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OBJECTIVE: To describe the impact of novel pH1N1 virus in Atlanta, GA, for inpatient and intensive care services, including lung lavage data and determinants of disease outcome, from the earliest group of infected US population after initial cases. DESIGN: An observational review of all patients with laboratory-confirmed pH1N1 disease hospitalized in four Atlanta hospitals from August 1 through October 31, 2009. Data reviewed included demographics, anthropometrics, clinical laboratory, and respiratory physiology. SETTING: Four hospitals in urban Atlanta, Georgia. PATIENTS: Consecutively admitted patients between August 1 and October 31, 2009 with laboratory confirmed pH1N1 infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 109 patients were admitted during the surveillance period and intensive care unit care was required in 23 patients (21%) among which there were six deaths (26%). Only eight of the 109 (7%) patients were without medical comorbidity; 34% of the 65 female patients were pregnant and none died or required intensive care unit care. Patients with respiratory failure undergoing bronchoalveolar lavage exhibited neutrophilic predominance (average 64%) and negative bacterial cultures. Body mass index was > 30 kg/m in 35 of 81 (43%) of patients with anthropometric data and 16 of 23 (70%) patients requiring intensive care unit care (p = .03). The 16 patients who required mechanical ventilation (70% of intensive care unit patients) were characterized by severe hypoxemia (requiring high levels of inspired oxygen and positive end-expiratory pressures), reduced lung compliance, and high lung injury scores. CONCLUSIONS: This first report of the second wave of US pH1N1 disease from Atlanta, GA, shares epidemiologic characteristics of earlier cohorts but differs by having an even greater prevalence of obesity and fewer patients who were free from chronic medical conditions. Importantly, lung lavage fluid in severe pH1N1 disease is predominantly neutrophilic and culture-negative. Further reports are needed to validate these new findings regarding pH1N1 disease in the United States. [ABSTRACT FROM AUTHOR]

Introduction: Numerous inflammatory markers may serve a role in prognostication of patients hospitalized with COVID-19 infection. Early in the pandemic, our health system created an admission order set which included daily d-dimer, c-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin. Given more available outcomes data, limiting standing order of labs that do not affect daily management could result in significant cost savings to the health system without adverse patient outcomes. The purpose of this study was to determine ordering and utilization patterns of inflammatory markers by physicians caring for patients hospitalized with COVID-19 infection., Methods: An anonymous 10-question survey was distributed to 125 physicians (Infectious Disease, Hospitalist, Pulmonary and Critical Care faculty). Responses were tallied and values greater than 50% were identified as the majority of the surveyed group., Results: Of the 125 physicians surveyed, 77 (62%) responded. A total of 57.1% (44/77) of physicians reported ordering daily inflammatory markers for 3 - 10 days from admission. Another 31.2% (24/77) ordered markers until clinical improvement or hospital discharge. D-dimer was used for care decisions by 83.1% (64/77) of respondents; 93.8% (60/64) of those reported utilizing it in determining anticoagulation dose. CRP was used by 61% (47/77) of physicians to help identify a secondary infection or determine steroid dose or duration. LDH and ferritin were not used for management decisions by the majority of physicians. Inflammatory markers were not used routinely after isolation precautions had been discontinued, even when ongoing care required mechanical ventilation., Conclusions: Of the markers studied, both d-dimer and CRP were considered useful by most respondents. LDH and ferritin were used less frequently and were not considered as useful in guiding medical decision making. Discontinuation of standing daily LDH and ferritin orders is believed to have potential to result in cost savings to the health care system with no adverse patient outcomes., (© 2022 The University of Kansas Medical Center.)

Despite widespread public health concern regarding opioid misuse and overuse, there is a paucity of literature on the acute and chronic pulmonary vascular and cardiac implications of excipient lung disease. This case series describes the clinical presentation of five adult patients who experienced profound pulmonary hypertension and right heart failure in the setting of confirmed or suspected crushed opioid injection at a single academic center between 2012 and 2019. The clinical characteristics and right heart catheterization data presented in these cases demonstrate the acute intravascular effects of the intravenous injection of crushed opioids and potential for hemodynamic collapse. Moreover, these cases suggest that survivors of acute excipient lung disease may develop chronic pulmonary vascular disease. Further studies are needed to explore the epidemiology and outcomes of oral opioid-induced intravascular excipient lung disease to increase awareness of this life-threatening complication among health care professionals and guide treatment and prevention measures., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, aka COVID-19) virus has evolved into a World Health Organization-declared pandemic which has strained our regional critical care and hospital resources., Methods: A Critical Care Task Force was established between Kansas City area intensive care units to allow for preparedness for potential surges by sharing of bed capacity both in the ICU and hospital, and ventilator capacity as well as weekly web-based meetings to share resource concerns and best practice. This Task Force also collected patient information to understand the dynamics of community impact and resource needs better. This effort allowed for compilation and dissemination of information regarding data that describe characteristics of patients with COVID-19 compared to a random sample of medical ICU patients with conditions other than COVID-19.Demographic and therapeutic factors affecting patients admitted to medical intensive care units in the Kansas City metro area are reported from May 5, 2020 until June 2, 2020 using a retrospective case-control study examining gender, race, and therapeutic options including modes of ventilation, vasopressor requirements, renal-replacement therapy, and disposition., Results: During data collection, patients being treated for COVID-19 in intensive care units in the Kansas City metropolitan area were more likely to be older, less likely to be white, and less likely to be immunosuppressed as compared to those being treated for non-COVID illnesses. They were more likely to require non-invasive ventilation and undergo prone positioning but were equally likely to require invasive ventilation and other organ supportive therapy., Conclusions: Hospitalized patients being treated for COVID-19 in the Kansas City metropolitan area have similar demographics to those being reported in the U.S. including age and race. Additionally, establishing a Critical Care Task Force in response to the pandemic allowed for preparation for a potential surge, establishing capacity, and disseminating timely information to policy makers and critical care workers on the front line., (© 2021 The University of Kansas Medical Center.)

Rationale: Coronavirus disease 2019 (COVID-19) can cause disruption of the renin-angiotensin system in the lungs, possibly contributing to pulmonary capillary leakage. Thus, angiotensin receptor blockers (ARBs) may improve respiratory failure. Objective: Assess safety of losartan for use in respiratory failure related to COVID-19 (NCT04335123). Methods: Single arm, open label trial of losartan in those hospitalized with respiratory failure related to COVID-19. Oral losartan (25 mg daily for 3 days, then 50 mg) was administered from enrollment until day 14 or hospital discharge. A post-hoc external control group with patients who met all inclusion criteria was matched 1:1 to the treatment group using propensity scores for comparison. Measures: Primary outcome was cumulative incidence of any adverse events. Secondary, explorative endpoints included measures of respiratory failure, length of stay and vital status. Results: Of the 34 participants enrolled in the trial, 30 completed the study with a mean age SD of 53.8 ± 17.7 years and 17 males (57%). On losartan, 24/30 (80%) experienced an adverse event as opposed to 29/30 (97%) of controls, with a lower average number of adverse events on losartan relative to control (2.2 vs. 3.3). Using Poisson regression and controlling for age, sex, race, date of enrollment, disease severity at enrollment, and history of high-risk comorbidities, the incidence rate ratio of adverse events on losartan relative to control was 0.69 (95% CI: 0.49-0.97) Conclusions: Losartan appeared safe for COVID-19-related acute respiratory compromise. To assess true efficacy, randomized trials are needed., Competing Interests: CB reported receiving grant support from the NIH National Center for Advancing Translational Sciences (NCATS) and Cystic Fibrosis Foundation (CFF) during the conduct of the study. NB reported receiving grant support from the NIH National Institute of Neurologic Disease and Stroke during the conduct of the study. MC reported receiving University grant support from the NIH, American Lung Association and PCORI; pharmaceutical grant support from AstraZeneca, GSK, Novartis, Pulmatrix, Sanofi-Aventis and Shinogi; is a consult for Genentech, Teva, Sanofi-Aventis and Novartis; is a speaker for AstraZeneca, Genentech, GSK, Regeneron, Sanofi and Teva; receives royalties from Elsevier – all unrelated to the conduct of this study. MS reported receiving grant support from the NIH NHLBI, James and Ester King Biomedical Research Program, FAMRI and CFF during the conduct of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bengtson, Montgomery, Nazir, Satterwhite, Kim, Bahr, Castro, Baumlin and Salathe.)

Background: Serum lactate and central venous oxygen saturation (ScvO 2 ) are commonly used and commonly recommended as markers of tissue oxygenation in shock states. Medical literature has both explicitly stated and implied that the two biomarkers are interchangeable in the management of patients with shock. However, there have been relatively few direct comparisons of these tests in clinical circumstances, and the relationship between them is uncertain. The objective of our study was to evaluate whether simultaneous or near-simultaneous measurements of lactate and ScvO 2 reveal a consistent relationship between these two biomarkers., Methods: A retrospective cohort study was conducted in an urban, academic US hospital. All adults in ICUs between March 2007 and March 2017 who had a lactate measurement and ScvO 2 or mixed venous oxygen saturation (SvO 2 ) measurement made +/- 1 h from the lactate were included. Linear and non-linear correlations of ScvO 2 and lactate were assessed in a variety of shock states., Results: Two thousand sixty-two patients were included. Lactate and ScvO 2 correlated poorly ( r 2  = 0.0041, p  = 0.0019). This was true for patients with ScvO 2 ≤ 65% ( r 2  = 0.0431, p  < 0.001), patients with normal kidney and liver function ( r 2  = 0.0517, p  < 0.001), and septic shock patients ( r 2  = 0.0037, p  = 0.17). For patients with an O 2 extraction ratio ≥ 50%, lactate and ScvO 2 were strongly correlated ( r 2  = 0.93, p  = 0.0019), but these patients represented only 2.8% of patients in whom the ratio could be calculated., Conclusions: Lactate can predict ScvO 2 when patients are at or below the critical oxygen delivery threshold, but relatively few shock patients meet this criterion. In the overall population of critically ill patients, serum lactate predicts ScvO 2 poorly, even after controlling for factors that may affect lactate production. Lactate and ScvO 2 should not be assumed to be interchangeable markers of tissue oxygenation/perfusion., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

To determine whether stroke volume (SV) guided fluid resuscitation in patients with severe sepsis and septic shock alters Intensive Care Unit (ICU) fluid balance and secondary outcomes, this retrospective cohort study evaluated consecutive patients admitted to an ICU with the primary diagnosis of severe sepsis or septic shock. Cohorts were based on fluid resuscitation guided by changes in SV or by usual care (UC). The SV group comprised 100 patients, with 91 patients in the UC group. Net fluid balance for the ICU stay was lower in the SV group (1.77L) than in the UC group (5.36L) (p=0.022). ICU length of stay was 2.89days shorter (p=0.03) and duration of vasopressors was 32.8h less (p=0.001) in the SV group. SV group required less mechanical ventilation (RR, 0.51; p=0.0001). The SV group was less likely to require acute hemodialysis (6.25%) compared with the UC group (19.5%) (RR, 0.32; p=0.01). In multivariable analysis, SV was an independent predictor of lower fluid balance, LOS, time on vasopressors, and not needing mechanical ventilation. This study demonstrated that SV guided fluid resuscitation in patients with severe sepsis and septic shock was associated with reduced fluid balance and improved secondary outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Post-ICU Syndromes (PICS) remain a devastating problem for intensive care unit (ICU) survivors. It is currently unknown if de novo initiation of an antidepressant medication during ICU stay decreases the prevalence of post-ICU depression. We performed a retrospective, pilot study evaluating patients who had not previously been on an antidepressant medication and who were started on an antidepressant while in the trauma surgical, cardiothoracic, or medical intensive care unit (ICU). The PHQ-2 depression scale was used to ascertain the presence of depression after ICU discharge and compared this to historical controls. Of 2,988 patients admitted to the ICU, 69 patients had de novo initiation of an antidepressant medication and 27 patients were alive and available for study inclusion. We found the prevalence of depression in these patients to be 26%, which is not statistically different than the prevalence of post-ICU depression in historical controls [95% CI (27.6%, 51.6%)]. De novo initiation of an antidepressant medication did not substantially decrease the prevalence of post-ICU depression in this retrospective, pilot study.

Rationale: The patterns and outcomes of noninvasive, positive-pressure ventilation (NIPPV) use in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (COPD) nationwide are unknown., Objectives: To determine the prevalence and trends of noninvasive ventilation for acute COPD., Methods: We used data from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample to assess the pattern and outcomes of NIPPV use for acute exacerbations of COPD from 1998 to 2008., Measurements and Main Results: An estimated 7,511,267 admissions for acute exacerbations occurred from 1998 to 2008. There was a 462% increase in NIPPV use (from 1.0 to 4.5% of all admissions) and a 42% decline in invasive mechanical ventilation (IMV) use (from 6.0 to 3.5% of all admissions) during these years. This was accompanied by an increase in the size of a small cohort of patients requiring transition from NIPPV to IMV. In-hospital mortality in this group appeared to be worsening over time. By 2008, these patients had a high mortality rate (29.3%), which represented 61% higher odds of death compared with patients directly placed on IMV (95% confidence interval, 24-109%) and 677% greater odds of death compared with patients treated with NIPPV alone (95% confidence interval, 475-948%). With the exception of patients transitioned from NIPPV to IMV, in-hospital outcomes were favorable and improved steadily year by year., Conclusions: The use of NIPPV has increased significantly over time among patients hospitalized for acute exacerbations of COPD, whereas the need for intubation and in-hospital mortality has declined. However, the rising mortality rate in a small but expanding group of patients requiring invasive mechanical ventilation after treatment with noninvasive ventilation needs further investigation.

Background: Continuous insulin infusion (CII) to manage hyperglycemia is the accepted standard of care in the intensive care unit (ICU); however, the safety and efficacy of CII in the non-ICU setting has not been determined., Research Design and Methods: This is a retrospective analysis of 200 consecutive patients receiving CII while admitted to general medical-surgical units at Emory University Hospital. We evaluated clinical outcomes and rates of hyperglycemia (blood glucose [BG] >200 mg/dL) and hypoglycemia (BG <60 mg/dL) events during CII., Results: A total of 200 patients (age 52 +/- 16 years; male/female [M/F] 108/92) were admitted to general medicine (45%) or surgery (55%) services, 88.5% with history of diabetes and 41% treated with corticosteroids. The mean BG prior to and during the CII was 323 mg/dL and 170 mg/dL, respectively. Blood glucose of

A novel cell culture methodology is described in which diffusion tensor magnetic resonance imaging (DTMRI) and cell micropatterning are combined to fabricate cell monolayers that replicate realistic cross-sectional tissue structure. As a proof-of-principle, neonatal rat ventricular myocyte (NRVM) monolayers were cultured to replicate the tissue microstructure of murine ventricular cross-sections. Specifically, DTMRI-measured in-plane cardiac fiber directions were converted into soft-lithography photomasks. Silicone stamps fabricated from the photomasks deposit fibronectin patterns to guide local cellular alignment. Fibronectin patterns consisted of a matrix of 190 microm(2) subregions, each comprised of parallel lines 11-20 microm-wide, spaced 2-8.5 microm apart, and angled to match local DTMRI-measured fiber directions. Within 6 days of culture, NRVMs established confluent, electrically coupled monolayers, and for 18 microm-wide, 5 microm-spaced lines, directions of cell alignment in subregions microscopically replicated DTMRI-measurements with a local error of 7.2 +/- 4.1 degrees . By adjusting fibronectin line widths and spacings, cell elongation, gap junctional membrane distribution, and local cellular disarray were altered without changing the dominant directions of cell alignment in individual subregions. Changes in the anisotropy of electrical propagation were assessed by optically mapping membrane potentials. This novel methodology is expected to enable systematic studies of intramural structure-function relationships in both healthy and structurally remodeled hearts.

Introduction: Current management of posttraumatic stress disorder (PTSD) focuses on the psychiatric parameters of this condition. Little has been written about co-morbid overweight and obesity in PTSD., Methods: We used the database of the recently constituted PTSD program at the Hunter Holmes McGuire Veterans Affairs Medical Center in Richmond, Virginia to assess and better understand the prevalence and severity of overweight and obesity among military veterans with PTSD. Variables assessed included age, decade of life, height, weight, sex, race, and severity and chronicity of PTSD. We used PTSD CheckList-Military Version (PCL-M) to assess current complaints and service-connected disability (SCD) to estimate the long-term severity of PTSD., Results: Of the 221 male veterans extracted from our PTSD database for purposes of this study, 144 (65.2%) were in the age range of 50 to 59 years consistent with Vietnam veterans dominating our study population. Their mean body mass index (BMI) was 30.2+/-5.8 kg/m(2) placing the typical veteran in the obese range. Far exceeding the current US population rate of 64.5%, 82.8% of our study population was either overweight or obese. Our sample had BMI measurements greater than those reported for non-PTSD veterans and also BMI measurements reported in the literature for veterans with PTSD. Current (PCL-M) and long-term (SCD) markers of PTSD did not relate to obesity., Conclusions: The prevalence of overweight and obesity among our veterans with PTSD far exceeded current US population findings and those of other veteran groups with and without PTSD. PTSD symptoms, whether assessed acutely or chronically, did not explain our findings. Prospective studies of PTSD and comorbidity are needed using larger study populations to better understand the relationships among PTSD, stress, and obesity.

Introduction: We looked at the relationships among posttraumatic stress disorder (PTSD), body mass index (BMI) and socioeconomic status (SES) in a newly formed PTSD program at the Hunter Holmes McGuire Veterans Affairs Medical Center in Richmond, VA., Methods: We reviewed 265 records and then selected only black and white male veterans (n=252) for study. Variables were: 1) age, 2) decade of life, 3) height, 4) weight, 5) sex, 6) race, and 7) SES (estimated using priority group status). Low income is an important variable determining priority group status., Results: About two-thirds of the veterans were in the age range of 50-59 years (Vietnam veterans). Their mean BMI was 30.2 +/- 5.6 kg/m2, and this value did not separate by race. Far exceeding national numbers, 84.1% of our veterans were either overweight or obese. Veterans in the lower priority groups had greater (p=0.029) BMIs than their counterparts in higher priority groups., Conclusions: The pervasiveness of overweight and obesity in our PTSD population was profound. Our observations suggest that low SES is a likely contributor to veterans in lower priority groups having greater BMIs than veterans in higher priority groups.

Infective endocarditis caused by Proteus mirabilis is rare and is fatal in most cases. A case of a 64-year-old man presenting with fever, dysuria, and murmur is reported. P mirabilis endocarditis was diagnosed based on clinical presentation, blood culture findings, and the presence of a large mitral valve vegetation seen on echocardiogram. The patient survived after long-term antibiotics and surgical replacement of the mitral valve. The clinical characteristics and complications from reported cases of P mirabilis endocarditis are reviewed.

The budding yeast shmoo tip is a model system for analyzing mechanisms coupling force production to microtubule plus-end polymerization/depolymerization. Dynamic plus ends of astral microtubules interact with the shmoo tip in mating yeast cells, positioning nuclei for karyogamy. We have used live-cell imaging of GFP fusions to identify proteins that couple dynamic microtubule plus ends to the shmoo tip. We find that Kar3p, a minus end-directed kinesin motor protein, is required, whereas the other cytoplasmic motors, dynein and the kinesins Kip2p and Kip3p, are not. In the absence of Kar3p, attached microtubule plus ends released from the shmoo tip when they switched to depolymerization. Furthermore, microtubules in cells expressing kar3-1, a mutant that results in rigor binding to microtubules [2], were stabilized specifically at shmoo tips. Imaging of Kar3p-GFP during mating revealed that fluorescence at the shmoo tip increased during periods of microtubule depolymerization. These data are the first to localize the activity of a minus end-directed kinesin at the plus ends of microtubules. We propose a model in which Kar3p couples depolymerizing microtubule plus ends to the cell cortex and the Bim1p-Kar9p protein complex maintains attachment during microtubule polymerization. In support of this model, analysis of Bim1p-GFP at the shmoo tip results in a localization pattern complementary to that of Kar3p-GFP.

Mutants of the yeast Kar3 protein are defective in nuclear fusion, or karyogamy, during mating and show slow mitotic growth, indicating a requirement for the protein both during mating and in mitosis. DNA sequence analysis predicts that Kar3 is a microtubule motor protein related to kinesin, but with the motor domain at the C-terminus of the protein rather than the N-terminus as in kinesin heavy chain. We have expressed Kar3 as a fusion protein with glutathione S-transferase (GST) and determined the in vitro motility properties of the bacterially expressed protein. The GST-Kar3 fusion protein bound to a coverslip translocates microtubules in gliding assays with a velocity of 1-2 microns/min and moves towards microtubule minus ends, unlike kinesin but like kinesin-related Drosophila ncd. Taxol-stabilized microtubules bound to GST-Kar3 on a coverslip shorten as they glide, resulting in faster lagging end, than leading end, velocities. Comparison of lagging and leading end velocities with velocities of asymmetrical axoneme-microtubule complexes indicates that microtubules shorten preferentially from the lagging or minus ends. The minus end-directed translocation and microtubule bundling of GST-Kar3 is consistent with models in which the Kar3 protein crosslinks internuclear microtubules and mediates nuclear fusion by moving towards microtubule minus ends, pulling the two nuclei together. In mitotic cells, the minus end motility of Kar3 could move chromosomes polewards, either by attaching to kinetochores and moving them polewards along microtubules, or by attaching to kinetochore microtubules and pulling them polewards along other polar microtubules.(ABSTRACT TRUNCATED AT 250 WORDS)

The Kar3 protein (Kar3p), a protein related to kinesin heavy chain, and the Cik1 protein (Cik1p) appear to participate in the same cellular processes in S. cerevisiae. Phenotypic analysis of mutants indicates that both CIK1 and KAR3 participate in spindle formation and karyogamy. In addition, the expression of both genes is induced by pheromone treatment. In vegetatively growing cells, both Cik1::beta-gal and Kar3::beta-gal fusions localize to the spindle pole body (SPB), and after pheromone treatment both fusion proteins localize to the spindle pole body and cytoplasmic microtubules. The dependence of Cik1p and Kar3p localization upon one another was investigated by indirect immunofluorescence of fusion proteins in pheromone-treated cells. The Cik1p::beta-gal fusion does not localize to the SPB or microtubules in a kar3 delta strain, and the Kar3p::beta-gal fusion protein does not localize to microtubule-associated structures in a cik1 delta strain. Thus, these proteins appear to be interdependent for localization to the SPB and microtubules. Analysis by both the two-hybrid system and co-immunoprecipitation experiments indicates that Cik1p and kar3p interact, suggesting that they are part of the same protein complex. These data indicate that interaction between a putative kinesin heavy chain-related protein and another protein can determine the localization of motor activity and thereby affect the functional specificity of the motor complex.

The last year has seen dramatic progress in the use of genetic and biochemical approaches to identify microtubule-organizing center components. The use of vertebrate and invertebrate egg extracts has allowed the development of novel assays for centrosome duplication and activation. A variety of mutations in fungi are being used to sort out the pathway of spindle pole body duplication.