Characteristics of viral pneumonia in non-HIV immunocompromised and immunocompetent patients: a retrospective cohort study.

BACKGROUND: Concerning viral pneumonia, few large-scale comparative studies have been published describing non-HIV immunocompromised and immunocompetent patients, but the epidemiological characteristics of different viruses or underlying diseases in immunocompromised hosts are lacking. METHODS: We retrospectively recruited patients hospitalised with viral pneumonia from six academic hospitals in China between August 2016 and December 2019. We measured the prevalence of comorbidities, coinfections, nosocomial infections, and in-hospital mortalities. RESULTS: Of the 806 patients, 370 were immunocompromised and 436 were immunocompetent. The disease severity and in-hospital mortality of immunocompromised patients were higher than those of immunocompetent patients. During the influenza season, an increased number of cases of influenza virus (IFV) infection were found in the immunocompromised group, followed by cases of cytomegalovirus (CMV) and respiratory syncytial virus (RSV) infection. During the non-influenza season, CMV was the main virus detected in the immunocompromised group, while RSV, adenovirus (AdV), parainfluenza virus (PIV), and rhinovirus (HRV) were the main viruses detected in the immunocompetent group. Pneumonia caused by Pneumocystis jirovecii (22.4%), Aspergillus spp. (14.1%), and bacteria (13.8%) were the most frequently observed coinfections in immunocompromised patients but not in immunocompetent patients (Aspergillus spp. [10.8%], bacteria [7.1%], and Mycoplasma spp. [5.3%]). CMV infection and infection with two-or-more viruses were associated with a higher in-hospital mortality rate than non-IFV infection. However, patients with IFV and non-IFV infection in immunocompromised patients had similar disease severity and prognosis. CONCLUSIONS: Immunocompromised patients have a high frequency of coinfections, and a higher mortality rate was observed among those infected with CMV and two-or-more viruses. In addition, patients with IFV and non-IFV infection in immunocompromised patients had similar same disease severity and prognosis. The type of viral infection varied with seasons.

A pilot survey of ventilated cancer patients' perspectives and recollections of early mobility in the intensive care unit.

PURPOSE: To determine the level of recall, satisfaction, and perceived benefits of early mobility (EM) among ventilated cancer patients after extubation in the intensive care unit (ICU). METHODS: A survey of patients' perceptions and recollections of EM was administered within 72 h of extubation. Data on recall of EM participation, activities achieved, adequacy of staffing and rest periods, strength to participate, activity level of difficulty, satisfaction with staff instructions, breathing management, and overall rating of the experience were analyzed. The Confusion Assessment Method for ICU (CAM-ICU) was used for delirium screening. RESULTS: Fifty-four patients comprised the study group. Nearly 90% reported satisfaction with instructions, staffing, rest periods, and breathing management during EM. Participants indicated that EM maintained their strength (67%) and gave them control over their recovery (61%); a minority felt optimistic (37%) and safe (22%). Patients who achieved more sessions and "out-of-bed" exercises had better recall of actual activities compared with those who exercised in bed. Overall, patients with CAM-ICU-positive results (33%) performed less physical and occupational therapy exercises. CONCLUSIONS: Ventilated cancer patients reported an overall positive EM experience, but factual memory impairment of EM activities was common. These findings highlight the needs and the importance of shaping strategies to deliver a more patient focused EM experience.

Aerosol containment box to the rescue: extra protection for the front line.

As the COVID-19 pandemic has created shortages of vital personal protective equipment that threatens healthcare workers' risk of exposure, a need for innovative new ways to protect healthcare workers has emerged. An aerosol containment box that covers the patient's head and neck in bed provides a solution to protect clinicians during aerosol-generating procedures such as intubation. We collaborated with original designer HYL and modified the size to adapt to larger patients and operator mobility. We expand its applicability by allowing the use of different instruments. The container is outfitted with an ultra-low particulate air-equipped filtration vacuum device to create negative pressure within the chamber and actively remove floating droplet nuclei generated during a procedure. This barrier method will be a valuable and economical option to protect healthcare workers on the front line globally during this pandemic and beyond.

Comparative assessment of transient exposure of paclitaxel or zotarolimus on in vitro vascular cell death, proliferation, migration, and proinflammatory biomarker expression.

Both paclitaxel and zotarolimus are currently employed in vascular interventional therapies, such as drug-eluting stents, and are under investigation for use in other novel drug-device combination products. Paclitaxel is a microtubule-stabilizing compound with potent antiproliferative properties and antimigration effects, whereas zotarolimus is a potent mammalian target of rapamycin inhibitor with antiproliferative and antiinflammatory properties. This study was intended to compare paclitaxel and zotarolimus for intravascular applications in which drug exposure time may be reduced, such as in drug-coated balloons. These applications are generally aimed at reducing neointimal hyperplasia by limiting smooth muscle cell (SMC) proliferation and inflammatory cell recruitment, while minimally interfering with vessel reendothelialization after balloon denudation. In the cellular models described in this study, transient exposure of zotarolimus resulted in the sustained inhibition of SMC proliferation and reduced endothelial cell (EC) proinflammatory cytokine expression, while not affecting EC migration and viability. Transient exposure of paclitaxel inhibited SMC proliferation, EC migration, and overall cell viability, with no effect on expression of the proinflammatory biomarkers studied.

Characterization of vascular injury responses to stent insertion in an ex-vivo arterial perfusion model.

PURPOSE: To develop an ex-vivo arterial perfusion model to evaluate vascular responses to bare metal stents (BMS) and drug-eluting stents (DES) in porcine carotid arteries. MATERIALS AND METHODS: Porcine carotid arteries with BMS or DES were cultured under hemodynamic stimuli for 24 hours and 72 hours. Vascular responses of arteries with stents were assessed by cellular functionality and gene expression and compared with a noninjured (NI) control group at each time point. Cellular functionality was confirmed with sequential dosing of norepinephrine (NE), acetylcholine (ACH), and sodium nitroprusside (SNP). QuantiGene (Panomics, Fremont, California) branched DNA (bDNA) assay was used to evaluate gene expression of endothelial cell (EC) and smooth muscle cell (SMC) biomarkers and compare it with responses of in-vivo arteries with stents. Bromodeoxyuridine (BrDU) stain was also used to detect cellular proliferation in the ex-vivo arteries with stents. RESULTS: EC relaxation and SMC contraction in response to vasoactivators indicated the arteries remained viable and functional for at least 72 hours in culture. SMC-dependent contractility and EC-dependent relaxation were lower in arteries with stents compared with NI arteries. Greater SMC proliferation was observed in BMS arteries compared with DES arteries. Cellular proliferation, EC function, and SMC marker expression at acute time points were similar between both models suggesting that the ex-vivo arterial model can provide comparative predictions of stent injury in vivo. CONCLUSIONS: The ex-vivo arterial perfusion model can be used as a quick and less costly (than current in-vivo and some in-vitro perfusion testing models) approach for evaluating the vascular responses to various stent design parameters (eg, strut thickness, strut width).

New-Onset Seizures in Three COVID-19 Patients: A Case Series.

SUMMARY: Neurological manifestations of coronavirus disease 2019 most commonly present in severe cases and range from mild complications, such as headache and dizziness, to severe complications, such as encephalopathy and acute cerebrovascular disease. Seizures, however, are an underreported neurological manifestation of this disease. We present three critically ill coronavirus disease 2019 patients with EEG monitoring who developed new-onset seizures and encephalopathy up to three-and-a-half weeks after symptom onset. There are several speculated etiologies for the development of new-onset seizures; however, the pathogenic mechanism remains unknown. Testing of coronavirus disease 2019 in the cerebrospinal fluid in addition to extensive research on neurological manifestations is warranted.

Simulation and evaluation of the protective barrier enclosure for cardiopulmonary resuscitation.

INTRODUCTION: The COVID-19 pandemic has presented a significant challenge for infection prevention and control during airway management in anaesthesia and critical care. The protective barrier enclosure has been described and studied particularly for perioperative anaesthesia use. The potential use of the protective barrier enclosure during cardiopulmonary resuscitation has been poorly explored in the current literature. This work aims to demonstrate the potential of protective barrier enclosure in limiting aerosol dispersion during cardiopulmonary resuscitation delivery. METHODS: A proof-of-concept simulation study was conducted to evaluate the protective properties of the protective barrier enclosure during cardiopulmonary resuscitation. Aerosol was simulated using a fluorescent dye trapped within the manikin. Three different methods of cardiopulmonary resuscitation delivery with a protective barrier enclosure applied over the manikin's head were conducted. The first method simulated a chest compression only cardiopulmonary resuscitation, the second method also used chest compressions only, with a face mask fitted on the victim, while the third method, the victim was given chest compression and bag-valve-mask ventilation by two rescuers. RESULTS: In the first method, release of aerosol from the manikin's mouth was observed during chest compression, while in second method, most of the aerosol was trapped within the face mask, with only minor leaking. However, when bag-valve-mask ventilation was delivered, the aerosol leaked out at high speed around the bag-valve-mask seal. No aerosol condensation was found outside of the protective barrier enclosure in all scenes. CONCLUSION: Protective barrier enclosure may reduce aerosol exposure to the rescuers during out-of-hospital cardiac arrest.

Aetiology and prognostic risk factors of mortality in patients with pneumonia receiving glucocorticoids alone or glucocorticoids and other immunosuppressants: a retrospective cohort study.

OBJECTIVES: Long-term use of high-dose glucocorticoids can lead to severe immunosuppression and increased risk of treatment-resistant pneumonia and mortality. We investigated the aetiology and prognostic risk factors of mortality in hospitalised patients who developed pneumonia while receiving glucocorticoid therapy alone or glucocorticoid and other immunosuppressant therapies. DESIGN: Retrospective cohort study. SETTING: Six secondary and tertiary academic hospitals in China. PARTICIPANTS: Patients receiving glucocorticoids who were hospitalised with pneumonia between 1 January 2013 and 31 December 2019. MAIN OUTCOMES: We analysed the prevalence of comorbidities, microbiology, antibiotic susceptibility patterns, 30-day and 90-day mortality and prognostic risk factors. RESULTS: CONCLUSIONS: A total of 716 patients were included, with pneumonia pathogens identified in 69.8% of patients. Significant morbidities occurred, including respiratory failure (50.8%), intensive care unit transfer (40.8%) and mechanical ventilation (36%), with a 90-day mortality of 26.0%. Diagnosis of pneumonia occurred within 6 months of glucocorticoid initiation for 69.7% of patients with Cytomegalovirus (CMV) pneumonia and 79.0% of patients with Pneumocystis jirovecii pneumonia (PCP). Pathogens, including Pneumocystis, CMV and multidrug-resistant bacteria, were identified more frequently in patients with persistent lymphocytopenia and high-dose glucocorticoid treatment (≥30 mg/day of prednisolone or equivalent within 30 days before admission). The 90-day mortality was significantly lower for non-CMV viral pneumonias than for PCP (p<0.05), with a similar mortality as CMV pneumonias (24.2% vs 38.1% vs 27.4%, respectively). Cox regression analysis indicated several independent negative predictors for mortality in this patient population, including septic shock, respiratory failure, persistent lymphocytopenia, interstitial lung disease and high-dose glucocorticoid use.Patients who developed pneumonia while receiving glucocorticoid therapy experienced high rates of opportunistic infections, with significant morbidity and mortality. These findings should be carefully considered when determining treatment strategies for this patient population.

A Basic Therapy Gone Awry.

Baking soda (sodium bicarbonate) is a common household item that has gained popularity as an alternative cancer treatment. Some have speculated that alkali therapy neutralizes the extracellular acidity of tumor cells that promotes metastases. Internet blogs have touted alkali as a safe and natural alternative to chemotherapy that targets cancer cells without systemic effects. Sodium bicarbonate overdose is uncommon, with few reports of toxic effects in humans. The case described here is the first reported case of severe metabolic alkalosis related to topical use of sodium bicarbonate as a treatment for cancer. This case highlights how a seemingly benign and readily available product can have potentially lethal consequences.

Hemangioblastic characteristics of fetal bone marrow-derived Flk1(+)CD31(-)CD34(-) cells.

OBJECTIVE: To investigate whether Flk1(+)CD31(-)CD34(-) cells isolated from fetal bone marrow (BM) have characteristics of hemangioblasts, i.e., progenitors of endothelial and hematopoietic cells. MATERIALS AND METHODS: Mononuclear cells from fetal BM were negatively sorted by CD45, GlyA, and CD34 micromagnetic beads, then cultured to form cell colonies. A single colony was harvested. Culture-expanded cells were seeded on ECM gel or semisolid media supplemented with endothelial and hematopoietic growth factors, respectively. Immunochemistry staining and RT-PCR were performed for cell characterization. RESULTS: 99% of cells from the single colony maintained Flk1(+) and CD31/CD34(-) during passaging. On ECM gel, Flk1(+)CD31(-)CD34(-) cells could grow into vascular structure that was positive for CD31 and vWF. There were round CD34(+) cells around the vascular structure. When angiogenesis inhibitor suramin was added before tube formation, formation of vascular structure was blocked. Additionally, Flk1(+)CD31(-)CD34(-) cells cultured on hematopoietic condition could differentiate into hematopoietic cells which expressed GATA-1, 2, and gamma, beta globin gene. After being replated in methylcellulose medium, they formed typical erythroid colonies. CONCLUSIONS: Flk1(+)CD31(-)CD34(-) cells derived from fetal BM could differentiate into endothelial and hematopoietic cells. The results suggested that these Flk1(+)CD31(-)CD34(-) cells after embryo stage bear characteristics of hemangioblast and may have potential application for the hematopoietic and vascular diseases.

Transcatheter injection-induced changes in human bone marrow-derived mesenchymal stem cells.

Human mesenchymal stem cells (hMSC) are being administered by direct intramyocardial (IM) injection into patients with myocardial dysfunction with an objective to improve clinical status. However, surprisingly little attention has been directed to qualifying hMSC functionality beyond simple viability. In particular, the transit of hMSCs through a small-caliber needle lumen, the final fluidic pathway for all IM injection devices, may be especially prone to inducing unwarranted effects on cell function. This study evaluated the changes in clonogenicity, gene expression, and cytokine secretion that may be induced in hMSC (20 million/ml) by injection through a 26-gauge Nitinol needle at two different flow rates compared to noninjected control samples. Results indicated that hMSC viability and colony forming unit (CFU) formation was not altered by changes in injection rate, although a trend toward lower titers was noted at the higher flow rate, for the specific batch of hMSCs studied. The gene expression and cytokine analysis data suggest that delivering a suspension of MSCs through narrow lumen needles may marginally alter certain gene expression programs, but that such in vitro effects are transient and not translated into measurable differences in protein production. Gene expression levels of four cytokines (bFGF, SDF-1, SCF, VEGF) were significantly different at 400 microl/min, and that of all cytokines were significantly different at 1600 microl/min when compared to controls (p < 0.05). These changes were less pronounced (statistically insignificant for most cases, p > 0.05) and, in certain instances directionally opposite, at 72 h. However, no differences in the amounts of secreted bFGF, VEGF, or TGF-beta were detectable at either of the two time points or flow rates. We infer that intramyocardial administration by transcatheter techniques is unlikely to interfere with the machinery required for cell replication or secretion of regulatory and other growth factors, which are the mainstays of MSC contribution to cardiac tissue repair and regeneration.