A rare pulmonary manifestation of Crohn's disease: Acute fibrinous and organizing pneumonia presenting as multifocal nodules.

Acute Fibrinous and Organizing Pneumonia (AFOP) is a rare pulmonary disease, and it has not been recorded in literature as a pulmonary manifestation of Crohn's disease. A 22-year-old individual with an extensive history of Crohn's disease presented to the hospital initially for hematochezia and diarrhea. Computed tomography of her abdomen and pelvis showed multiple pulmonary nodules bilaterally. The patient did not report cough, sputum production, or dyspnea. Autoimmune and infectious workup were overall unremarkable. A CT-guided percutaneous biopsy of a peripheral lung nodule was performed showing features consistent with AFOP. The patient was ultimately treated with a long taper of prednisone and Ustekinumab for Crohn's disease. Follow-up CT-chest showed interval reduction and improvement in lung nodules, which correlated with better control of the patient's Crohn's disease. Pulmonary manifestations of IBD are varied, including pleural disease, bronchiectasis, and organizing pneumonia. Bronchiolitis obliterans organizing pneumonia has been described more frequently in patients with ulcerative colitis compared to Crohn's. Pulmonary nodules are a rare manifestation of IBD and often tend to be granulomatous or necrobiotic. AFOP is a rare entity with no previously reported association with IBD. Secondary AFOP can be caused by autoimmune diseases, drug reactions, infections, or radiation. Treatment of AFOP is usually immunosuppression by glucocorticoids.

Autopsy study of fatal invasive pulmonary aspergillosis: Often undiagnosed premortem.

Invasive aspergillosis (IA) is a serious complication in immunocompromised and critically ill patients but is difficult to diagnose. We sought to examine how often cases go undiagnosed and to understand the presenting clinical and radiologic features associated with fatal IA. We reviewed cases of fatal IA confirmed at autopsy (N = 67) between 1999 and 2019 at a tertiary academic hospital. At autopsy, pulmonary involvement was present in 97% of cases--46% were limited to the lungs and 51% had concomitant extrapulmonary involvement. Immunosuppression with either glucocorticoids and/or other immunosuppressive agents was present in 85%. Among those not immunocompromised (15%), chronic lung disease was present in 70%, and a respiratory coinfection was found in 50%. Chest imaging abnormalities including consolidation, ground glass opacities, halo sign, cavitation, and air crescent sign were present in 49%, 49%, 37%, 22%, and 7% of cases, respectively. Diagnostic bronchoscopy was performed in 61% of cases and yielded aspergillus in 63% of those cases by either bronchoalveolar lavage (galactomannan and/or culture), bronchial washings, or transbronchial biopsy cultures. Either a respiratory coinfection or other systemic coinfection was diagnosed in 64%. The performance of diagnostic bronchoscopy was associated with accurate pre-mortem identification of IA (p = 0.001). Clinicians correctly identified IA as the cause of death in only 27% of fatal IA cases identified at autopsy. Complex presenting features, high rates of co-infections, and low rates of invasive diagnostic procedures may have led to missed diagnoses of IA.

Inpatient Management of Pulmonary Embolism: Clinical Characteristics and Mortality in a High-Volume Tertiary Care Center.

The optimal management strategy for submassive or intermediate risk pulmonary embolism (IRPE)-anticoagulation alone versus anticoagulation plus advanced therapies-remains in equipoise leading many institutions to create multidisciplinary PE response teams (PERTs) to guide therapy. Cause-specific mortality of IRPE has not been thoroughly examined, which is a meaningful outcome when examining the effect of specific interventions for PE. In this retrospective study, we reviewed all adult inpatient admissions between 8/1/2018 and 8/1/2019 with an encounter diagnosis of PE to study all cause and PE cause specific mortality as the primary outcomes and bleeding complications from therapies as a secondary outcome. There were 429 total inpatient admissions, of which 59.7% were IRPE. The IRPE 30-day all-cause mortality was 8.7% and PE cause-specific mortality was 0.79%. Treatment consisted of anticoagulation alone in 93.4% of cases. Advanced therapies-systemic thrombolysis, catheter directed thrombolysis, or mechanical thrombectomy, were performed in only six IRPE cases (2.3%). Decompensation of IRPE cases requiring higher level of care and/or rescue advanced therapy occurred in only five cases (2%). In-hospital major bleeding and clinically relevant non-major bleeding were more common in those receiving systemic thrombolysis (61.5%) compared to anticoagulation combined with other advanced therapies (11.7%). Despite the high overall acuity of PE cases at our institution, in-hospital all-cause mortality was low and cause-specific mortality for IRPE was rare. These data suggest the need to target other clinically meaningful outcomes when examining advanced therapies for IRPE.

Myocardial Infarction and Cardiac Arrest in a Patient With Severe Undiagnosed Hypothyroidism During Bronchoscopy.

Thyroid hormones have an integral role in cardiac homeostasis, and hypothyroidism may be associated with impaired myocardial contractility, altered endothelial function, and blunted response to catecholamines. Herein, the case of a patient with undiagnosed severe hypothyroidism, who developed an acute myocardial infarction and cardiac arrest during sedation for bronchoscopy, is described. He required prolonged resuscitation, which included coronary catheterization and placement of an intra-aortic balloon pump. The resuscitation was noteworthy for blunted physiologic responses to large doses of epinephrine; in particular, persistent bradycardia without evidence of conduction abnormalities. On admission to the intensive care unit, he was hypothermic (31.4°C), bradycardic, and hypotensive. Laboratory investigations revealed profound hypothyroidism, and thyroid hormone replacement was initiated. Within hours of initiation of thyroid hormone replacement, the need for vasopressor support was reduced. He had a complete recovery and was discharged home neurologically intact. The authors of the present report believe that this favorable neurologic outcome could be attributed to efficient resuscitation, prompt coronary revascularization, and profound hypothermia likely related to a hypothyroidism-associated hypometabolic state.

A comparison of 2 visual methods for classifying obstructive vs central hypopneas.

STUDY OBJECTIVES: Rules for classifying apneas as obstructive, central, or mixed are well established. Although hypopneas are given equal weight when calculating the apnea-hypopnea index, classification is not standardized. Visual methods for classifying hypopneas have been proposed by the American Academy of Sleep Medicine and by Randerath et al (Sleep. 2013;36[3]:363-368) but never compared. We evaluated the clinical suitability of the 2 visual methods for classifying hypopneas as central or obstructive. METHODS: Fifty hypopnea-containing polysomnographic segments were selected from patients with clear obstructive or clear central physiology to serve as standard obstructive or central hypopneas. These 100 hypopnea-containing polysomnographic segments were deidentified, randomized, and scored by 2 groups. We assigned 1 group to use the American Academy of Sleep Medicine criteria and the other the Randerath algorithm. After a washout period, re-randomized hypopnea-containing polysomnographic segments were scored using the alternative method. We determined the accuracy (agreement with standard), interrater (Fleiss's κ), and intrarater agreement (Cohen's κ) for obtained scores. RESULTS: Accuracy of the 2 methods was similar: 67% vs 69.3% for Randerath et al and the American Academy of Sleep Medicine, respectively. Cohen's κ was 0.01-0.75, showing that some raters scored similarly using the 2 methods, while others scored them markedly differently. Fleiss's κ for the American Academy of Sleep Medicine algorithm was 0.32 (95% confidence interval, 0.29-0.36) and for the Randerath algorithm was 0.27 (95% confidence interval, 0.23-0.30). CONCLUSIONS: More work is needed to discover a noninvasive way to accurately characterize hypopneas. Studies like ours may lay the foundation for discovering the full spectrum of physiologic consequences of obstructive sleep apnea and central sleep apnea.

Single-molecule imaging of NGF axonal transport in microfluidic devices.

Nerve growth factor (NGF) signaling begins at the nerve terminal, where it binds and activates membrane receptors and subsequently carries the cell-survival signal to the cell body through the axon. A recent study revealed that the majority of endosomes contain a single NGF molecule, which makes single-molecule imaging an essential tool for NGF studies. Despite being an increasingly popular technique, single-molecule imaging in live cells is often limited by background fluorescence. Here, we employed a microfluidic culture platform to achieve background reduction for single-molecule imaging in live neurons. Microfluidic devices guide the growth of neurons and allow separately controlled microenvironment for cell bodies or axon termini. Designs of microfluidic devices were optimized and a three-compartment device successfully achieved direct observation of axonal transport of single NGF when quantum dot labeled NGF (Qdot-NGF) was applied only to the distal-axon compartment while imaging was carried out exclusively in the cell-body compartment. Qdot-NGF was shown to move exclusively toward the cell body with a characteristic stop-and-go pattern of movements. Measurements at various temperatures show that the rate of NGF retrograde transport decreased exponentially over the range of 36-14 degrees C. A 10 degrees C decrease in temperature resulted in a threefold decrease in the rate of NGF retrograde transport. Our successful measurements of NGF transport suggest that the microfluidic device can serve as a unique platform for single-molecule imaging of molecular processes in neurons.

Optically resolving individual microtubules in live axons.

Microtubules are essential cytoskeletal tracks for cargo transportation in axons and also serve as the primary structural scaffold of neurons. Structural assembly, stability, and dynamics of axonal microtubules are of great interest for understanding neuronal functions and pathologies. However, microtubules are so densely packed in axons that their separations are well below the diffraction limit of light, which precludes using optical microscopy for live-cell studies. Here, we present a single-molecule imaging method capable of resolving individual microtubules in live axons. In our method, unlabeled microtubules are revealed by following individual axonal cargos that travel along them. We resolved more than six microtubules in a 1 microm diameter axon by real-time tracking of endosomes containing quantum dots. Our live-cell study also provided direct evidence that endosomes switch between microtubules while traveling along axons, which has been proposed to be the primary means for axonal cargos to effectively navigate through the crowded axoplasmic environment.