Acute Hypoxic Respiratory Failure Research Articles

Rapid Life-Saving Response to Anti-PD-1 in a Solid Organ Transplant Recipient With Metastatic Cutaneous Squamous Cell Carcinoma: A Case Report and Review.

Anti-programmed cell death protein 1 (PD-1) therapy is considered effective in the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma but the use of these agents in solid organ transplant recipients (SOTRs) is often taken with caution. While anti-tumor effects without graft rejection have been reported, studies have shown high rates of fatal graft rejection with immune checkpoint therapy. In this case report, we present an SOTR patient with life-threatening, acute hypoxic respiratory failure due to rapidly progressive metastatic cutaneous squamous cell carcinoma with lung and pleural involvement. Modification of their immunosuppressive regimen and treatment with front-line anti-PD-1 inhibitor, pembrolizumab, led to rapid clinical response with near complete resolution of metastatic pulmonary disease and no long-term evidence of graft rejection. Our case report shows that front-line treatment with PD-1 inhibitors can be safely administered in SOTR patients with rapid metastatic disease control.

RIPK1 inhibitor ameliorates pulmonary injury by modulating the function of neutrophils and vascular endothelial cells

Acute lung injury (ALI) is an acute and progressive hypoxic respiratory failure that could progress to acute respiratory distress syndrome (ARDS) with a high mortality rate, thus immediate medical attention and supportive care are necessary. The pathophysiology of ALI is characterized by the disruption of the alveolar-capillary barrier and activation of neutrophils, leading to lung tissue damage. The receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising target for the treatment of multiple inflammatory diseases, but the role of RIPK1 in the ALI remains poorly understood. In this study, we aimed to figure out the pathological role of RIPK1 in ALI, especially in the pulmonary immune microenvironment involving neutrophils and endothelial cells. In vivo experiments showed that RIPK1 inhibitor protected against lipopolysaccharide (LPS)-induced lung injury in mouse models, with reduced neutrophils and monocytes infiltration in the lungs. Further studies demonstrated that, besides the inhibitory action on necroptosis, RIPK1 inhibitor directly suppressed reactive oxygen species (ROS) generation and inflammatory cytokines secretion from neutrophils. Furthermore, RIPK1 inhibition maintains the barrier function in TNF-α-primed vascular endothelial cells and prevents their activation induced by the supernatant from LPS-stimulated neutrophils. Mechanistically, the aforementioned effects of RIPK1 inhibitor are associated with the NF-κB signaling pathway, which is partially independent of necroptosis inhibition. These results provide new evidence that RIPK1 inhibitor directly regulates the function of neutrophils and endothelial cells, as well as interferes with the interactions between these two cell types, therefore contributing to a better understanding of RIPK1 in ALI and providing a potential avenue for future therapeutic interventions.

Evaluating the diagnostic and prognostic ability of ischemia modified albumin in COVID-19

BackgroundPatients with COVID-19 can rapidly deteriorate and develop acute hypoxic respiratory failure. Prominent features of the disease include severe inflammation, endotheliitis, and thrombosis. ObjectivesThe aim of the study was to evaluate the diagnostic and prognostic effectiveness of ischemia modified albumin (ΙΜΑ) in a cohort of COVID-19 patients. MethodsThis prospective observational study included adults with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction test, who were hospitalized specifically for COVID-19. The outcomes of interest were progression to severe acute respiratory failure during the index hospitalization defined as partial pressure of oxygen/fraction of inspired oxygen lower or equal to 150, admission to the intensive care unit (ICU) and in-hospital mortality. Admission IMA levels were determined using the commercially available “IMA Assay Kit” method (Abbexa LTD, Cambridge, UK). Adults without SARS-CoV-2 infection were used as controls. Results135 COVID-19 patients and 64 controls were included. Admission IMA levels were significantly higher in COVID-19 patients compared to controls [[24.38 (11.94) ng/ml vs. 14.69 (3.52) ng/ml, p < 0.01]. Receiver operating characteristic analysis of admission IMA showed an area under the curve (AUC) of 94% (p < 0.0001) for COVID-19 diagnosis (cut-off value: 17.5 ng/ml; sensitivity: 90.37%; specificity: 87.5%). Admission IMA was also associated with mortality (AUC: 68%, p = 0.01). However, it was not associated with severe acute respiratory failure (AUC: 47%, p = 0.53) or ICU admission (AUC: 58%, p = 0.41). ConclusionAdmission IMA was significantly increased in COVID-19 patients and was associated with in-hospital mortality.

Risk factors for intubation and mortality in patients treated with high flow nasal cannula due to COVID-19 infection. Survival Analysis Study in a Northern Mexican Population.

COVID-19-related acute hypoxic respiratory failure patients often use high-flow nasal cannula (HFNO) oxygen therapy. COVID-19 HFNO intubation and mortality risk factors are understudied in the Mexican population, so the aim was to study them. This retrospective study searched electronic medical records from March 2020 to June 2022 for patients with COVID-19 who required hospitalization and HFNO. Descriptive statistics, a survival curve analysis, and Cox proportional hazard models were used to determine predictor factors for intubation and mortality in patients with HFNO and COVID-19, respectively. A total of 134 patients received HFNO treatment. Ninety-one (67.9%) were men with a mean (SD) age of 54.5 (17.9) years. Common medical history included obesity (n = 89, 66.4%) with a Body Mass Index (BMI) mean (SD) of 31.8 (5.9), hypertension (n = 67, 50.0%), type 2 diabetes (n = 55, 41.0%), and dyslipidemias (n = 43, 32.1%). The variables associated with a greater risk of requiring intubation after high-flow therapy were age (HR = 1.018, 95% CI 1.003-1.034, p = 0.022) and BMI (HR = 1.071, 95% CI 1.024-1.120, p = 0.003). No variables were associated with lower risk. Increased mortality was associated with increasing age (HR = 1.151, 95% CI 1.102-1.201, p = <0.001), hypertension (HR = 4.092, 95% CI 1.369-12.236, p = 0.012), and dyslipidemia (HR = 3.954, 95% CI 1.395-11.209, p = 0.010). Patients with type 2 diabetes had a lower risk of mortality (HR = 0.235, 95% CI 0.080-0.688, p = 0.008). A higher age and BMI were associated with an increased risk of intubation in patients with HFNO and COVID-19. Hypertension and dyslipidemias were associated with a higher risk of mortality.

Early machine learning prediction of hospitalized patients at low risk of respiratory deterioration or mortality in community-acquired pneumonia: Derivation and validation of a multivariable model.

Current prognostic tools for pneumonia predominantly focus on mortality, often neglecting other crucial outcomes such as the need for advanced respiratory support. The objective of this study was to develop and validate a tool that predicts the early risk of non-occurrence of respiratory deterioration or mortality. We conducted a single-center, retrospective cohort study involving hospitalized adult patients with community-acquired pneumonia (CAP) and acute hypoxic respiratory failure from January 2009 to December 2019 (n = 4379). We employed the gradient boosting machine (GBM) learning to create a model that estimates the likelihood of patients requiring advanced respiratory support (high flow nasal cannula [HFNC], non-invasive mechanical ventilation [NIMV], and invasive mechanical ventilation [IMV]) or facing mortality during hospitalization. This model utilized readily available data including demographic, physiologic, and laboratory data, sourced from electronic health records and obtained within the first six hours of admission. Out of the cohort, 890 patients (25.2%) either required advanced respiratory support or died during their hospital stay. Our predictive model displayed superior discrimination and higher sensitivity (cross-validation C-statistic = 0.71; specificity = 0.56; sensitivity = 0.72) compared to the pneumonia severity index (PSI) (C-statistic = 0.65; specificity = 0.91; sensitivity = 0.24; P value < 0.001), while maintaining a negative predictive value (NPV) of approximately 0.85. These data demonstrate that our machine learning model predicted the non-occurrence of respiratory deterioration or mortality among hospitalized CAP patients more accurately than the PSI. The enhanced sensitivity of this model holds potential for reliably excluding low-risk patients from pneumonia clinical trials.

March 2024 Medical Image of the Month: Sputum Cytology in Patients with Suspected Lung Malignancy Presenting with Acute Hypoxic Respiratory Failure

No abstract available. Article truncated after 150 words. A 71-year-old woman presented with right-sided mass-like consolidation and pleural effusion on CT (Figure 1A), discovered incidentally after placement of a drug-eluting stent for coronary artery disease. The patient had a medical history significant for COPD, hypertension, hyperlipidemia, and coronary artery disease, status post a recent drug-eluting stent (less than 1 month ago). The patient received a presumptive diagnosis of pneumonia with parapneumonic effusion. Findings persisted despite multiple courses of empiric antibiotic therapy. She then underwent thoracentesis; pleural fluid was exudative; however, cytology was inconclusive. An FDG PET-CT (Figure 1B) revealed hypermetabolic activity in the right lower lobe with radiotracer activity up to 7.7 SUV concerning for malignancy. Diagnostic bronchoscopy was planned; however, her condition deteriorated suddenly the day before her planned procedure. EMS found the patient to be severely hypoxic, SpO2 in the 70s. Patient was taken by ambulance to the local emergency room. Upon arrival, the patient was …

Right ventricular performance during acute hypoxic exercise.

Acute hypoxia increases pulmonary arterial (PA) pressures, though its effect on right ventricular (RV) function is controversial. The objective of this study was to characterize exertional RV performance during acute hypoxia. Ten healthy participants (34±10 years, 7males) completed three visits: visits 1 and 2 included non-invasive normoxic (fraction of inspired oxygen ( )=0.21) and isobaric hypoxic ( =0.12) cardiopulmonary exercise testing (CPET) to determine normoxic/hypoxic maximal oxygen uptake ( ). Visit 3 involved invasive haemodynamic assessments where participants were randomized 1:1 to either Swan-Ganz or conductance catheterization to quantify RV performance via pressure-volume analysis. Arterial oxygen saturation was determined by blood gas analysis from radial arterial catheterization. During visit 3, participants completed invasive submaximal CPET testing at 50% normoxic and again at 50% hypoxic ( =0.12). Median (interquartile range) values for non-invasive values during normoxic and hypoxic testing were 2.98 (2.43, 3.66) l/min and 1.84 (1.62, 2.25) l/min, respectively (P<0.0001). Mean PA pressure increased significantly when transitioning from rest to submaximal exercise during normoxic and hypoxic conditions (P=0.0014). Metrics of RV contractility including preload recruitable stroke work, dP/dtmax , and end-systolic pressure increased significantly during the transition from rest to exercise under normoxic and hypoxic conditions. Ventricular-arterial coupling was maintained during normoxic exercise at 50% . During submaximal exercise at 50% of hypoxic , ventricular-arterial coupling declined but remained within normal limits. In conclusion, resting and exertional RV functions are preserved in response to acute exposure to hypoxia at an =0.12 and the associated increase in PA pressures. KEY POINTS: The healthy right ventricle augments contractility, lusitropy and energetics during periods of increased metabolic demand (e.g. exercise) in acute hypoxic conditions. During submaximal exercise, ventricular-arterial coupling decreases but remains within normal limits, ensuring that cardiac output and systemic perfusion are maintained. These data describe right ventricular physiological responses during submaximal exercise under conditions of acute hypoxia, such as occurs during exposure to high altitude and/or acute hypoxic respiratory failure.

Covid-19 Pneumonia Presenting as a ‘Typical Radiological Bronchopneumonia’ Pattern in Clinical-Radiological-Pathological Phenotype with Transient Hyperglycemia

Radiological phenotypes are radiological patterns or observable characteristics of COVID19 pneumonia. Various phenotypic classifications have been reported in literature. CT severity radiological phenotypes are widely used and universally accepted radiological phenotypic methods. Radiological CT severity phenotypic differentiation has documented very crucial role in initial assessment and during triaging of these cases in indoor and outdoor setting. Typical COVID-19 lung parenchymal involvement described as predominant ground glass opacities (GGOs) and consolidations in peripheral and subpleural portion of any lobe, predominantly involving lower lobes. Atypical Radiological patterns in COVID-19 has been documented as bronchopneumonia, multifocal consolidations, necrotizing pneumonia, cavitations with GGOs with or without consolidations. In present case report, 43-year male, presented with acute febrile respiratory illness with acute hypoxic respiratory failure documented as oxygen saturation of 80% at room air with tachypnea and respiratory distress. HRCT thorax was showing Pleural based, peripheral, central, multifocal patchy, confluent &amp; ill-defined GGOs and consolidations in bilateral lung fields in upper, middle and lower lobes. These typical radiological features suggestive of bronchopneumonia like radiological pattern which was very unusual for typical COVID-19 radiology. His laboratory parameters have shown abnormally raised inflammatory markers like CRP, Ferritin, LDH, D-Dimer and IL-6. Importantly, his random blood sugars were raised with abnormally raised HbA1c levels to label as diabetes mellitus. He was diagnosed with diabetes mellitus this time with COVID-19 illness without use of steroids. He was treated with standardized COVID-19 management institutional protocol with combination of low molecular weight heparin, methylprednisolone, remdesivir, meropenem and teicoplanin. Patient required BIPAP support with higher oxygen requirement with nasals canula for one week due to advanced radiological disease with more anatomical involvement. We have documented successful treatment outcome with use of rational treatment in timely by predicting disease severity with use of composite analysis of clinical, laboratory and radiological markers of illness. Transient hyperglycemia is known to occur and reported after COVID-19 illness due to virus induced inflammatory response and pancreatopathy with beta cell dysfunction. Transient hyperglycemia can be easily managed with insulin during hospitalization and oral anti-diabetic agents after discharge for few weeks. Dietary and lifestyle modification will help in majority with complete reversal of abnormally high sugar levels with restoration of normal HbA1c levels to non-diabetic range.

Prevalence of Alcohol Use Characterized by Phosphatidylethanol in Patients With Respiratory Failure Before and During the COVID-19 Pandemic

BackgroundAlcohol misuse is frequently overlooked in hospitalized patients, but common among patients with pneumonia and acute hypoxic respiratory failure. Investigations in hospitalized patients heavily rely on self-report surveys or chart abstraction, which lack sensitivity. Therefore, our understanding of the prevalence of alcohol misuse before and during the COVID-19 pandemic is limited. Research QuestionIn critically ill patients with respiratory failure, did the proportion of patients with alcohol misuse, defined by the direct biomarker phosphatidylethanol (PEth), vary over a time period including the COVID-19 pandemic? Study Design and MethodsPatients with acute hypoxic respiratory failure on mechanical ventilation were enrolled prospectively during 2015-2019 (pre-pandemic) and 2020-2022 (pandemic). Alcohol use data, including alcohol use disorders identification test (AUDIT)-C scores, were collected from electronic health records, and PEth was assessed at ICU admission. The relationship between clinical variables and PEth were examined using multivariable ordinal regression. Dichotomized PEth values (≥25 ng/mL) defining alcohol misuse were compared to AUDIT-C scores signifying misuse before and during the pandemic, and correlations between log-transformed PEth and AUDIT-C scores were evaluated and compared by era. Multiple imputation by chained equations was employed to handle missing PEth data. ResultsCompared to pre-pandemic patients (n=144), patients in the pandemic cohort (n=92) included a substantially higher proportion with PEth-defined alcohol misuse (38% versus 90%, p<0.001). In adjusted models, absence of diabetes, COVID-19 positivity, and enrollment during the pandemic were each associated with higher PEth values. The correlation between healthcare worker-recorded AUDIT-C and PEth was significantly lower during the pandemic. InterpretationThe higher prevalence of PEth-defined alcohol misuse during the pandemic suggests that alcohol consumption increased during this time period, identifying alcohol misuse as a potential risk factor for severe COVID-19-associated respiratory failure. Results also suggest that AUDIT-C may be less useful in characterizing alcohol consumption during high clinical capacity.

Comparison of limited driving pressure ventilation and low tidal volume strategies in adults with acute respiratory failure on mechanical ventilation: a randomized controlled trial.

Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear. This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure. A single-centre, prospective, open-labelled, randomized controlled trial. This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH2O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment. From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00-2.67) and 1.75 (1.25-2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74-1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55-1.22, p = 0.348. In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable. The study was registered with the ClinicalTrials.gov database (identification number NCT04035915).

Effect of high flow nasal oxygen on inspiratory effort of patients with acute hypoxic respiratory failure and do not intubate orders.

High flow nasal oxygen (HFNO) is recommended as a first-line respiratory support during acute hypoxic respiratory failure (AHRF) and represents a proportionate treatment option for patients with do not intubate (DNI) orders. The aim of the study is to assess the effect of HFNO on inspiratory effort as assessed by esophageal manometry in a population of DNI patients suffering from AHRF. Patients with AHRF and DNI orders admitted to Respiratory intermediate Care Unit between January 1st, 2018 and May 31st, 2023 to receive HFNO and subjected to esophageal manometry were enrolled. Esophageal pressure swing (ΔPes), clinical variables before and after 2h of HFNO and clinical outcome (including HFNO failure) were collected and compared as appropriate. The change in physiological and clinical parameters according to the intensity of baseline breathing effort was assessed and the correlation between baseline ΔPes values and the relative change in breathing effort and clinical variables after 2h of HFNO was explored. Eighty-two consecutive patients were enrolled according to sample size calculation. Two hours after HFNO start, patients presented significant improvement in ΔPes (12 VS 16 cmH2O, p < 0.0001), respiratory rate (RR) (22 VS 28bpm, p < 0.0001), PaO2/FiO2 (133 VS 126mmHg, p < 0.0001), Heart rate, Acidosis, Consciousness, Oxygenation and respiratory rate (HACOR) score, (4 VS 6, p < 0.0001), Respiratory rate Oxygenation (ROX) index (8.5 VS 6.1, p < 0.0001) and BORG (1 VS 4, p < 000.1). Patients with baseline ΔPes below 20 cmH2O where those who improved all the explored variables, while patients with baseline ΔPes above 30 cmH2O did not report significant changes in physiological or clinical features. A significant correlation was found between baseline ΔPes values and after 2h of HFNO (R2 = 0.9, p < 0.0001). ΔPes change 2h after HFNO significantly correlated with change in BORG (p < 0.0001), ROX index (p < 0.0001), HACOR score (p < 0.001) and RR (p < 0.001). In DNI patients with AHRF, HFNO was effective in reducing breathing effort and improving respiratory and clinical variables only for those patients with not excessive inspiratory effort.

Therapeutic targeting of hypoxia inducible factor in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by bilateral chest infiltration and acute hypoxic respiratory failure. ARDS carries significant morbidity and mortality despite advancements in medical management, calling for the development of novel therapeutic targets. Hypoxia-inducible factor (HIF) is a heterodimeric protein involved in various essential pathways, including metabolic reprogramming, immune modulation, angiogenesis and cell cycle regulation. HIF is routinely degraded in homeostasis conditions via the prolyl hydroxylase domain/von Hippel-Lindau protein pathway. However, HIF is stabilized in ARDS via various mechanisms (oxygen-dependent and independent) as an endogenous protective pathway and plays multifaceted roles in different cell populations. This review focuses on the functional role of HIF and its target genes during ARDS, as well as how HIF has evolved as a therapeutic target in current medical management.

Factors Associated with in-Hospital Mortality in Patients with Burkitt Lymphoma - Analysis of the National Inpatient Sample (NIS)

Introduction Burkitt Lymphoma (BL) is a highly aggressive B-cell non-Hodgkin Lymphoma, characterized by translocation and dysregulation of the MYC gene. BL comes in three distinct forms: endemic, sporadic, and immunodeficiency-related. BL has become a highly curable disease after the development of intense chemo-immunotherapy regimens, but given the low incidence of the disease, nationally representative studies on outcomes are scarce. We aim to highlight the most recent population-based factors associated with inpatient mortality and morbidity in patients with Burkitt's lymphoma. Methods The National Inpatient Sample database was queried from October 2015 to December 2020. Adults aged &amp;gt;= 18 with a primary diagnosis of BL were identified and stratified into those with and without the outcome of mortality. Complications included were queried using ICD codes most commonly found in the secondary diagnosis variables. Baseline characteristics, inpatient complications, and outcomes were compared using chi-squared and Wilcoxon rank-sum tests. Logistic regression analysis was performed to assess the risk of death before and after adjusting for multiple risk factors. Results We found 3,650 admissions with a primary diagnosis of BL, of which 320 (8.8%) patients died during the hospitalization. Patients who died had higher Charlson Comorbidity Index (CCI) &amp;gt;=3 (69%), tumor lysis syndrome (TLS) (41%), Sepsis (39%), and acute hypoxic respiratory failure (AHRF) (33%). No significant differences were found according to income, hospital bed-size or geographical region. In univariable analysis patients who died tended to be older with age &amp;gt;= 65 years (OR 2.55 (1.23 to 5.26) p=0.039), however, once adjusting for other variables there was no significant difference in mortality by age group, race, or gender. Multivariable analysis identified 3 factors with high association with mortality: acute renal failure (OR 3.07 (1.63 to 5.76), p&amp;lt;0.001), sepsis (OR 7.96 (3.85 to 16.4), p&amp;lt;0.001), and acute hypoxic respiratory failure (OR 2.70 (1.23 to 5.92), p=0.013). Conclusion BL remains a highly aggressive but potentially curable disease in patients able to tolerate intensive chemo-immunotherapy regimens. Our study highlights multiple factors that are independently associated with death include acute renal failure, sepsis, and acute hypoxic respiratory failure. Close monitoring should be placed on patients with the above complications to improve survival.

Improving Clinical Outcomes in APL: Weight Maintenance Strategies to Reduce Complications during Induction Therapy

Introduction: The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the treatment of acute promyelocytic leukemia (APL). However, despite a remission rate exceeding 96% and 5-year disease-free and overall survival rates reaching 96% and 88%, respectively, death during induction in clinical trials occurs in 4% of patients. Differentiation syndrome (DS) is a significant complication during ATRA and/or ATO induction therapy. The signs and symptoms of DS include dyspnea, unexplained fever, weight gain greater than 5 kg, unexplained hypotension, acute renal failure, and the presence of infiltrates and/or pleural/pericardial effusions on chest radiographs. The occurrence of 4 or more of these findings is considered diagnostic. In APL, patients are at risk for fluid overload secondary to multiple blood product transfusions and intravenous hydration. Acute hypoxic respiratory failure (AHRF) and septic shock are common indications for ICU admission in this patient population. At our institution, we monitored patients' daily weights intending to maintain the admission weights with diuresis or intravenous fluids as needed. We assessed the impact of maintaining euvolemia and daily weight monitoring to reduce the incidence of DS and ICU admissions among the APL patients treated at our institution. Methods: A retrospective chart review was conducted on 60 patients with APL who received treatment at our institution between 2016 and 2021. A total of 17 patients who were either not induced at our institution or did not have daily weight monitoring were omitted. Patient demographics, median age at diagnosis, hospitalization complications, ICU admission, and DS were analyzed. Patients were grouped based on if their daily weights were maintained at their admission level, plus or minus 3 kilograms. Only standing weights and weights before ICU transfer were considered. Results: Of the 43 patients who underwent induction therapy at our institution, 25.6% (n=11) had their weight maintained via diuresis and intravenous fluids, and none required ICU admission. Of the remaining 32 patients, 34.4% (n=11) were transferred to the ICU. Of the 11 patients transferred to the ICU, 6 were for AHRF, 2 were for septic shock, 1 was for adrenal insufficiency with vasopressor requirements, 1 was for subdural and epidural hemorrhage, and 1 was for intracranial hemorrhage. Maintaining euvolemia and weight within 3 kilograms of admission level correlated with fewer ICU admissions (OR = 0.085, 95% CI = 0.0046-1.5761) (p=0.0980). Of the 11 patients whose weights were followed and maintained, 9% (n=1) developed DS. Of the 32 patients who did not have their weights followed and maintained, 28% (n=9) met the criteria for DS (OR = 0.256, 95% CI = 0.028-2.296) (p=0.223). Conclusion: Volume overload is a significant concern in APL and its treatment. Our findings suggest that maintaining euvolemia and daily weight monitoring can lead to effective management of patients on the floor and may prevent unnecessary ICU transfers. Although there are limitations to the study due to its retrospective nature and low sample size, the cost-effectiveness and noninvasive methods of maintaining euvolemia support its potential addition to the standard treatment protocols. While maintaining euvolemia and monitoring daily weights is a simple intervention, it represents a promising strategy to improve the management of APL patients during induction therapy by decreasing the incidence of DS and ICU admissions. Further prospective studies are warranted to validate and expand upon these findings.

HLH Secondary to Influenza

Introduction Hemophagocytic lymphohistiocytosis (HLH) is a pathological condition characterized by excessive inflammation and tissue damage resulting from an aberrant immune system response. HLH can be classified into two distinct categories: primary HLH and secondary HLH. Secondary hemophagocytic lymphohistiocytosis (HLH) is an acquired condition that can be precipitated by various infections, malignancies, or rheumatological disorders. Herein, we present a rare case of HLH secondary to influenza B infection. Case Presentation A 37-year-old who routinely vapes and smokes cannabis presented to the emergency department with subjective fevers, body pains, fatigue, productive cough, shortness of breath, nausea, non-bloody, non-bilious vomiting, and watery diarrhea for one week. He was tachypneic, tachycardic, and febrile (101.1 F). He had loud bibasilar crackles on auscultation. Hb 14.8, total WBC 2.2, platelets 170, AKI with serum creatinine 1.9, and transaminitis with AST/ALT/ALP 130/56/122 U/L were the patient's initial lab results. Rapid influenza, strep, and COVID-19 antigen tests were negative. He exhibits hypoxemia with pH 7.46, pCO2 32.5, pO2 52.1, HCO3 22.9, and FIO2 40%. Urinalysis showed nonsignificant. CRP was 8.3 mg/dL. Negative procalcitonin. chest x-ray and ct showed bilateral diffuse patchy airspace infiltration, suggesting infectious process with mild pleaural effusion. In the critical care unit, he received Antibiotics and inhaled therapy for acute hypoxic respiratory failure with severe ARDS. After deteriorating, he was intubated. The respiratory pathogen panel detected Influenza B. Blood cultures and remaining pneumonia workup were negative. The lab results suggested HLH (table 1). Autoimmune tests were negative. Oseltamivir was given for 5 days. Repeat chest x-rays showed stable pulmonary infiltrates in the right middle and lower lobes, but the patient decompensated clinically with increasing ventilator requirements and dyssynchrony despite heavy sedation, paralytics, and proning and was transferred to a different hospital for ECMO evaluation on day 12. Discussion Primary and secondary HLH: Secondary HLH is caused by infections, malignancies, or rheumatological illnesses, while primary HLH is hereditary. The mortality outcome of HLH is extremely dependent on early detection and treatment 1. Due to the rarity of this disease entity, difficult diagnostic criteria, and concern for alternate diagnoses, internists may be less aware of it. Further complicating the diagnosis is the fact that the first bone marrow biopsy may not always show hemophagocytosis 2. This is why it is important to be cognizant of this diagnosis and it's diagnostic criteria. Our patient was suspected of HLH based on HScore for reactive hemophagocytic syndrome and the newest updated HLH diagnostic criteria (5 of 8 criteria should be met) 6. EBV is the most common viral infection which can cause HLH. CMV, Parvo, HSV, and H1N1 are other infections. HLH-Influenza B connection is poorly documented 7 Only one case of HLH induced by influenza B in a healthy patient was found in literature. To our knowledge, Our 38-year-old patient is the second known case of secondary HLH secondary to Influenza B in a healthy patient. Influenza B seldom causes HLH. This connection in adulthood is poorly researched. Patients with influenza virus infections have significant intestinal apoptosis and reactive hemophagocytic activity in bone marrow, lungs, and liver3. Influenza variants reduce CD8+ T cell cytotoxicity and perforin expression, likely causing HLH syndrome 4. A study suggests that virus-associated hemophagocytic syndrome (VAHS) is a common consequence of severe 2009 influenza A (H1N1) infection and contributes to multiorgan failure and mortality. 9 (36%) of 25 severely ill patients with confirmed 2009 influenza A (H1N1) infection developed VAHS, and 8 (89%) died 5. Conclusion: We present this case to raise awareness among physicians regarding the potential occurrence of hemophagocytic lymphohistiocytosis (HLH) as a complication in adult patients who present with influenza B virus infection accompanied by fever and pancytopenia. The aim is to emphasize the importance of considering HLH as a differential diagnosis in order to facilitate timely identification and initiation of appropriate treatment for this condition.

2599. Impact of Alveolar Neutrophilia on Outcomes in Patients with Suspected Ventilated Hospital-Acquired Bacterial Pneumonia

Abstract Background Ventilated hospital-acquired bacterial pneumonia (vHABP) is a major source of morbidity &amp; mortality in hospitalized patients. Clinical risk scores and systemic biomarkers have limited clinical &amp; prognostic utility in vHABP. Alveolar biomarkers—specifically alveolar neutrophilia (AN), the percentage of polymorphonuclear cells (PMN%) present in bronchoalveolar lavage (BAL) fluid—gauge the host inflammatory response directly at the site of infection, offering an attractive but untested predictive risk biomarker in vHABP. We aimed to generate preliminary data exploring AN as a vHABP biomarker. Methods We performed a retrospective cohort study of intensive care unit (ICU) patients with vHABP from 2010-2023. vHABP was defined as development of acute hypoxic respiratory failure requiring invasive mechanical ventilation, clinical suspicion of pneumonia by treating teams prompting performance of BAL respiratory culture, and BAL PMN% &amp;gt; 50%. Patient demographic characteristics, comorbidities and acute severity of illness metrics were abstracted via chart review. PMN% values were dichotomized using median split rounded to the nearest PMN% decile ( &amp;gt; or &amp;lt; 80% PMN% in BAL fluid). Study outcomes included ventilator-free days, ICU length of stay and vHABP-directed antibiotic treatment duration within 30 days of vHABP. Results 44 patients met study inclusion criteria. 30 (68%) had a BAL neutrophil of &amp;gt; 80%. Patients with BAL PMN &amp;gt; 80% had a numerically higher use of tracheostomy and trend towards lower P/F ratio at the time of vHABP diagnosis [Table 1]. BAL PMN &amp;gt; 80% was associated with a 15% decrease in ventilator-free days (p &amp;lt; 0.01) and a 25% longer ICU length of stay (p &amp;lt; 0.01) than those with BAL PMN &amp;lt; 80% [Figure 1]. There was no significant difference in post-BAL vHABP-directed antibiotic duration in patients with and without BAL PMN &amp;gt; 80%. Conclusion Though limited by low sample size, this exploratory study suggests AN may be a potentially useful predictive risk biomarker in vHABP. Larger-scale, prospective studies of alveolar biomarkers—including AN—in vHABP are warranted. Disclosures Owen Albin, MD, Charles River Laboratories: Advisor/Consultant|Shionogi: Advisor/Consultant

Abstract 12855: Early vs. Late Transcatheter Aortic Valve Replacement in Acute Heart Failure Hospitalizations: National Inpatient Sample (2015-2020)

Introduction: Data on clinical outcomes of early transcatheter aortic valve replacement (TAVR) (&lt;48 hours) compared to late (≥48 hours) TAVR in patients hospitalized with acute heart failure (AHF) and aortic stenosis (AS) remains limited. We aim to evaluate the differences between early vs. late TAVR regarding major clinical outcomes using a real-world US database. Hypothesis: There is no differences in the clinical outcomes based on the timing of TAVR procedural intervention in patients with acute heart failure. Methods: We used the National Inpatient Sample database by utilizing ICD-10 codes to identify all hospitalizations with a diagnosis of AHF and TAVR (2015-2020). The associations between the time of TAVR and outcomes were examined using multivariable logistic regression. Propensity-score matched (PSM) analysis was utilized to determine the adjusted odds ratio (aOR) of major clinical outcomes. Results: A total of 25,285 weighted hospitalizations of AHF were identified, of which 6,855 patients (27.1%) underwent early TAVR and 18,430 (72.9%) had late TAVR. Compared with early TAVR, Late TAVR was associated with less need for mechanical circulatory support (MCS) (aOR 0.97 [0.96-0.98], p&lt;0.01) and acute hypoxic respiratory failure (aOR 0.99 [0.98-0.99], p&lt;0.01), but higher odds of developing septic shock (aOR 2.06 [1.52-2.80], p &lt;0.01). However, there was no significant difference between both procedures regarding in-hospital mortality (aOR 1.01 [1.00-1.02], p=0.14), cardiac arrest (aOR 0.99 [0.98-1.00], p=0.21), and stroke (aOR 1.01 [1.00-1.02], p=0.18). Conclusions: Most patients with AHF and AS undergo TAVR after 48 hours of their presentation. After PSM, there was no difference in inpatient mortality, cardiac arrest, and stroke between both procedures. Late TAVR was associated with lower odds for MCS and acute hypoxic respiratory failure. The optimal timing of TAVR in patients with AHF and AS needs further study.

Abstract 19124: Systemic Sclerosis Masquerading as Heart Failure

Cardiac disease occurs in 80% of patients with systemic sclerosis (SS). Patients may present with various symptoms, including dyspnea, palpitations, chest pain, and heart failure. Of these, systolic heart failure has the rarest prevalence, estimated between 1-5% of patients. The mechanism behind myocardial damage is still unclear. Current literature supports a fibrotic process due to ischemic necrosis and reperfusion damage. There is a lack of representation of SS-related cardiac disease, but it is crucial to recognize it early for prompt intervention. A 62-year-old male with a history of diastolic dysfunction presented with acute hypoxic respiratory failure. A transthoracic echocardiogram demonstrated a new severely reduced systolic function at 20%. Angiogram demonstrated non-obstructive coronary artery disease. Further autoimmune workup revealed a significantly elevated ANA and highly positive RNA polymerase III antibody. The patient underwent a cardiac magnetic resonance imaging (MRI) scan, which showed evidence of inflammation with diffuse myocardial fibrosis concerning an infiltrative process. Subsequent cardiac positron emission tomography (PET) showed increased uptake in the basal portions of the septum and anterior wall for myocarditis. Given his autoimmune workup results and imaging, the patient was subsequently diagnosed with rapidly progressive cutaneous systemic sclerosis and associated non-ischemic cardiomyopathy. The patient was started on goal-directed medical therapy, including losartan, spironolactone, metoprolol, and empagliflozin. Additionally, he started on mycophenolate mofetil for immunosuppression. Roughly six months after discharge, his pulmonary function tests remain stable. His ejection fraction improved to 62%. Roughly one-third of systemic sclerosis-related deaths are due to cardiac involvement. Yet, most patients are asymptomatic during the early stages, with a variable phenotype later in disease progression. We report a case of a patient who developed systemic sclerosis-related myocarditis with an initial presentation of acute systolic heart failure. His cardiac dysfunction recovered from optimal goal-directed therapy and immunosuppression.

Abstract 15757: Racial Disparities in Acute Respiratory Failure Incidence During Hypertensive Emergencies

Introduction: One of the most frequent complications of hypertensive emergency is pulmonary edema, which can ultimately lead to requiring mechanical ventilation because of respiratory failure. Additionally, epidemiologic studies have observed that certain races are disproportionately affected by hypertensive emergency. This analysis aimed to assess if race was also associated with increased likelihood of requiring mechanical ventilation during hypertensive emergencies. Methods: Using the 2020 National Inpatient Sample data, we identified patients admitted due to hypertensive emergencies. We excluded admissions for primary acute hypoxic respiratory failure necessitating invasive mechanical ventilation. To explore potential relationships, we employed logistic and linear regression analyses, accounting for potential confounders. We deemed the results as statistically significant when the 2-tailed p-value was &lt;0.05. Results: In 2020, among 1,221,535 hypertensive emergency hospital admissions, 124,200 (10.2%) involved patients needing mechanical ventilation due to respiratory failure. After adjusting for factors such as age, gender, hospital attributes, insurance, income, and Elixhauser comorbidities, Black and Asian/Pacific Islander patients exhibited higher likelihoods of requiring mechanical ventilation due to respiratory failure. Compared to White patients, the adjusted odds ratios were 1.06 (95% CI 1.05-1.12) for Black patients and 1.18 (95% CI 1.06-1.32) for Asian/Pacific Islander patients. Conclusions: We have demonstrated that there are racial disparities associated with development of acute hypoxic respiratory failure in the setting of hypertensive emergencies. Further research needs to be undertaken to identify if these racial differences are due to differences in blood pressure control or if clinical management differs by race in the acute hospitalization contributing to adverse outcomes.

Alveolar Hyperoxia and Exacerbation of Lung Injury in Critically Ill SARS-CoV-2 Pneumonia.

Acute hypoxic respiratory failure (AHRF) is a prominent feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) critical illness. The severity of gas exchange impairment correlates with worse prognosis, and AHRF requiring mechanical ventilation is associated with substantial mortality. Persistent impaired gas exchange leading to hypoxemia often warrants the prolonged administration of a high fraction of inspired oxygen (FiO2). In SARS-CoV-2 AHRF, systemic vasculopathy with lung microthrombosis and microangiopathy further exacerbates poor gas exchange due to alveolar inflammation and oedema. Capillary congestion with microthrombosis is a common autopsy finding in the lungs of patients who die with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome. The need for a high FiO2 to normalise arterial hypoxemia and tissue hypoxia can result in alveolar hyperoxia. This in turn can lead to local alveolar oxidative stress with associated inflammation, alveolar epithelial cell apoptosis, surfactant dysfunction, pulmonary vascular abnormalities, resorption atelectasis, and impairment of innate immunity predisposing to secondary bacterial infections. While oxygen is a life-saving treatment, alveolar hyperoxia may exacerbate pre-existing lung injury. In this review, we provide a summary of oxygen toxicity mechanisms, evaluating the consequences of alveolar hyperoxia in COVID-19 and propose established and potential exploratory treatment pathways to minimise alveolar hyperoxia.