Rapid resolution of severe subcutaneous emphysema causing respiratory failure with subcutaneous drain.

This case reports on a critically ill patient (Male, 74) with severe subcutaneous emphysema which progressed to causing respiratory distress. We document both the severity of the condition we observed and then present a novel intervention. In this case, we decompressed the patient at the intensive care unit-bedside and resolved the condition. While subcutaneous emphysema is relatively common, the severity of the condition we observed, and the lack of definitive treatment guidance have prompted us to present this case as a plausible treatment guide.

Exhaled Nitric Oxide Changes During Acclimatization to High Altitude: A Descriptive Study.

Summerfield, Douglas T., Kirsten E. Coffman, Bryan J. Taylor, Amine N. Issa, and Bruce D. Johnson. Exhaled nitric oxide changes during acclimatization to high altitude: a descriptive study. High Alt Med Biol. 19:215-220, 2018. AIMS: This study describes differences in the partial pressures of exhaled nitric oxide (PeNO) between subjects fully acclimatized (ACC) to 5300 m and those who have just arrived to high altitude. METHODS: PeNO was determined in eight subjects newly exposed and nonacclimatized (non-ACC) to high altitude and compared with that in nine subjects who had ACC to high altitude for 1 month. In addition, systolic pulmonary artery pressure (sPAP) and arterial oxygen saturation (SaO2) were measured in all participants. These measurements were repeated in the non-ACC group 5 and 9 days later. RESULTS: PeNO levels on day 1 were significantly higher in the non-ACC versus ACC cohort (8.7 ± 3.5 vs. 3.9 ± 2.2 nmHg, p = 0.004). As the non-ACC group remained at altitude, PeNO levels fell and were not different when compared with those of the ACC group by day 9 (5.9 ± 2.4 vs. 3.9 ± 2.2 nmHg, p = 0.095). Higher sPAP was correlated with lower PeNO levels in all participants (R = -0.50, p = 0.043). PeNO levels were not correlated with SaO2. CONCLUSIONS: As individuals acclimatized to high altitude, PeNO levels decreased. Even after acclimatization, PeNO levels continued to play a role in pulmonary vascular tone.

Interstitial lung fluid balance in healthy lowlanders exposed to high-altitude.

We aimed to assess lung fluid balance before and after gradual ascent to 5150m. Lung diffusion capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO) and ultrasound lung comets (ULCs) were assessed in 12 healthy lowlanders at sea-level, and on Day 1, Day 5 and Day 9 after arrival at Mount Everest Base Camp (EBC). EBC was reached following an 8-day hike at progressively increasing altitudes starting at 2860m. DLCO was unchanged from sea-level to Day 1 at EBC, but increased on Day 5 (11±10%) and Day 9 (10±9%) vs. sea-level (P≤0.047). DmCO increased from sea-level to Day 1 (9±6%), Day 5 (12±8%), and Day 9 (17±11%) (all P≤0.001) at EBC. There was no change in ULCs from sea-level to Day 1, Day 5 and Day 9 at EBC. These data provide evidence that interstitial lung fluid remains stable or may even decrease relative to at sea-level following 8days of gradual exposure to high-altitude in healthy humans.

Guidelines for the Appropriate Use of Bedside General and Cardiac Ultrasonography in the Evaluation of Critically Ill Patients-Part II: Cardiac Ultrasonography.

OBJECTIVE: To establish evidence-based guidelines for the use of bedside cardiac ultrasound, echocardiography, in the ICU and equivalent care sites. METHODS: Grading of Recommendations, Assessment, Development and Evaluation system was used to rank the "levels" of quality of evidence into high (A), moderate (B), or low (C) and to determine the "strength" of recommendations as either strong (strength class 1) or conditional/weak (strength class 2), thus generating six "grades" of recommendations (1A-1B-1C-2A-2B-2C). Grading of Recommendations, Assessment, Development and Evaluation was used for all questions with clinically relevant outcomes. RAND Appropriateness Method, incorporating the modified Delphi technique, was used in formulating recommendations related to terminology or definitions or in those based purely on expert consensus. The process was conducted by teleconference and electronic-based discussion, following clear rules for establishing consensus and agreement/disagreement. Individual panel members provided full disclosure and were judged to be free of any commercial bias. RESULTS: Forty-five statements were considered. Among these statements, six did not achieve agreement based on RAND appropriateness method rules (majority of at least 70%). Fifteen statements were approved as conditional recommendations (strength class 2). The rest (24 statements) were approved as strong recommendations (strength class 1). Each recommendation was also linked to its level of quality of evidence and the required level of echo expertise of the intensivist. Key recommendations, listed by category, included the use of cardiac ultrasonography to assess preload responsiveness in mechanically ventilated (1B) patients, left ventricular (LV) systolic (1C) and diastolic (2C) function, acute cor pulmonale (ACP) (1C), pulmonary hypertension (1B), symptomatic pulmonary embolism (PE) (1C), right ventricular (RV) infarct (1C), the efficacy of fluid resuscitation (1C) and inotropic therapy (2C), presence of RV dysfunction (2C) in septic shock, the reason for cardiac arrest to assist in cardiopulmonary resuscitation (1B-2C depending on rhythm), status in acute coronary syndromes (ACS) (1C), the presence of pericardial effusion (1C), cardiac tamponade (1B), valvular dysfunction (1C), endocarditis in native (2C) or mechanical valves (1B), great vessel disease and injury (2C), penetrating chest trauma (1C) and for use of contrast (1B-2C depending on indication). Finally, several recommendations were made regarding the use of bedside cardiac ultrasound in pediatric patients ranging from 1B for preload responsiveness to no recommendation for RV dysfunction. CONCLUSIONS: There was strong agreement among a large cohort of international experts regarding several class 1 recommendations for the use of bedside cardiac ultrasound, echocardiography, in the ICU. Evidence-based recommendations regarding the appropriate use of this technology are a step toward improving patient outcomes in relevant patients and guiding appropriate integration of ultrasound into critical care practice.

Prostate Cancer in Pilots.

BACKGROUND: Aviation exposes pilots to various occupationally related hazards, including ionizing radiation and chemical combustion. The possibility of increased prostate cancer incidence and mortality among pilots is a subject of debate. This systematic review and meta-analysis aims to summarize the supporting evidence and determine the magnitude of association. METHODS: All studies reporting prostate cancer incidence and mortality in pilots compared to the general population were included regardless of language or size. The comprehensive search included multiple databases and manual search. A random effect model was used to pool relative risks (RR) across studies. RESULTS: The final search yielded nine studies with good methodological quality. Four studies reported the incidence of prostate cancer while six reported on mortality. Pilots had a small but statistically significant increase in the risk of developing prostate cancer [RR 1.20; 95% confidence interval (CI), 1.08-1.33], but not in prostate cancer mortality (RR 1.20; 95% CI, 0.91-1.60). CONCLUSION: Pilots appear to have a very small increase in prostate cancer incidence, but not in mortality. The clinical significance of this finding is uncertain.

Pulmonary capillary reserve and exercise capacity at high altitude in healthy humans.

PURPOSE: We determined whether well-acclimatized humans have a reserve to recruit pulmonary capillaries in response to exercise at high altitude. METHODS: At sea level, lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary capillary blood volume (V c) were measured at rest before maximal oxygen consumption ([Formula: see text]) was determined in seven adults. Then, DLCO, DmCO and V c were measured pre- and post-exhaustive incremental exercise at 5150 m after ~40 days of acclimatization. RESULTS: Immediately after exercise at high altitude, there was an increase in group mean DmCO (14 ± 10%, P = 0.040) with no pre- to post-exercise change in group mean DLCO (46.9 ± 5.8 vs. 50.6 ± 9.6 ml/min/mmHg, P = 0.213) or V c (151 ± 28 vs. 158 ± 37 ml, P = 0.693). There was, however, a ~20% increase in DLCO from pre- to post-exercise at high altitude (51.2 ± 0.2 vs. 61.1 ± 0.2 ml/min/mmHg) with a concomitant increase in DmCO (123 ± 2 vs. 156 ± 4 ml/min/mmHg) and V c (157 ± 3 vs. 180 ± 8 ml) in 2 of the 7 participants. There was a significant positive relationship between the decrease in [Formula: see text] from sea level to high altitude and the change in DLCO and lung diffusing capacity for nitric oxide (DLNO) from rest to end-exercise at high altitude. CONCLUSION: These data suggest that recruitment of the pulmonary capillaries in response to exercise at high altitude is limited in most well-acclimatized humans but that any such a reserve may be associated with better exercise capacity.

Guidelines for the Appropriate Use of Bedside General and Cardiac Ultrasonography in the Evaluation of Critically Ill Patients-Part I: General Ultrasonography.

OBJECTIVE: To establish evidence-based guidelines for the use of bedside ultrasound by intensivists and specialists in the ICU and equivalent care sites for diagnostic and therapeutic purposes for organs of the chest, abdomen, pelvis, neck, and extremities. METHODS: The Grading of Recommendations, Assessment, Development and Evaluation system was used to determine the strength of recommendations as either strong or conditional/weak and to rank the "levels" of quality of evidence into high (A), moderate (B), or low (C) and thus generating six "grades" of recommendation (1A-1B-1C-2A-2B-2C). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for all questions with clinically relevant outcomes. RAND appropriateness method, incorporating modified Delphi technique, was used in steps of GRADE that required panel judgment and for those based purely on expert consensus. The process was conducted by teleconference and electronic-based discussion, following clear rules for establishing consensus and agreement/disagreement. Individual panel members provided full disclosure and were judged to be free of any commercial bias. The process was conducted independent of industry funding. RESULTS: Twenty-four statements regarding the use of ultrasound were considered-three did not achieve agreement and nine were approved as conditional recommendations (strength class 2). The remaining 12 statements were approved as strong recommendations (strength class 1). Each recommendation was also linked to its level of quality of evidence. Key strong recommendations included the use of ultrasonography for ruling-in pleural effusion and assisting its drainage, ascites drainage, ruling-in pneumothorax, central venous cannulation, particularly for internal jugular and femoral sites, and for diagnosis of deep venous thrombosis. Conditional recommendations were given to the use of ultrasound by the intensivist for diagnosis of acalculous cholecystitis, renal failure, and interstitial and parenchymal lung diseases. No recommendations were made regarding static (vs dynamic) ultrasound guidance of vascular access or the use of needle guide devices. CONCLUSIONS: There was strong agreement among a large cohort of international experts regarding several recommendations for the use of ultrasound in the ICU. Evidence-based recommendations regarding the appropriate use of this technology are a step toward improving patient outcomes in relevant patients.

The risk of prostate cancer in pilots: a meta-analysis.

BACKGROUND: Aviation exposes pilots to various occupationally related hazards, including ionizing radiation and chemical combustion. The possible increased risk of prostate cancer among pilots in comparison to the general population is a subject of debate. This systematic review and meta-analysis aimed to determine the quality of supporting evidence and magnitude of this association. METHODS: All studies pertaining to prostate cancer in pilots were retrieved from multiple databases and from a manual search. Any study that assessed the incidence of prostate cancer relative to the incidence in the general population was included regardless of language or size. A random effect model was used to pool relative risks (RR) across studies. Heterogeneity was assessed using the Q statistic and I². RESULTS: Eight studies with a low risk of bias were included in the meta-analysis. Pilots had an increased risk of developing prostate cancer compared to the general population [RR 2.0; 95% confidence interval (CI), 1.5-2.7]. The analysis was associated with substantial heterogeneity (I² = 79%). Several subgroups had significantly increased risk, such as African American pilots (RR 10.00; 95% CI, 5.04-19.86) and military pilots (RR 3.30; 95% CI, 2.03-5.39). CONCLUSION: Pilots are at least twice as likely to develop prostate cancer compared to the general population. The implications of these findings are important considering the high prevalence of prostate cancer and the large number of pilots in the workforce.

Inhaled nitric oxide as salvage therapy in massive pulmonary embolism: a case series.

Inhaled nitric oxide (INO) has been shown to preferentially lower resistance in the pulmonary vasculature. The relative selectiveness of INO in accomplishing this effect makes it an attractive drug to administer as salvage therapy in patients with acute right ventricular failure secondary to pulmonary embolism. We describe 4 cases in which INO was used as a temporizing agent to decrease right ventricular after-load following massive near-fatal pulmonary embolism. All 4 patients survived to hospital discharge.

Parameters of LRP5 from a structural and molecular perspective.

LRP5, along with LRP6 and their Drosophila homolog, Arrow, constitute a novel subclass of the LDL receptor superfamily. The arrangement of structural motifs in these receptors is different from the other members of the superfamily, and only recently have we begun to understand the functional importance of human LRP5 (and LRP6). Whole genome positional cloning studies have identified a number of mutations in LRP5 that underlie inherited human diseases/phenotypes, particularly those involving the skeleton and the eye. A number of studies have illustrated the importance of Lrp5/6/Arrow as a co-receptor with Frizzled for the Wnt proteins and their critical role in the regulation of the Wnt/beta-catenin signaling pathway. The cataloging of these human mutations, in combination with engineered mutations in mice and other studies involving gene/protein modifications, has led to a better understanding of the function of the various domains in LRP5/6. In this review, we discuss a number of studies that have revealed a wide variety of protein-protein interactions that occur with the various structural motifs in the Lrp5 protein. Ultimately, these interactions regulate the activity of the Wnt/beta-catenin signaling pathway and the role it plays in processes such as bone mass accrual and vision.

Cluster II che genes from Pseudomonas aeruginosa are required for an optimal chemotactic response.

Pseudomonas aeruginosa, a gamma-proteobacterium, is motile by means of a single polar flagellum and is chemotactic to a variety of organic compounds and phosphate. P. aeruginosa has multiple homologues of Escherichia coli chemotaxis genes that are organized into five gene clusters. Previously, it was demonstrated that genes in cluster I and cluster V are essential for chemotaxis. A third cluster (cluster II) contains a complete set of che genes, as well as two genes, mcpA and mcpB, encoding methyl-accepting chemotaxis proteins. Mutations were constructed in several of the cluster II che genes and in the mcp genes to examine their possible contributions to P. aeruginosa chemotaxis. A cheB2 mutant was partially impaired in chemotaxis in soft-agar swarm plate assays. Providing cheB2 in trans complemented this defect. Further, overexpression of CheB2 restored chemotaxis to a completely nonchemotactic, cluster I, cheB-deficient strain to near wild-type levels. An mcpA mutant was defective in chemotaxis in media that were low in magnesium. The defect could be relieved by the addition of magnesium to the swarm plate medium. An mcpB mutant was defective in chemotaxis when assayed in dilute rich soft-agar swarm medium or in minimal-medium swarm plates containing any 1 of 60 chemoattractants. The mutant phenotype could be complemented by the addition of mcpB in trans. Overexpression of either McpA or McpB in P. aeruginosa or Escherichia coli resulted in impairment of chemotaxis, and these cells had smooth-swimming phenotypes when observed under the microscope. Expression of P. aeruginosa cheA2, cheB2, or cheW2 in E. coli K-12 completely disrupted wild-type chemotaxis, while expression of cheY2 had no effect. These results indicate that che cluster II genes are expressed in P. aeruginosa and are required for an optimal chemotactic response.