Benign multinodular goitre presenting as acute decompensated type two respiratory failure.

Acute airway obstruction is a life-threatening complication of benign goitre mostly occurring in cases of known progressing goitres. The index presentation of goitre with decompensated type two respiratory failure is an exceedingly rare and a diagnostically challenging presentation. We discuss the case of a woman in her 50 s, who had been diagnosed with asthma by her general practitioner, but during admission was found to have a large goitre with retrosternal extension causing critical tracheal compression. She presented with acute decompensated type two respiratory failure. We explore the diagnostic confounding posed by the patient's background of asthma and describe the initial management of the patient with non-invasive ventilation by the emergency department. The diagnosis of upper airway obstruction was not apparent which is an interesting anomaly in this case. She underwent an emergency hemithyroidectomy and recovered with a resolution of her respiratory symptoms. Histology confirmed benign multinodular hyperplasia.

Risk factors for hypoactive delirium in patients with nontraumatic ARDS: a prospective observational study.

To investigate the incidence, characteristics and risk factors for hypoactive delirium in patients with nontraumatic acute respiratory distress syndrome (ARDS) and to explore the independent risk factors associated with hypoactive delirium and provide new ideas for early prediction and treatment. Hypoactive delirium is a known serious complication in ARDS patients, and currently, there are no effective early detection models or clinical prediction tools, and there is a lack of clinical treatment. This study included nontraumatic ARDS patients who stayed in the intensive care unit (ICU) for more than 24 h and were older than 18 years. A total of 205 ARDS patients admitted to the ICU of Gansu Provincial People's Hospital between December 2021 and February 2023 were selected. Demographic data, clinical characteristics and laboratory test results were collected within 24 h after the patients entered the ICU. Multivariate logistic regression analysis was used to investigate risk factors, evaluate the clinical prediction effect of the model and construct a nomogram for visual display. The incidence of hypoactive delirium among the patients included in the study was 41%. Patients with hypoactive delirium had hypertension; diabetes mellitus; Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ≥ 15; and increased procalcitonin, C-reactive protein (CRP), lactic dehydrogenase and interleukin-6 (IL-6) levels compared with those without hypoactive delirium. Logistic regression analysis revealed that diabetes mellitus (OR 3.305, 95% CI: 1.866-12.616; p = 0.047), CRP level (OR 1.002, 95% CI: 1.001-1.023; p = 0.044), and IL-6 level (OR 1.045, 95% CI: 1.017-1.063; p = 0.001) were independent risk factors for hypoactive delirium. After receiver operating characteristic (ROC) curve analysis, calibration plot and decision curve analysis (DCA) confirmed that the clinical prediction ability of this study model was satisfactory, and a nomogram was drawn for visual display. Hypoactive delirium is a common serious complication in nontraumatic ARDS patients. Our logistic regression model not only effectively predicts hypoactive delirium early but also reveals potential clinical therapeutic targets.

Effects of prone positioning on lung mechanical power components in patients with acute respiratory distress syndrome: a physiologic study.

BACKGROUND: Prone positioning (PP) homogenizes ventilation distribution and may limit ventilator-induced lung injury (VILI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The static and dynamic components of ventilation that may cause VILI have been aggregated in mechanical power, considered a unifying driver of VILI. PP may affect mechanical power components differently due to changes in respiratory mechanics; however, the effects of PP on lung mechanical power components are unclear. This study aimed to compare the following parameters during supine positioning (SP) and PP: lung total elastic power and its components (elastic static power and elastic dynamic power) and these variables normalized to end-expiratory lung volume (EELV). METHODS: This prospective physiologic study included 55 patients with moderate to severe ARDS. Lung total elastic power and its static and dynamic components were compared during SP and PP using an esophageal pressure-guided ventilation strategy. In SP, the esophageal pressure-guided ventilation strategy was further compared with an oxygenation-guided ventilation strategy defined as baseline SP. The primary endpoint was the effect of PP on lung total elastic power non-normalized and normalized to EELV. Secondary endpoints were the effects of PP and ventilation strategies on lung elastic static and dynamic power components non-normalized and normalized to EELV, respiratory mechanics, gas exchange, and hemodynamic parameters. RESULTS: Lung total elastic power (median [interquartile range]) was lower during PP compared with SP (6.7 [4.9-10.6] versus 11.0 [6.6-14.8] J/min; P < 0.001) non-normalized and normalized to EELV (3.2 [2.1-5.0] versus 5.3 [3.3-7.5] J/min/L; P < 0.001). Comparing PP with SP, transpulmonary pressures and EELV did not significantly differ despite lower positive end-expiratory pressure and plateau airway pressure, thereby reducing non-normalized and normalized lung elastic static power in PP. PP improved gas exchange, cardiac output, and increased oxygen delivery compared with SP. CONCLUSIONS: In patients with moderate to severe ARDS, PP reduced lung total elastic and elastic static power compared with SP regardless of EELV normalization because comparable transpulmonary pressures and EELV were achieved at lower airway pressures. This resulted in improved gas exchange, hemodynamics, and oxygen delivery. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://drks.de/search/en/trial/DRKS00017449.

The Effect of Positive Pressure Ventilation on Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome: An Observational Study.

INTRODUCTION: Acute kidney injury (AKI) is frequent in critically ill COVID-19 patients and is associated with a higher mortality risk. By increasing intrathoracic pressure, positive pressure ventilation (PPV) may reduce renal perfusion pressure by reducing venous return to the heart or by increasing renal venous congestion. This study's aim was to evaluate the association between AKI and haemodynamic and ventilatory parameters in COVID-19 patients with ARDS. METHODS: This is a single-centre retrospective observational study. Consecutive patients diagnosed with COVID-19 who met ARDS criteria and required invasive mechanical ventilation were enrolled. The relationship between respiratory and haemodynamic parameters influenced by PPV and AKI development was evaluated. AKI was defined according to KDIGO criteria. AKI recovery was evaluated a month after ICU admission and patients were classified as "recovered," if serum creatinine (sCr) value returned to baseline, or as having "acute kidney disease" (AKD), if criteria for AKI stage 1 or greater persisted. The 6-month all-cause mortality was collected. RESULTS: A total of 144 patients were included in the analysis. AKI occurred in 69 (48%) patients and 26 (18%) required renal replacement therapy. In a multivariate logistic regression analysis, sex, hypertension, cumulative dose of furosemide, fluid balance, and plateau pressure were independently associated with AKI. Mortality at 6 months was 50% in the AKI group and 32% in the non-AKI group (p = 0.03). Among 36 patients who developed AKI and were discharged alive from the hospital, 56% had a full renal recovery after a month, while 14%, 6%, and 14% were classified as having an AKD of stage 0, 2, and 3, respectively. CONCLUSIONS: In our cohort, AKI was independently associated with multiple variables, including high plateau pressure, suggesting a possible role of PPV on AKI development. Further studies are needed to clarify the role of mechanical ventilation on renal function.

Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia.

RATIONALE: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

The occurrence of pressure injuries and related risk factors in patients undergoing extracorporeal membrane oxygenation for respiratory failure: A retrospective single centre study.

INTRODUCTION: Limited data is available regarding the incidence of pressure injuries in patients who have undergone Extracorporeal Membrane Oxygenation (ECMO), a life-saving technique that provides respiratory support for hypoxemia that does not respond to conventional treatment. AIM: To assess the incidence of pressure injuries and identify the risk factors in Acute Respiratory Distress Syndrome patients receiving ECMO. METHODS: A retrospective observational study utilizing prospectively collected data was performed in an Italian intensive care unit, between 1 January 2012 and 30 April 2022 enrolling all consecutive patients with Acute Respiratory Distress Syndrome who underwent ECMO. RESULTS: One hundred patients were included in this study. 67 patients (67%) developed pressure injuries during their intensive care unit stay, with a median of 2 (1-3) sites affected. The subgroup of patients with pressure injuries was more hypoxic before ECMO implementation, received more frequent continuous renal replacement therapy and prone positioning, and showed prolonged ECMO duration, intensive care unit and hospital length of stay compared to patients without pressure injuries. The logistic model demonstrated an independent association between the pO2/FiO2 ratio prior to ECMO initiation, the utilization of the prone positioning during ECMO, and the occurrence of pressure injuries. CONCLUSIONS: The incidence of pressure injuries was elevated in patients with Adult Respiratory Distress Syndrome who received ECMO. The development of pressure injuries was found to be independently associated with hypoxemia before ECMO initiation and the utilization of prone positioning during ECMO. IMPLICATIONS FOR CLINICAL PRACTICE: Patients who require ECMO for respiratory failure are at a high risk of developing pressure injuries. To ensure optimal outcomes during ECMO implementation and treatment, it is vital to implement preventive measures and to closely monitor skin health in at-risk areas.

Macklin Effect: From Pathophysiology to Clinical Implication.

Air leak syndromes (such as pneumomediastinum, pneumothorax, or subcutaneous emphysema) are frequent complications of acute respiratory distress syndrome (ARDS). Unfortunately, the development of air leaks is associated with worse outcomes. In addition, it has been hypothesized that the development of pneumomediastinum could be a marker of disease severity in patients with respiratory failure receiving noninvasive respiratory support or assisted ventilation. The so-called Macklin effect (or pulmonary interstitial emphysema) is the air dissection of the lung bronchovascular tree from peripheral to central airways following injury to distal alveoli. Ultimately, the progression of the Macklin effect leads to the development of pneumomediastinum, subcutaneous emphysema, or pneumothorax. The Macklin effect is identifiable on a chest computed tomography (CT) scan. The Macklin effect could be an accurate predictor of barotrauma in patients with ARDS (sensitivity = 89.2% [95% CI: 74.6-96.9]; specificity = 95.6% [95% CI: 90.6-98.4]), and may be a marker of disease severity. Accordingly, the detection of the Macklin effect on a chest CT scan could be used to select which patients with ARDS might benefit from different treatment algorithms, including advanced respiratory monitoring, early intubation, or, potentially, the institution of early extracorporeal support with or without invasive ventilation. In this video, the authors summarize the pathophysiology and potential clinical significance and applications of the Macklin effect in patients with acute respiratory failure.

Presepsin is a more useful predictor of septic AKI and ARDS for very-old sepsis patients than for young sepsis patients in ICUs: a pilot study.

OBJECTIVE: Sepsis is a syndrome of life-threatening organ dysfunction. This study aimed to determine whether presepsin is a useful predictor of septic acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and shock in very-old sepsis patients aged 75 years in intensive care units (ICUs). RESULTS: A total of 83 adult patients diagnosed with sepsis were prospectively examined and divided into two groups: those aged 75 years and older (over 75 group) and those aged younger than 75 years (under 75 group). Presepsin values were measured after ICU admission. Inflammation-based prognostic scores were also examined. For category classification, total scores ("inflammation-presepsin scores [iPS]") were calculated. Presepsin values, inflammation-based prognostic scores, and iPS were compared between patients with septic AKI, ARDS, DIC, or shock and those without these disorders in the over 75 and under 75 groups. Areas under the curve of presepsin for predicting septic AKI and ARDS in the over 75 group were both > 0.7, which were significantly higher than those in the under 75 group. In conclusion, presepsin is a more useful predictor of septic AKI and ARDS for very-old sepsis patients (over 75 years) than for younger sepsis patients (under 75 years).

Host and Microbe Blood Metagenomics Reveals Key Pathways Characterizing Critical Illness Phenotypes.

Rationale: Two molecular phenotypes of sepsis and acute respiratory distress syndrome, termed hyperinflammatory and hypoinflammatory, have been consistently identified by latent class analysis in numerous cohorts, with widely divergent clinical outcomes and differential responses to some treatments; however, the key biological differences between these phenotypes remain poorly understood.Objectives: We used host and microbe metagenomic sequencing data from blood to deepen our understanding of biological differences between latent class analysis-derived phenotypes and to assess concordance between the latent class analysis-derived phenotypes and phenotypes reported by other investigative groups (e.g., Sepsis Response Signature [SRS1-2], molecular diagnosis and risk stratification of sepsis [MARS1-4], reactive and uninflamed).Methods: We analyzed data from 113 patients with hypoinflammatory sepsis and 76 patients with hyperinflammatory sepsis enrolled in a two-hospital prospective cohort study. Molecular phenotypes had been previously assigned using latent class analysis.Measurements and Main Results: The hyperinflammatory and hypoinflammatory phenotypes of sepsis had distinct gene expression signatures, with 5,755 genes (31%) differentially expressed. The hyperinflammatory phenotype was associated with elevated expression of innate immune response genes, whereas the hypoinflammatory phenotype was associated with elevated expression of adaptive immune response genes and, notably, T cell response genes. Plasma metagenomic analysis identified differences in prevalence of bacteremia, bacterial DNA abundance, and composition between the phenotypes, with an increased presence and abundance of Enterobacteriaceae in the hyperinflammatory phenotype. Significant overlap was observed between these phenotypes and previously identified transcriptional subtypes of acute respiratory distress syndrome (reactive and uninflamed) and sepsis (SRS1-2). Analysis of data from the VANISH trial indicated that corticosteroids might have a detrimental effect in patients with the hypoinflammatory phenotype.Conclusions: The hyperinflammatory and hypoinflammatory phenotypes have distinct transcriptional and metagenomic features that could be leveraged for precision treatment strategies.

Degree of COVID-19 severity and mortality in stroke: correlation of clinical and laboratory parameters.

BACKGROUND: Stroke is one of the neurological manifestations of COVID-19, leading to a significant risk of morbidity and mortality. Clinical manifestations and laboratory parameters were investigated to determine mortality predictors in this case. METHOD: The case control study was conducted at Dr. Sardjito General Hospital,Yogyakarta, Indonesia, with data collected between July 2020 and August 2021. All recorded clinical and laboratory data from acute stroke patients with confirmed COVID-19 were collected. Baseline characteristics, bivariate, and multivariate analyses were assessed to determine significant predictors for mortality. RESULT: This study involved 72 subjects with COVID-19 and stroke. The majority experienced ischemic stroke, with hypertension as the most prevalent comorbidity. Notably, 45.8% of subjects (p < 0.05) loss of consciousness and 72.2% of exhibited motor deficits (p < 0.05). Severe degree of COVID-19 was observed in 52.8% of patients, with respiratory distress and death rates of 56.9% and 58.3%. Comparison of surviving and deceased groups highlighted significant differences in various clinical and laboratory characteristics differences. Hazard ratio (HR) analysis identified loss of consciousness (HR = 2.68; p = 0.01), motor deficit (HR = 2.34; p = 0.03), respiratory distress (HR = 81.51; p < 0.001), and monocyte count (HR:1.002; p = 0.04) as significant predictors of mortality. CONCLUSION: Mortality in COVID-19 patients with stroke was significantly associated with loss of consciousness, motor deficit, respiratory distress, and raised monocyte count. The risk of mortality is heightened when multiple factors coexist.

Atrial flutter complicating acute respiratory distress syndrome (ARDS): A rare case report.

RATIONALE: This case report addresses a unique instance of atrial flutter complicating acute respiratory distress syndrome (ARDS), contributing a novel addition to the medical literature. The co-occurrence of these conditions sheds light on a rare clinical scenario that requires careful consideration. PATIENT CONCERNS: The patient exhibited symptoms of pronounced dyspnea, tachypnea, and hypoxemia. Clinical assessment revealed irregular heart rhythms, notably atrial flutter, alongside characteristic signs of ARDS, including bilateral pulmonary infiltrates and reduced lung compliance. DIAGNOSES AND INTERVENTIONS: After a comprehensive evaluation, the patient was diagnosed with atrial flutter complicating ARDS. Therapeutic measures encompassed antiarrhythmic agents, mechanical ventilation, and targeted ARDS management protocols. The intricate interplay between cardiac and respiratory factors necessitated a multidisciplinary approach. OUTCOMES: Throughout treatment, the patient's respiratory distress gradually improved. Control of the atrial flutter was achieved, and oxygenation levels were restored within acceptable limits. This successful outcome underscores the significance of a well-coordinated treatment strategy in addressing complex cases like this. LESSONS: This case highlights the importance of recognizing and managing the intricate relationship between cardiac arrhythmias such as atrial flutter and respiratory complications like ARDS. The successful management of this patient underscores the value of multidisciplinary collaboration and tailored therapeutic interventions. Practitioners should remain vigilant for such rare complications and consider this case a reminder of the potential complexities that can arise in critical care scenarios.

Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.

Cell-free hemoglobin triggers macrophage cytokine production via TLR4 and MyD88.

Cell-free hemoglobin (CFH) is elevated in the airspace of patients with acute respiratory distress syndrome (ARDS) and is sufficient to cause acute lung injury in a murine model. However, the pathways through which CFH causes lung injury are not well understood. Toll-like receptor 4 (TLR4) is a mediator of inflammation after detection of damage- and pathogen-associated molecular patterns. We hypothesized that TLR4 signaling mediates the proinflammatory effects of CFH in the airspace. After intratracheal CFH, BALBc mice deficient in TLR4 had reduced inflammatory cell influx into the airspace [bronchoalveolar lavage (BAL) cell counts, median TLR4 knockout (KO): 0.8 × 104/mL [IQR 0.4-1.2 × 104/mL], wild-type (WT): 3.0 × 104/mL [2.2-4.0 × 104/mL], P < 0.001] and attenuated lung permeability (BAL protein, TLR4KO: 289 µg/mL [236-320], WT: 488 µg/mL [422-536], P < 0.001). These mice also had attenuated production of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the airspace. C57Bl/6 mice lacking TLR4 on myeloid cells only (LysM.Cre+/-TLR4fl/fl) had reduced cytokine production in the airspace after CFH, without attenuation of lung permeability. In vitro studies confirm that WT primary murine alveolar macrophages exposed to CFH (0.01-1 mg/mL) had dose-dependent increases in IL-6, IL-1 ß, CXC motif chemokine ligand 1 (CXCL-1), TNF-α, and IL-10 (P < 0.001). Murine MH-S alveolar-like macrophages show TLR4-dependent expression of IL-1ß, IL-6, and CXCL-1 in response to CFH. Primary alveolar macrophages from mice lacking TLR4 adaptor proteins myeloid differentiation primary response 88 (MyD88) or TIR-domain-containing adapter-inducing interferon-ß (TRIF) revealed that MyD88KO macrophages had 71-96% reduction in CFH-dependent proinflammatory cytokine production (P < 0.001), whereas macrophages from TRIFKO mice had variable changes in cytokine responses. These data demonstrate that myeloid TLR4 signaling through MyD88 is a key regulator of airspace inflammation in response to CFH.NEW & NOTEWORTHY Cell-free hemoglobin (CFH) is elevated in the airspace of most patients with acute respiratory distress syndrome and causes severe inflammation. Here, we identify that CFH contributes to macrophage-induced cytokine production via Toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) signaling. These data increase our knowledge of the mechanisms through which CFH contributes to lung injury and may inform development of targeted therapeutics to attenuate inflammation.

Outcomes in Obese Adult Veno-Venous Extracorporeal Membrane Oxygenation: A Systematic Review.

Obesity is associated with an overall increased risk of morbidity and mortality. However, in patients with critical illness, sepsis, and acute respiratory distress syndrome, obesity may be protective, termed "the obesity paradox." This is a systematic literature review of articles published from 2000 to 2022 evaluating complications and mortality in adults with respiratory failure on veno-venous extracorporeal membrane oxygenation (VV ECMO) based on body mass index (BMI). Eighteen studies with 517 patients were included. Common complications included acute renal failure (175/377, 46.4%), venous thrombosis (175/293, 59.7%), and bleeding (28/293, 9.6%). Of the six cohort studies, two showed improved mortality among obese patients, two showed a trend toward improved mortality, and two showed no difference. Comparing all patients in the studies with BMI of less than 30 to those with BMI of greater than or equal to 30, we noted decreased mortality with obesity (92, 37.1% of BMI <30 vs. 30, 11% of BMI ≥30, p ≤ 0.0001). Obesity may be protective against mortality in adult patients undergoing VV ECMO. Morbid and super morbid obesity should not be considered a contraindication to cannulation, with patients with BMI ≥ 80 surviving to discharge. Complications may be high, however, with higher rates of continuous renal replacement therapy and thrombosis among obese patients.

Respiratory Distress Caused by Neoplastic Upper Respiratory Tract Obstructions in 2 Pet Rats (Rattus norvegicus domestica).

Respiratory disease is one of the primary reasons for pet owners to seek veterinary attention for their rats. While chronic respiratory disease complex is most often responsible for respiratory signs in pet rats and is well characterized, upper respiratory obstructive disease has been rarely reported in the literature. This report describes 2 pet fancy rats (Rattus norvegicus domestica) presenting with a several day history of progressive respiratory signs that were minimally responsive to supportive therapies, including antibiotics, nonsteroidal anti-inflammatories, and fluid and oxygen support. Survey radiographs were performed under sedation in both cases. In the first case, no cause for the clinical signs could be identified, in part due to suboptimal radiographic positioning, although severe aerophagia was noted. In the second case, cervical tracheal luminal narrowing and increased soft tissue opacity along the walls of the trachea were identified. Both rats declined while under sedation, resulting in cardiopulmonary arrest in the first case and humane euthanasia in the second. On necropsy, the first case had a oropharyngeal squamous cell carcinoma originating from the Zymbal's gland, which was obstructing the larynx. The second case had an intra-luminal tracheal mass obstructing the airway. This was mostly likely B-cell lymphoma or a plasma cell tumor, although definitive diagnosis was unable to be obtained. For future such cases empiric management of respiratory disease in rats with antimicrobials, anti-inflammatories, and supportive care is often appropriate based on the high prevalence of infectious agents, however, other noninfectious causes should be considered, such as neoplastic processes leading to upper airway obstructive disease and diagnostic imaging may be indicated.

Acute respiratory failure developing in a patient with lymphomatoid granulomatosis.

Lymphomatoid granulomatosis (LYG) is a rare B cell lymphoproliferative disorder associated with Epstein-Barr virus infection. LYG diagnosis is often difficult because of non-specific and varied radiological and pathological findings. The lung is the most common organ of LYG occurrence, but extrapulmonary lesions involving the central nervous system, skin, kidneys and liver are observed. A surgical biopsy is often inevitable for LYG diagnosis.We encountered a man in his 50s who presented with progressive dyspnoea. Extrapulmonary lesions were not observed. Although he developed respiratory failure within a short period, a low dose of corticosteroid relieved his symptoms. Video-assisted thoracoscopic lung biopsy revealed grade 1 LYG. The patient was successfully treated with chemotherapy, including rituximab. Only a few cases of LYG with progressive respiratory failure are reported, and most have been diagnosed via autopsy. Our case highlights the importance of performing a surgical lung biopsy at the appropriate time to diagnose LYG.

From pressure to tension: a model of damaging inflation stress.

Although the stretch that generates ventilator-induced lung injury (VILI) occurs within the peripheral tissue that encloses the alveolar space, airway pressures and volumes monitor the gas within the interior core of the lung unit, not its cellular enclosure. Measured pressures (plateau pressure, positive end-expiratory pressure, and driving pressure) and tidal volumes paint a highly relevant but incomplete picture of forces that act on the lung tissues themselves. Convenient and clinically useful measures of the airspace, such as pressure and volume, neglect the partitioning of tidal elastic energy into the increments of tension and surface area that constitute actual stress and strain at the alveolar margins. More sharply focused determinants of VILI require estimates of absolute alveolar dimension and morphology and the lung's unstressed volume at rest. We present a highly simplified but informative mathematical model that translates the radial energy of pressure and volume of the airspace into its surface energy components. In doing so it elaborates conceptual relationships that highlight the forces tending to cause end-tidal hyperinflation of aerated units within the 'baby lung' of acute respiratory distress syndrome (ARDS).

Evaluation of feasibility phase of adaptive version of locally made bubble continuous positive airway pressure oxygen therapy for the treatment of COVID-19 positive and negative adults with severe pneumonia and hypoxaemia.

Background: Bubble continuous positive airway pressure (bCPAP) oxygen therapy has been shown to be safe and effective in treating children with severe pneumonia and hypoxaemia in Bangladesh. Due to lack of adequate non-invasive ventilatory support during coronavirus disease 2019 (COVID-19) crisis, we aimed to evaluate whether bCPAP was safe and feasible when adapted for use in adults with similar indications. Methods: Adults (18-64 years) with severe pneumonia and moderate hypoxaemia (80 to <90% oxygen saturation (SpO2) in room air) were provided bCPAP via nasal cannula at a flow rate of 10 litres per minute (l/min) oxygen at 10 centimetres (cm) H2O pressure, in two tertiary hospitals in Dhaka, Bangladesh. Qualitative interviews and focus group discussions, using a descriptive phenomenological approach, were performed with patients and staff (n = 39) prior to and after the introduction (n = 12 and n = 27 respectively) to understand the operational challenges to the introduction of bCPAP. Results: We enrolled 30 adults (median age 52, interquartile range (IQR) 40-60 years) with severe pneumonia and hypoxaemia and/or acute respiratory distress syndrome (ARDS) irrespective of coronavirus disease 2019 (COVID-19) test results to receive bCPAP. At baseline mean SpO2 on room air was 87% (±2) which increased to 98% (±2), after initiation of bCPAP. The mean duration of bCPAP oxygen therapy was 14.4 ± 24.8 hours. There were no adverse events of note, and no treatment failure or deaths. Operational challenges to the clinical introduction of bCPAP were lack of functioning pulse oximeters, difficult nasal interface fixation among those wearing nose pin, occasional auto bubbling or lack of bubbling in water-filled plastic bottle, lack of holder for water-filled plastic bottle, rapid turnover of trained clinicians at the hospitals, and limited routine care of patients by hospital clinicians particularly after official hours. Discussion: If the tertiary hospitals in Bangladesh are supplied with well-functioning good quality pulse oximeters and enhanced training of the doctors and nurses on proper use of adapted version of bCPAP, in treating adults with severe pneumonia and hypoxaemia with or without ARDS, the bCPAP was found to be safe, well tolerated and not associated with treatment failure across all study participants. These observations increase the confidence level of the investigators to consider a future efficacy trial of adaptive bCPAP oxygen therapy compared to WHO standard low flow oxygen therapy in such patients. Conclusion: s Although bCPAP oxygen therapy was found to be safe and feasible in this pilot study, several challenges were identified that need to be taken into account when planning a definitive clinical trial.