in critically ill patients.

Prevalence and Characteristics of Hyperthyroidism Among Patients With Sarcoidosis in the United States.

OBJECTIVE: We aimed to determine the prevalence and clinical characteristics of self-reported hyperthyroidism in patients with sarcoidosis. METHODS: A national registry-based study investigating 3836 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire in the period between June 2014 and August 2019 was conducted. This registry is generated from a web-based questionnaire that is self-reported by patients with sarcoidosis. We compared patients with sarcoidosis who had hyperthyroidism with those who did not. We used multivariate logistic regression analysis to study the association between hyperthyroidism and different cardiac manifestations in patients with sarcoidosis. RESULTS: Three percent of the study respondents self-reported having hyperthyroidism and were generally middle-aged Caucasian women. Compared with patients without hyperthyroidism, patients with hyperthyroidism had more sarcoidosis-related comorbidities (59% vs 43%, P = .001) and more steroid-related comorbidities (56% vs 44%, P = .01), but there was no difference in the sarcoidosis-specific treatments they received, which included corticosteroids. Patients with hyperthyroidism reported sarcoidosis involvement of the heart (26.6% vs 14.9%, P = .005), kidneys (14.9% vs 8%, P = .033) and sinuses (17.7% vs 10.2%, P = .030) more frequently. Cardiac manifestations that were more frequently reported in patients with hyperthyroidism included atrial arrhythmias (11.3% vs 6.3%, P = .046), ventricular arrhythmias (17.2% vs 7.5%, P < .001), congestive heart failure (10.4% vs 5%, P = .017), and heart block (9.4% vs 4.7%, P = .036). CONCLUSION: Hyperthyroidism is infrequent in patients with sarcoidosis but is potentially associated with different cardiac manifestations. We suggest considering routine screening for hyperthyroidism in patients with sarcoidosis, especially in those with cardiac involvement. Further studies are needed to investigate the impact of identifying and treating hyperthyroidism in patients with sarcoidosis.

Hypersensitivity Pneumonitis With and Without Autoimmune Features: A Clinical Comparative Analysis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by an immunological reaction to repeated inhalational exposure to antigens. The etiology and exact immunopathology are poorly understood. Autoimmunity overlapping with HP has been described but the role of concomitant autoimmunity in the clinical course and outcome of the HP is not clearly established. In this study, we examined patients diagnosed with HP and compare them to patients with concomitant HP and autoimmunity. METHODS: Patients were retrospectively screened from a single-center ILD registry. Patients > 18 years with an established multidisciplinary diagnosis of HP were included in the study. Patients with HP without autoimmune features and patients with HP with autoimmune features (HPAF) were assessed. We compared the demographics, clinical characteristics, treatment, and outcomes between the two groups. We used a Cox proportional hazards model to compare lung transplant-free survival outcomes of patients with HPAF to those with non-HPAF HP patients. RESULTS: Of 73 patients with HP, 43 were diagnosed with HPAF. Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to non-HPAF HP patients [48.8 vs 23.3%, p = 0.028, Crude odds ratio (cOR) = 3.14]. Symptomatically, those with HPAF reported a higher prevalence of arthritis as compared to non-HPAF HP (20.9 vs 3.3%, p = 0.040, cOR = 7.68). No significant differences between pulmonary function tests, oxygen requirements, mortality, and lung transplantation rates were found between the two groups. There was no statistically significant difference in transplant-free survival (p = 0.836). CONCLUSION: Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to patients with non-HPAF HP. The clinical characteristics and outcomes did not differ between the two groups and concomitant autoimmunity among the HP group did not portend a poorer prognosis.

Ustekinumab associated chronic eosinophilic pneumonia.

INTRODUCTION: Ustekinumab-induced eosinophilic pneumonia is rare and to our knowledge, this is the fifth reported case of such an entity. CASE STUDY: A 60-year-old female was admitted with worsening shortness of breath and a nonproductive cough for 4 months. Her past medical history was significant for Crohn's disease and psoriatic arthritis that was previously managed with adalimumab and switched to ustekinumab 2 months before symptoms. Initial diagnostic workup showed 10% peripheral eosinophilia and a CT chest showed numerous 5 mm nodules scattered throughout the lungs along with some peripheral reticulations. Her BAL fluid analysis showed abnormally high eosinophil count (67%), greatly limiting her potential diagnoses to eosinophilic pneumonia, EGPA, and tropical pulmonary eosinophilia (TPE). AEP typically causes more severe disease with a rapid onset, and there was low suspicion for TPE based on history, leaving EGPA and CEP. Based on her negative autoimmune serology, a negative biopsy of the nasal mucosa (no vasculitis/granulomata or eosinophils), and negative infectious workup, the patient was diagnosed with CEP secondary to ustekinumab and the drug was stopped. She was started on high dose prednisone and after a prolonged taper over 5 months, her symptoms and nodules and reticulations on her CT scan resolved. DISCUSSION: This case exemplifies the importance of identifying drug-induced lung diseases which in many cases might not have a strong temporal association with the symptom onset. It also highlights that some drugs owing to their long elimination half-time can remain in the system for a prolonged period and continues to cause symptoms despite their cessation and require prolonged treatment and reassurance. CONCLUSION: The association of eosinophilic pneumonia with ustekinumab, a drug used in the treatment of psoriasis and other autoimmune diseases, is rare and there is a paucity of literature regarding this association.

A rare case of refractory asthma managed with azathioprine.

Introduction: Azathioprine is an immune-modulating agent used in the management of autoimmune diseases and in preventing graft rejection. Its role in the management of refractory asthma is not very well-established.Case study: A 47-year-old female with an underlying severe refractory asthma, managed with high dose steroids, was seen as an outpatient. Her course was complicated by frequent asthma exacerbation and severe adverse effects of chronic steroid use. Her symptoms did not respond to standard asthma management per Guidelines for the Diagnosis and Management of Asthma 1. She was tried on other management which included methotrexate and omalizumab injections without success. Azathioprine was started as a steroid-sparing agent following which her symptoms showed dramatic improvement with fewer exacerbations, higher peak flow measurements, and she was able to wean down her daily prednisone dose from 60 mg/day to 5 mg/day.Conclusion: Azathioprine is still an investigational agent for the management of asthma and more research needs to be done to evaluate its role. To our knowledge, this is the second case report which details the therapeutic role of Azathioprine in the management of asthma.

Features of patients with gastrointestinal bleeding after implantation of ventricular assist devices.

BACKGROUND & AIMS: Ventricular assist devices (VADs) are used to treat patients with end-stage heart disease. However, patients with VADs frequently develop gastrointestinal (GI) bleeding. We investigated the incidence, etiology, and outcome of GI bleeding in patients with VADs. METHODS: In a retrospective study, we analyzed data from 391 consecutive patients (mean age, 53.9 ± 14.2 years; 81% male) who underwent VAD implantation for end-stage heart disease from January 2000 through May 2012 at the Cleveland Clinic. Multivariable logistic regression analysis was used to identify factors independently associated with GI bleeding in patients with VADs. RESULTS: Sixty-two patients (15.9%) had GI bleeding. The risk of GI bleeding increased by 10% for every 5-year increase in age (P = .006). GI bleeding was also associated with lower body mass index (P = .046), current smoking (P = .007), and lower baseline levels of hemoglobin (P < .001). Bleeding was primarily overt (79%), and most patients presented with hematochezia (43.5%). Causes of bleeding were primarily vascular malformations (26.5%) and ulcers (26.5%). Patients who received VADs as their only therapy, rather than as a bridge-to-transplantation, were more likely to have GI bleeding (P = .008). Colonoscopy detected GI bleeding with the highest diagnostic yield; most bleeding was associated with colonic lesions (51.4%). Overall mortality was 39.4%, and 2 deaths were directly related to GI bleeding. CONCLUSIONS: On the basis of a large case series analysis, GI bleeding is common after implantation of VADs (15.9% of patients have at least 1 episode of bleeding). Episodes were mostly overt and predominantly from the lower GI tract; colonoscopy is the best method of detection.

Can a validated sleep apnea scoring system predict cardiopulmonary events using propofol sedation for routine EGD or colonoscopy? A prospective cohort study.

BACKGROUND: Obstructive sleep apnea (OSA), which is linked to the prevalence of obesity, continues to rise in the United States. There are limited data on the risk for sedation-related adverse events (SRAE) in patients with undiagnosed OSA receiving propofol for routine EGD and colonoscopy. OBJECTIVE: To identify the prevalence of OSA by using the STOP-BANG questionnaire (SB) and subsequent risk factors for airway interventions (AI) and SRAE in patients undergoing elective EGD and colonoscopy. DESIGN: Prospective cohort study. SETTING: Tertiary-care teaching hospital. PATIENTS: A total of 243 patients undergoing routine EGD or colonoscopy at Cleveland Clinic. INTERVENTION: Chin lift, mask ventilation, placement of nasopharyngeal airway, bag mask ventilation, unplanned endotracheal intubation, hypoxia, hypotension, or early procedure termination. MAIN OUTCOME MEASUREMENTS: Rates of AI and SRAE. RESULTS: Mean age of the cohort was 50 ± 16.2 years, and 41% were male. The prevalence of SB+ was 48.1%. The rates of hypoxia (11.2% vs 16.9%; P = .20) and hypotension (10.4% vs 5.9%; P = .21) were similar between SB- and SB+ patients. An SB score ≥3 was found not to be associated with occurrence of AI (relative risk [RR] 1.07, 95% confidence interval [CI] 0.79-1.5) or SRAE (RR 0.81, 95% CI, 0.53-1.2) after we adjusted for total and loading dose of propofol, body mass index (BMI), smoking, and age. Higher BMI was associated with an increased risk for AI (RR 1.02; 95% CI, 1.01-1.04) and SRAE (RR 1.03; 95% CI, 1.01-1.05). Increased patient age (RR 1.09; 95% CI, 1.02-1.2), higher loading propofol doses (RR 1.4; 95% CI, 1.1-1.8), and smoking (RR 1.9; 95% CI, 1.3-2.9) were associated with higher rates of SRAE. LIMITATIONS: Non-randomized study. CONCLUSION: A significant number of patients undergoing routine EGD and colonoscopy are at risk for OSA. SB+ patients are not at higher risk for AI or SRAE. However, other risk factors for AI and SRAE have been identified and must be taken into account to optimize patient safety.

Effect of Obesity on Mortality in Pulmonary Hypertension-A Systematic Review and Meta-Analysis.

Obesity is reported to have a protective effect on mortality in pulmonary hypertension (PH), a phenomenon known as obesity paradox. However, the data are conflicting, with some studies showing decreased mortality while other studies found no effect of obesity on mortality. Therefore, we performed a systematic review and meta-analysis to examine whether there is an association between obesity and mortality in PH. Only patients with PH diagnosed by right heart catheterization were included. We also performed a sub-group analysis of subjects with pre-capillary PH only. A total of six studies met the inclusion criteria, with a sample size of 13,987 patients. Obese subjects had lower mortality compared to non-obese subjects in the combined pre- and post-capillary PH group (hazard ratio 0.79, 95% CI 0.66-0.95, p = 0.01). While obesity was associated with reduction in mortality in the pre-capillary PH group (hazard ratio 0.77, 95% CI 0.60 to 0.98, p = 0.03), this was not uniform across all studies.

Precapillary pulmonary arterial hypertension in a patient with Proteus syndrome.

Proteus syndrome is a rare progressive multisystem disorder characterized by asymmetric, disproportionate overgrowth of bone, skin, and other tissue types. Molecular pathogenesis has been identified as somatic activating mutations of the AKT1 gene. The presentation of Proteus syndrome is exceptionally variable. Respiratory complications include emphysematous lung disease and predisposition to pulmonary emboli, the latter of which is a significant source of mortality. Pulmonary hypertension due to longstanding hypoxic lung disease as well as chronic thromboembolic events has been observed in this population. In contrast, precapillary pulmonary arterial hypertension in the absence of chronic pulmonary emboli and parenchymal lung disease has not been described in the literature on patients with Proteus syndrome. We report such a case in a young patient with Proteus syndrome, reviewing subsequent management and emphasizing the need for a detailed investigation of dyspnea.

Echocardiographic characteristics of patients with antisynthetase syndrome.

Right ventricular (RV) dysfunction and pulmonary hypertension (PH) occurs in approximately one-third of patients with interstitial lung disease (ILD) and is associated with reduced 6-minute walk distance (6MWD), and increased hospitalizations and mortality. Although the impact of RV dysfunction and PH has been well described in several types of ILD, data is scarce on antisynthetase syndrome. Therefore, we sought to examine the presence of RV dysfunction and PH in patients with antisynthetase syndrome and the impact on clinical outcomes. We conducted a retrospective study of patients with antisynthetase syndrome. Seventy-five subjects were identified. Fifty-one (68%) subjects had echocardiographic data. Patients were grouped into those with normal fractional area change (FAC) ≥ 35% and reduced FAC < 35%. Clinical, echocardiographic, and right heart catheterization data were compared between the two groups. Subjects with FAC < 35% had lower diffusion capacity of the lung for carbon monoxide (29% vs. 47%, p = 0.004), fibrotic features on computed tomography of the chest (79% vs. 33%, p = 0.005), larger RV diameter (5.4 vs. 3.9 cm, p < 0.001), higher right atrial pressures (8 vs. 5 mmHg, p = 0.02), and required supplemental oxygen more frequently (100% vs. 44%, p < 0.001) compared to those with FAC ≥ 35%. We found no difference in 6MWD and hospitalizations between the two groups. The presence of RV dysfunction in antisynthetase syndrome may identify patients at risk of poor outcomes.

Sarcoidosis-associated acro-osteolysis.

Sarcoidosis is characterised by the formation of noncaseating granulomas classically affecting lungs, lymph nodes and skin. Osteoarticular involvement affects up to 15% of patients; however, acro-osteolysis, destruction involving distal phalanges of fingers and toes, associated with sarcoidosis, is extremely rare. A 44-year-old woman with a history of biopsy-proven sarcoidosis managed with prednisone and methotrexate presented with swelling and pain in the distal fingers of her right hand without skin manifestations. Radiographic imaging showed erosion of distal phalanges on second, third and fifth fingers and bone resorption in bilateral toes. A biopsy of the finger lesions showed noncaseating granulomas consistent with sarcoidosis. She was diagnosed with sarcoid acro-osteolysis and started on adalimumab with clinical and radiographic improvement. While most cases of osteoarticular sarcoidosis are asymptomatic and respond to standard immunosuppression, we present a case with progressive and refractory clinical course. This is the first reported case of sarcoid acro-osteolysis affecting the toes.

COVID-19 infection and severe rhabdomyolysis.

Although patients with COVID-19 can have mild nonspecific myalgia and mild elevation of creatinine kinase levels, severe myalgia along with elevation of creatinine kinase levels >10 times the upper normal limit and dark-colored urine indicate an underlying severe rhabdomyolysis. This report describes a 60-year-old morbidly obese man who was found to have severe rhabdomyolysis, along with acute kidney injury, dark-colored urine, and a positive COVID-19 test. He had a prolonged hospital course requiring continuous renal replacement therapy, mechanical ventilation, and multiple vasopressors and eventually died of multiorgan failure. The management of severe rhabdomyolysis and COVID-19 is challenging, and fluid resuscitation should be done cautiously, monitoring for early signs of fluid overload.

Macrophage activating syndrome causing decompensated right heart failure.

BACKGROUND: Macrophage activating syndrome (MAS) is a form of hemophagocytic lymphohistiocytosis (HLH), a rare complication of autoimmune disease that is characterized by cytokine storm and multiorgan failure. CASE SUMMARY: A 32-year-old male presented with acutely decompensated pulmonary arterial hypertension and right heart failure secondary to MAS. The patient was immediately started on inhaled and intravenous epoprostenol, vasopressors and dexamethasone and anakinra were administered. Despite the therapies given, the patient's condition continued to decline, and he was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. Over a few days, his clinical condition improved, and he was decannulated from VA-ECMO and later transitioned oral treprositinil and was discharged home. Due to its non-specific clinical manifestations, the diagnosis of MAS depends on high clinical suspicion and initial laboratory work up such as thrombocytopenia, transaminitis, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, etc. In our patient, MAS led to decompensated Pulmonary Arterial Hypertension (PAH) leading to right heart failure that was refractory to inhaled and intravenous epoprostenol and vasopressors and required VA-ECMO as a bridge to recovery while his MAS was managed by anakinra and dexamethasone. CONCLUSION: MAS can result in acute decompensation of PAH and right heart failure. Besides RV failure management, immunosuppressants such as anakinra, etoposide, etc. should be utilized early in the management of MAS. In refractory right heart failure, VA-ECMO can be considered as a bridge to recovery. There is a paucity of literature supporting the utilization of VA-ECMO in the management of refractory right heart failure caused by MAS in adults and much of the data stems from pediatric studies. This case serves as a fine example of successful use of VA-ECMO in adult population.

Sarcoidosis among US Hispanics in a Nationwide Registry.

BACKGROUND: Sarcoidosis has been well studied in multiple races and ethnic groups. However, there is a paucity of data that describes sarcoidosis in Hispanics. We aimed to determine the prevalence of Hispanic ethnicity, clinical characteristics and impact of sarcoidosis among Hispanics from a US based national registry. METHODS: We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire. This registry is a web-based, self-reported questionnaire that provides data related to demographics, diagnostics, organ involvement, treatment modalities, and the physical and psychosocial impact of sarcoidosis. We compared Hispanic patients to non-Hispanics. We performed multivariate logistic regression analysis adjusting for age, gender, education, income and insurance status and looked at the association between Hispanic ethnicity with depression, chronic pain syndrome, chronic fatigue syndrome, impact on family finances, employment-based disability and job termination. RESULTS: Nine percent of the patients reported a Hispanic ethnicity and the majority of these patients self-identified as white women. The most common organs involved were the lungs (74.9%), central lymph nodes (53.8%), and peripheral lymph nodes (37.1%). Hispanics reported more peripheral nerves and peripheral lymph nodes involvement than non-Hispanics. Hispanics experienced more depression, sleep apnea, and chronic pain syndrome than non-Hispanics. The use of mobility assistive devices was more common among Hispanics, as well as employment-based disability, and disease-related job termination compared to non-Hispanics. The majority of Hispanics reported significantly more pain that interfered with the enjoyment of life than non-Hispanics. On multivariate logistic regression analysis, Hispanic ethnicity was associated with depression (adjusted odds ratio (aOR) = 1.5; 95% CI: 1.01-2.2), chronic pain syndrome (aOR = 1.7; 1.1-2.6), job termination due to sarcoidosis (aOR = 1.7; 1.1-2.7) and higher impact on family finances (aOR = 1.7; 1.1-2.5). CONCLUSION: The clinical presentation of sarcoidosis in Hispanic patients differs from that in non-Hispanic patients living in the United States. These differences should be considered when managing Hispanic patients with sarcoidosis. We encourage more studies that investigate phenotyping among Hispanics with sarcoidosis.

First case of minimal change nephrotic syndrome resolving with antifungal therapy for isolated pleural cryptococcal infection.

We report the case of a 71-year-old male with poorly controlled diabetes mellitus who presented with lower extremity edema and acute renal failure. He was diagnosed with nephrotic syndrome secondary to minimal change disease (MCD). Treatment with steroids was withheld due to concern for hyperglycemia in the context of his poorly controlled diabetes mellitus. A week after discharge, he was subsequently re-hospitalized four times within a month with pleural effusions, dyspnea, and fever. Work up revealed isolated pleural cryptococcosis, demonstrated on two separate admissions. There was neither evidence of disseminated disease nor immunocompromising condition. Immunosuppression was not initiated for the treatment of MCD in the setting of poorly controlled diabetes and active infection. After six months of treatment with fluconazole 400 mg/day, the nephrotic syndrome, renal failure, and cryptococcal pleuritis resolved. This case is the first to our knowledge of isolated pleural cryptococcosis associated with nephrotic syndrome. The patient's course lends further support to the hypothesis that there may be causal relationship between cryptococcosis and nephrotic syndrome.

Higher Class of Obesity Is Associated With Delivery of Higher Tidal Volumes in Subjects With ARDS.

BACKGROUND: Obese subjects are at higher risk of development and progression of ARDS. There are limited data regarding mechanical ventilation practices and use of adjunctive therapies in subjects with ARDS across different obesity classes. We hypothesized that the adherence to lung-protective ventilation would be worse with rising body mass index class in patients with ARDS. METHODS: We conducted a retrospective observational study of subjects with ARDS. We evaluated the differences in ventilator settings, airway pressures, gas exchange, use of rescue therapies, length of hospital stay, and mortality among subjects based on the obesity classes of the WHO. RESULTS: The study included 613 subjects with ARDS: 21.4% were normal weight, 25% were overweight, and 53.7% were obese; 33.3% of the obese subjects met criteria for class I-II obesity, while 20.4% were class III obese (morbid obesity). On day 1, 53% of subjects with class III obesity had tidal volumes > 8 mL/kg, compared to 26% of the subjects with normal weight. In addition, 48% of the morbidly obese subjects received at least one rescue therapy as compared to 37% of normal weight subjects and 36% of overweight subjects. There were significant differences in the use of rescue therapies among the groups. In a multivariable model, subjects with class III obesity were significantly more likely to receive tidal volume > 8 mL/kg predicted body weight on day 1 when compared with subjects with normal weight (odds ratio 3.14, 95% CI 1.78-5.57). There was no difference in length of stay in ICU or hospital, duration of mechanical ventilation, or adjusted ICU or hospital mortality among the 4 groups. CONCLUSIONS: In this study, the risk of exposure to higher tidal volumes and the need for specific rescue therapies rose with higher classes of obesity in subjects with ARDS. More research is needed to identify how to better implement lung-protective ventilation in patients with obesity.