The Diagnostic Yield of Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA) in Respiratory Compromised Patients under General Anesthesia.

BACKGROUND: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a frequently used method for obtaining tissue samples for the diagnosis of various respiratory conditions, including lung cancer staging. In most cases, EBUS-TBNA is performed under moderate sedation (MS). However, in cases of respiratory compromised patients, if this procedure is performed, it is conducted under general anesthesia (GA). OBJECTIVES: To assess the diagnostic yield of EBUS-TBNA among respiratory compromised patients. METHODS: Data of consecutive patients (n=191) who underwent EBUS-TBNA at our medical center between January 2019 and December 2019 were retrospectively analyzed. Respiratory compromised patients underwent GA and patients without respiratory compromise were mostly moderately sedated (MS). Characteristics, diagnostic yield, and complication rates were compared. RESULTS: Diagnostic yield was similar between the two sedation modes (89% in GA group and 78% in the MS group, P = 0.11). The number of total samples obtained per procedure was significantly higher in the GA vs. the MS group (4.1 ± 2.1 vs. 2.1 ± 1.33, P < 0.01). The overall complication rate was 13% and 20.9% in the GA vs. the MS groups, respectively (P = 0.14), with the most frequent complication being minor bleeding. Interestingly, while the number of brushings, bronchoalveolar lavage, and endobronchial biopsy were similar, the percent of subjects who underwent transbronchial biopsy was significantly higher in the GA group (49% vs. 24.2%, P < 0.01). CONCLUSIONS: EBUS-TBNA performed under GA among respiratory compromised patients is safe and has similar diagnostic yield to that of patients without a respiratory compromise.

The Profile of COPD Patients with Prolonged Hospitalizations: A Retrospective Analysis of 200 Hospital Admissions.

BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD) experience frequent exacerbations and need to be hospitalized, resulting in an economic and social burden. Although data exist regarding reasons of frequent hospitalizations, there is no data available about the impact on the length of stay (LOS). OBJECTIVES: To characterize the causes of prolonged hospitalizations in COPD patients. METHODS: A retrospective study was conducted of patients who were diagnosed and treated in the pulmonary department for severe COPD exacerbations. All patient demographic data and medical history were collected. Data regarding the disease severity were also collected (including Global Initiative for Obstructive Lung Disease [GOLD] criteria, pulmonologist follow-up, prior hospitalizations, and LOS). RESULTS: The study comprised 200 patients, average age 69.5 ± 10.8 years, 61% males. Of these patients, 89 (45%) were hospitalized for up to 4 days, 111 (55%) for 5 days or more, and 34 (17%) for more than 7 days. Single patients had longer LOS compared with married patients (48% vs. 34%, P = 0.044). Multivariate analysis showed that the number of prior hospital admissions in the last year was a predictor of LOS (P = 0.038, odds ratio [OR] = 0.807, 95% confidence interval [95%CI] = 0.659-0.988), as well as the use of non-invasive respiratory support by bilevel positive airway pressure (BiPAP) during the hospitalization (P = 0.024, OR = 4.662, 95%CI = 1.229-17.681). CONCLUSIONS: Fewer previous hospitalizations due to COPD exacerbations and the need for non-invasive respiratory support by BiPAP were found as predictors of longer LOS.

Compassionate use of convalescent plasma for treatment of moderate and severe pneumonia in COVID-19 patients and association with IgG antibody levels in donated plasma.

BACKGROUND: We assessed outcome of patients with moderate and severe COVID-19 following treatment with convalescent plasma (CP) and the association with IgG levels in transfused CP. METHODS: A prospective cohort study. Primary outcome was improvement at day 14 defined as alive, not on mechanical ventilation, and moderate, mild, or recovered from COVID-19. Antibody levels in CP units were unknown at the time of treatment. IgG against the spike protein S1 was subsequently measured by ELISA. Neutralizing antibodies titers were determined in a subset. Outcome was assessed in relation to the mean antibody level transfused to the patients (≤4.0 versus >4.0). FINDINGS: Of 49 patients, 11 (22.4%) had moderate, 38 (77.6%) had severe disease, 28 were ventilated. At day 14, 24 (49.0%) patients improved, 9 (18.4%) died, and 13 (26.5%) were ventilated. In 14/98 (14.3%) CP units IgG was < 1.1 (cutoff calibration) and in 60 (61.2%) ≤4.0. IgG level and neutralizing antibody titer were correlated (0.85 p < 0.001). In patients receiving ≤4.0 antibody levels, 11/30 improved (36.7%) versus 13/19 (68.4%) in patients receiving >4.0 odds ratio (OR) 0.267 [95% confidence interval (CI) 0.079-0.905], P = 0.030. In patients diagnosed >10 days prior to treatment, 4/14 (22.4%) improved in the ≤4.0 antibody group, versus 6/7 (85.7%) in the >4.0 antibody group, OR 0.048 (95% CI, 0.004-0.520), P = 0.007. No serious adverse events were reported. INTERPRETATION: Treatment with CP with higher levels of IgG against S1 may benefit patients with moderate and severe COVID-19. IgG against S1 level in CP predicts neutralization antibodies titers.

Clinical Course and Outcomes of Severe Covid-19: A National Scale Study.

Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined. METHODS: This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality. RESULTS: This study included 156 patients (median age = 72 years (range = 22-97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0-37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84-0.96) were independent prognostic factors. CONCLUSIONS: In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.

Computed Tomography Angiography Findings in Pulmonary Embolism Patients Vary Following Thrombolytic Treatment.

BACKGROUND: Pulmonary embolism (PE) is the third most frequently occurring cardiovascular disease. However, the clinical presentation in patients with PE is variable. OBJECTIVES: To evaluate the prevalence of radiological findings detected in contrast-enhanced computed tomography angiography (CTA) and their significance in patients with PE; and to assess whether the CTA findings differed in patients receiving tissue plasminogen activator (tPA) therapy from those who did not. METHODS: We retrospectively reviewed CTA scans of 186 patients diagnosed with acute PE. Incidental findings on CTA scan were assessed, including mediastinal and parenchymal lymph nodes, pleural effusion, space-occupying lesions, consolidations, emphysema, and pericardial effusion. RESULTS: Patients receiving tPA (19.9%) were less likely to have pleural effusion (29.7% vs. 50.3%, P = 0.024). Other CTA findings did not differ between the tPA and non-tPA groups, including lung infiltrates (40.5% vs. 38.9, P = 0.857), space-occupying lesions (5.4% vs. 6.7%, P = 1), pericardial effusion (8.1% vs. 8.7%, P = 1), emphysema (21.6% vs. 17.4%, P = 0.557), lung (18.9% vs. 24.2%, P = 0.498), and mediastinal ( 24.3% vs. 25.5%, P = 0.883) lymph nodes, respectively. CONCLUSIONS: The prevalence of pleural effusion (unilateral or bilateral) was higher in patients not treated with tPA. Therefore, in patients with a borderline condition, the presence of pleural effusion could support the decision not to give tPA treatment.

Acute Infection in Ventilated Patients in the Intensive Care Unit: Association Between Resting Energy Expenditure and C-Reactive Protein.

BACKGROUND: Sepsis is a common cause of hospitalization, particularly in intensive care units (ICUs), and is a major cause of morbidity and mortality. Diagnosis is often difficult due to the absence of characteristic clinical signs (e.g., fever and leukocytosis); therefore, additional markers, in addition to C-reactive protein (CRP) and white blood cell (WBC) count, are needed. OBJECTIVES: To prospectively link resting energy expenditure (REE) with CRP, WBC count, and sequential organ failure assessment (SOFA) scores in ICU patients. Such a correlation may suggest REE measurement as an additional parameter for sepsis diagnosis. METHODS: Our study comprised 41 ventilated consecutive patients > 18 years of age. Patient demographic data, height, actual body weight, and SOFA scores were collected at admission. REE was measured by indirect calorimetry. REE, CRP, and WBC measurements were collected at admission, on day three after admission, and 1 week later or as clinically indicated. RESULTS: Comparison of the REE and CRP changes revealed a significant correlation between REE and CRP changes (r = 0.422, P = 0.007). In addition, CRP changes also correlated with the changes in REE (r = 0.36, P = 0.02). Although no significant correlations in REE, WBC count, and SOFA score were found, a significant trend was observed. CONCLUSIONS: To the best of our knowledge, this is the first study to link REE and CRP levels, indicative of severe infection. Further study is needed to establish these findings.

In-band optical signal-to-noise ratio monitoring technique based on Brillouin fiber ring laser.

We propose an improved technique for in-band optical signal-to-noise ratio (OSNR) monitoring based on a Brillouin fiber ring laser seeded by the optical channel to be monitored. This technique shows a reduction of the required input power into the monitor along with a large and tunable dynamic OSNR monitoring range. It is demonstrated experimentally and numerically for various bit rates and modulation formats.

Predictors of mortality of mechanically ventilated patients in internal medicine wards.

PURPOSE: Budget restrictions have led to shortage of intensive care unit (ICU) beds in several countries. Consequently, ventilated patients are often kept on the wards. This study examined survival likelihood among patients ventilated on the wards and the predictive value of commonly used severity-of-illness scores. METHODS: This study is a prospective observation and characterization of consecutive, mechanically ventilated patients in 3 internal medicine wards of a single hospital who were denied ICU admission. Outcome measures are as follows: 28-day mortality, survival to hospital discharge, and 3 months postdischarge. RESULTS: Eighty-six patients were examined. The patients were 78.9 ± 8.9 years old; 53% were independent preadmission. Respiratory insufficiency due to infection was the main reason for mechanical ventilation (58%). Charlson and acute physiology scores (APS) averaged 4 ± 2.2 and 91.8 ± 26.7, respectively. Twenty-eight-day mortality was 71%, whereas in-hospital mortality was 74% and 3 months postdischarge mortality was 79%. Survivors were significantly younger than nonsurvivors (74.4 ± 8.5 years vs 80.4 ± 8.6 years, P < .01), were more likely to be ventilated for cardiac causes (41% vs 11%, P = .04), and had significantly higher initial mean blood pressure (79.4 mm Hg vs 58.2 mm Hg, P = .02) and blood albumin levels (29.8 g/L vs 25.7 g/L, P = .05). Death rate was 10 times more likely, with an APS greater than 90 on the day of intubation as compared with an APS less than 90. CONCLUSION: Mortality in patients ventilated on the ward was high, especially in the subgroup of patients with an APS score greater than 90. The early calculation of APS may assist in focusing therapeutic efforts on patients with better survival chances.

Stimulated Brillouin scattering based in-band OSNR monitoring technique for 40 Gbps and 100 Gbps optical transparent networks.

We demonstrate experimentally and numerically that the SBS based in-band OSNR monitoring technique can be used for dual polarization signals. We also present novel approach for a drastic enhancement of the sensitivity monitoring range by intentionally adding in-band ASE noise into the signal. Numerical results are provided for 44.6 Gbps DPSK, 44.6 Gbps DQPSK and 112 Gbps Dual Polarization (DP-) QPSK signals, with both 100 GHz and 50 GHz channel spacing scenarios.

Computerized lung acoustic monitoring can help to differentiate between various chest radiographic densities in critically ill patients.

BACKGROUND: Complementary bedside lung monitoring modalities are often sought in order to assist in the differentiation between several lung opacities in the intensive care unit (ICU). OBJECTIVES: To evaluate the use of computerized lung acoustic monitoring as a complementary approach in the differentiation between various chest radiographic densities in critically ill patients. METHODS: Lung vibration intensity was assessed in 82 intensive care patients using vibration response imaging. Patients were classified according to their primary findings on chest radiography (CXR): consolidation (n = 35), congestion (n = 10), pleural effusion (n = 15), atelectasis/hypoinflation (n = 10) and normal findings (n = 12). Sixty patients were mechanically ventilated and 22 patients were spontaneously breathing. RESULTS: Significantly elevated vibration intensity was detected in patients with consolidation, as opposed to pleural effusion, atelectasis and normal CXR (p < 0.01, Mann-Whitney U test). Vibration intensity was also increased for congestion, but this increase was not significant. The positive predictive value of CXR lung opacity in combination with increased vibration intensity to detect consolidations and/or congestions was 95% (20/21). Furthermore, vibration intensity was significantly higher in mechanically ventilated patients compared to spontaneously breathing patients (p = 0.001, Mann-Whitney U test). Differences related to gender, age and body position were not significant. CONCLUSIONS: Computerized lung acoustic monitoring at the bedside was found to be a useful, readily available, noninvasive, adjunctive tool in the differentiation between various CXR densities in critically ill patients.

Changes in regional distribution of lung sounds as a function of positive end-expiratory pressure.

INTRODUCTION: Automated mapping of lung sound distribution is a novel area of interest currently investigated in mechanically ventilated, critically ill patients. The objective of the present study was to assess changes in thoracic sound distribution resulting from changes in positive end-expiratory pressure (PEEP). Repeatability of automated lung sound measurements was also evaluated. METHODS: Regional lung sound distribution was assessed in 35 mechanically ventilated patients in the intensive care unit (ICU). A total of 201 vibration response imaging (VRI) measurements were collected at different levels of PEEP between 0 and 15 cmH2O. Findings were correlated with tidal volume, oxygen saturation, airway resistance, and dynamic compliance. Eighty-two duplicated readings were performed to evaluate the repeatability of the measurement. RESULTS: A significant shift in sound distribution from the apical to the diaphragmatic lung areas was recorded when increasing PEEP (paired t-tests, P < 0.05). In patients with unilateral lung pathology, this shift was significant in the diseased lung, but not as pronounced in the other lung. No significant difference in lung sound distribution was encountered based on level of ventilator support needed. Decreased lung sound distribution in the base was correlated with lower dynamic compliance. No significant difference was encountered between repeated measurements. CONCLUSIONS: Lung sounds shift towards the diaphragmatic lung areas when PEEP increases. Lung sound measurements are highly repeatable in mechanically ventilated patients with various lung pathologies. Further studies are needed in order to fully appreciate the contribution of PEEP increase to diaphragmatic sound redistribution.

Small molecule activator of the human epithelial sodium channel.

The epithelial sodium channel (ENaC), a heterotrimeric complex composed of alpha, beta, and gamma subunits, belongs to the ENaC/degenerin family of ion channels and forms the principal route for apical Na(+) entry in many reabsorbing epithelia. Although high affinity ENaC blockers, including amiloride and derivatives, have been described, potent and specific small molecule ENaC activators have not been reported. Here we describe compound S3969 that fully and reversibly activates human ENaC (hENaC) in an amiloride-sensitive and dose-dependent manner in heterologous cells. Mechanistically, S3969 increases hENaC open probability through interactions requiring the extracellular domain of the beta subunit. hENaC activation by S3969 did not require cleavage by the furin protease, indicating that nonproteolyzed channels can be opened. Function of alphabetaG37Sgamma hENaC, a channel defective in gating that leads to the salt-wasting disease pseudohypoaldosteronism type I, was rescued by S3969. Small molecule activation of hENaC may find application in alleviating human disease, including pseudohypoaldosteronism type I, hypotension, and neonatal respiratory distress syndrome, when improved Na(+) flux across epithelial membranes is clinically desirable.

Lupus-associated pancreatitis.

A number of lupus patients develop episodes of acute "idiopathic" pancreatitis, unrelated to the known causes of mechanical obstruction of the pancreatic duct or toxic-metabolic etiologies. This lupus-associated pancreatitis is rare. The estimated annual incidence was 0.4-1.1/1000 lupus patients. A literature search found detailed descriptions of this condition in 77 lupus patients. Their median age was 27, and 88% were females. Abdominal pain was the most frequent pancreatitis-related symptom (88%). In 97% the diagnosis of pancreatitis was based on laboratory evidence of elevated serum amylase or lipase. Most cases were unrelated to treatment with steroids or azathioprine. Most of the patients (84%) had active lupus at the time of pancreatitis. Mortality rate was 27%, higher than in non-SLE associated pancreatitis. Active lupus and several biochemical abnormalities, but not treatment with steroids or azathioprine, were significantly associated with increased mortality. Treatment with steroids lowered the mortality by 67% compared to non-treated patients.

Lupus-associated pancreatitis.

OBJECTIVES: Involvement of the pancreas in systemic lupus erythematosus is rare. The purpose of this article is to provide a detailed review of lupus-associated pancreatitis. METHODS: We describe 3 patients with lupus-associated pancreatitis and review the English literature of the last 30 years, including the demographic, clinical, therapeutic, and prognostic aspects of this disorder. RESULTS: There were detailed descriptions of 77 patients, 88% were females. Median age was 27 years. In 44% of the patients pancreatitis developed within 1 year of the diagnosis of lupus, and 84% had active lupus at the time of pancreatitis. Abdominal pain was the most frequent pancreatitis-related symptom (88%), followed by nausea or vomiting (67%). In 97% the diagnosis of pancreatitis was based on laboratory evidence of elevated serum amylase or lipase. Abdominal computerized tomography and ultrasonography did not show signs of pancreatic involvement in 24 and 45%, respectively. The mortality rate was 27%; active lupus and some biochemical abnormalities were significantly associated with increased mortality. Treatment with corticosteroids or azathioprine was not associated with increased mortality. On the contrary, mortality was decreased in patients who were treated with these agents after the onset of pancreatitis (20% mortality, compared with 61% among those who were not treated with steroids for their pancreatitis, P = 0.005). CONCLUSIONS: Pancreatitis should be suspected in any SLE patient with abdominal pain. Mortality rate is related to both active lupus and some biochemical markers. In most cases, the onset of pancreatitis appears unrelated to previous treatment with steroids or azathioprine. Moreover, treatment with these medications improves prognosis.

Self-starting ultralow-jitter pulse source based on coupled optoelectronic oscillators with an intracavity fiber parametric amplifier.

A self-starting optical pulse source based on mutually coupled optoelectronic oscillators is described. The system employs a phototransistor-based microwave oscillator that is coupled to a fiber cavity optoelectronic oscillator with an intracavity fiber parametric amplifier. It self-starts and exhibits 3 ps pulses at a rate of 10 GHz with extremely low jitter of 30, 29, and 40 fs (for integration bandwidths of 100 Hz-15 kHz, 500 Hz-1 MHz, and 100 Hz-1 MHz, respectively).

Tunable all optical delay via slow and fast light propagation in a Raman assisted fiber optical parametric amplifier: a route to all optical buffering.

We propose and demonstrate the use of narrow band optical parametric amplification for tunable slow and fast light propagation in optical fibers. The parametric gain is coupled to the Raman process which changes the gain value moderately but modifies the gain spectral shape. Consequently, the delay is enhanced at short wavelengths while it is moderated at long wavelengths. The maximum delay and tuning range can be optimized with respect to each other considering saturation effects in long fibers. The proposed scheme offers tunable delay in the presence of gain and with a bandwidth which is sufficiently wide to process digital data streams at tens of Gbit/s rates as well as picoseconds pulses.

A fluorophore attached to nicotinic acetylcholine receptor beta M2 detects productive binding of agonist to the alpha delta site.

To study conformational transitions at the muscle nicotinic acetylcholine (ACh) receptor (nAChR), a rhodamine fluorophore was tethered to a Cys side chain introduced at the beta 19' position in the M2 region of the nAChR expressed in Xenopus oocytes. This procedure led to only minor changes in receptor function. During agonist application, fluorescence increased by (Delta F/F) approximately 10%, and the emission peak shifted to lower wavelengths, indicating a more hydrophobic environment for the fluorophore. The dose-response relations for Delta F agreed well with those for epibatidine-induced currents, but were shifted approximately 100-fold to the left of those for ACh-induced currents. Because (i) epibatidine binds more tightly to the alpha gamma-binding site than to the alpha delta site and (ii) ACh binds with reverse-site selectivity, these data suggest that Delta F monitors an event linked to binding specifically at the alpha delta-subunit interface. In experiments with flash-applied agonists, the earliest detectable Delta F occurs within milliseconds, i.e., during activation. At low [ACh] (< or = 10 microM), a phase of Delta F occurs with the same time constant as desensitization, presumably monitoring an increased population of agonist-bound receptors. However, recovery from Delta F is complete before the slowest phase of recovery from desensitization (time constant approximately 250 s), showing that one or more desensitized states have fluorescence like that of the resting channel. That conformational transitions at the alpha delta-binding site are not tightly coupled to channel activation suggests that sequential rather than fully concerted transitions occur during receptor gating. Thus, time-resolved fluorescence changes provide a powerful probe of nAChR conformational changes.