Oral Positive Expiratory Pressure Device for Excessive Dynamic Airway Collapse Caused by Emphysema.

Excessive dynamic airway collapse (EDAC) contributes to breathlessness and reduced quality of life in individuals with emphysema. We tested a novel, portable, oral positive expiratory pressure (o-PEP) device in a patient with emphysema and EDAC. MRI revealed expiratory tracheal narrowing to 80 mm2 that increased to 170 mm2 with the o-PEP device. After 2-weeks use of the o-PEP device for 33% to 66% of activities, breathlessness, quality of life, and exertional dyspnea improved compared with minimal clinically important differences (MCID): University of California-San Diego Shortness of Breath questionnaire score declined 69 to 42 (MCID, ≥5), St. George's Respiratory Questionnaire score decreased 71 to 27 (MCID, ≥4), and before and after the 6-minute walk test Borg score difference improved from Δ3 to Δ2 (MCID, ≥1). During the 6-minute walk test on room air without the use of the o-PEP device, oxyhemoglobin saturation declined 91% to 83%; whereas, with the o-PEP device, the nadir was 90%. Use of the o-PEP device reduced expiratory central airway collapse and improved dyspnea, quality of life, and exertional desaturation in a patient with EDAC and emphysema.

The reverse halo sign and spontaneous pneumothorax due to pulmonary mucormycosis.

Pulmonary mucormycosis (PM) is a rare opportunistic fungal infection that commonly affects immunocompromised patients. Early diagnosis and initiation of appropriate anti-fungal therapy are crucial, as delay in diagnosis leads to increased mortality. However, the diagnosis is often challenging because of the lack of utility of serum markers and low culture sensitivity. Definitive diagnosis often requires invasive tissue sampling, which may delay treatment. Therefore, chest imaging findings play an important role in the diagnosis of suspected cases. This case highlights the importance of classic reverse halo sign and presence of necrotizing cystic changes resulting in spontaneous pneumothorax in a patient who was later found to have invasive PM.

Resting Borg score as a predictor of safe discharge of chronic obstructive pulmonary disease from the emergency department observation unit.

BACKGROUND: Chronic obstructive pulmonary disease exacerbations (eCOPD) can be life-threatening and costly. Emergency department (ED) observation units (ED-Obs) offer short-term care to safely reduce preventable hospitalizations. Accurately identifying eCOPD patients who can be discharged safely will improve outcomes. OBJECTIVES: The objective were to: I) evaluate utility of conventional clinical variables as predictors of safe discharge and II) assess utility of serial resting Borg score and novel Dyspnea Assessment Score (DAS) for identifying eCOPD patients who can be safely discharged from ED-Obs. METHODS: This study was carried out in a 680-bed tertiary, academic hospital with >700 annual eCOPD ED encounters and a 16-bed ED-Obs. A two-phase study of eCOPD patients admitted to ED-Obs was performed. Objective I was a retrospective study including all eCOPD admits from April 2016 to May 2017. Predictor variables (demographics, COPD severity, comorbid conditions, exacerbation severity, clinical care in ED) and outcome variables (ED-Obs disposition, ED revisits) were obtained through electronic medical records. Safe discharge was defined as home disposition from ED-Obs without 7-day revisit. A stepwise regression was performed for predictors of safe discharge. Objective II was a prospective observation study for change in every 4-hour serial resting Borg score and DAS as identifiers of safe discharge. Comparative and receiver operating characteristic (ROC) analyses were performed. A p-value of <0.05 was considered significant. RESULTS: In Objective I, 171 patients with age, FEV1 %, and body mass index of 59.8 (±9.5) years, 35 (±24)%, and 28.8 (±8) m2 /kg were included. After ED-Obs treatment 78 (45.6%) were hospitalized and 93 (54.4%) were discharged home, of whom 11 (6.4%) had 7-day ED revisit. Safe discharge occurred in 82 (48%). None of the predictor variables correlated with safe discharge. In Objective II, of 38 patients included, 20 (52.6%) had safe discharge. Among others, 16 (42%) were hospitalized and two (5.2%) had 7-day ED revisit. The admission Borg scores and DASs were similar in both groups. The predisposition Borg score was significantly lower in patients with safe discharge (2.75 vs. 5.28, p < 0.001) and had the highest area under curve on ROC (0.77) for safe discharge. DAS was not significantly different between groups. CONCLUSIONS: Routine clinical variables do not identify eCOPD patients who can be safely discharged from ED-Obs. Change in resting Borg score during the course of ED-Obs treatment safely identifies patients for discharge. Prospective, external validation is needed to incorporate serial Borg scores in ED-Obs disposition decision for improved safety.

A Case of False-Positive Mycobacterium tuberculosis Caused by Mycobacterium celatum.

Mycobacterium celatum is a nontuberculous mycobacterium shown to cause symptoms similar to pulmonary M. tuberculosis. Certain strains have been shown to cross-react with the probes used to detect M. tuberculosis, making this a diagnostic challenge. We present a 56-year-old gentleman who developed signs and symptoms of lung infection with computed tomography scan of the chest showing right lung apex cavitation. Serial sputum samples were positive for acid-fast bacilli and nucleic acid amplification testing identified M. tuberculosis ribosomal RNA, resulting in treatment initiation. Further testing with high performance liquid chromatography showed a pattern consistent with M. celatum. This case illustrates the potential for M. celatum to mimic M. tuberculosis in both its clinical history and laboratory testing due to the identical oligonucleotide sequence contained in both. An increasing number of case reports suggest that early reliable differentiation could reduce unnecessary treatment and public health intervention associated with misdiagnosed tuberculosis.

Retroviral expression of MIR2 decreases both surface MHC class I and the alloimmune CTL response.

The immune response to allogeneic cells in tissue-engineered constructs is a major barrier to their successful application in the treatment of many human diseases. Specifically, the T cell-mediated immune response, initiated through the recognition of cell surface MHCI molecules, is the primary cause of acute cellular allograft rejection. In this study, we altered expression of MHCI through viral immunomodulatory mechanisms to examine whether allogeneic cells could be made to 'mimic' viral evasion of a host CTL response. We demonstrate the successful application of a retroviral vector in vitro to overexpress the Kaposi's sarcoma-associated herpesvirus immunomodulatory protein, MIR2, in human monocyte-like myeloid progenitor cells. This approach led to differential downregulation of cell surface MHCI, ICAM-1 and B7-2 molecules. We also demonstrate that downregulation of immunoactive molecules has the functional effect of significantly reducing T cell-mediated cytotoxicity without altering NK-mediated cytotoxicity in vitro. These results provide proof-of-concept that viral immune evasion strategies allow cell-based tissue-engineered constructs to delay or even prevent acute cellular immune rejection in vivo. Importantly, this methodology could facilitate the development of universal donor cells for tissue engineering applications.

Characterization of viability and proliferation of alginate-poly-L-lysine-alginate encapsulated myoblasts using flow cytometry.

Genetically modified cells encapsulated in alginate-poly-L-lysine-alginate (APA) are being developed to deliver therapeutic products to treat a variety of diseases. The characterization of the encapsulated cells thus becomes paramount. This study reports a novel method to assess the viability, granularity and proliferation of encapsulated cells based on flow cytometry. The in vitro viability of encapsulated G8 murine myoblasts secreting canine FVIII (cFVIII) measured by flow cytometry was comparable to the traditional trypan blue exclusion method and both correlated with cFVIII secretion levels. In contrast, after implantation into mice, only viability measured by flow cytometry correlated with cFVIII secretion. Further, flow cytometry analysis of encapsulated cells maintained in vitro and in vivo revealed a greater fraction of granular cells compared to free cells, suggesting that encapsulation influences the morphology (cytoplasmic composition) of cells within APA microcapsules. Interestingly, the proliferation study showed that encapsulated cells proliferate faster, on average, and were more heterogeneous in vivo compared to in vitro culture conditions, suggesting that encapsulated cell proliferation is complex and environment-dependent. In conclusion, we show that flow cytometry analysis allows for a more consistent and comprehensive examination of encapsulated cells to aid in the development of cell therapy protocols.