Clinical perspectives in bronchiectasis management.

Non-cystic fibrosis bronchiectasis is a chronic inflammatory airway disease that results in permanent lung damage and can correlate with considerable clinical and economic burden. There are gaps in knowledge surrounding bronchiectasis, for which there are no published US-based treatment guidelines or FDA-approved therapies. Given the current challenges and gaps in care, the authors of this article convened for an AJMC® roundtable in March 2024. This publication summarizes the main findings of that roundtable and situates them in a scholarly context. Panelists agreed that patients with unexplained chronic cough or fatigue, purulent sputum production, hemoptysis, or repeated infection should undergo CT scanning to assess the presence of bronchiectasis, which has been estimated to affect approximately 364,000 to 558,000 individuals at least 18 years of age. They noted that disease symptoms and treatment burden can considerably diminish patient health-related quality of life (HRQOL) and that an exacerbation uniformly signifies deteriorating health and substantially impacts disease progression, hospitalization rates, and mortality. Absent an FDA-approved therapy, panelists' top management priorities were preventing or reducing exacerbations and maintaining or improving HRQOL. Panelists concluded that providers are ill-equipped to change the course of this heterogenous disease and that there is a real need for options to manage symptoms, for US-based guidelines, and for more research into epidemiology, etiology, and treatment.

Pharmacokinetic variability of CFTR modulators from standard and alternative regimens.

Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.

Dataset of thermographic images for the detection of buried landmines.

This article presents a dataset of thermographic images of terrain with antipersonnel mines to identify the presence or absence of these artifacts using machine learning and artificial vision techniques. The dataset has 2700 thermographic images acquired at different heights, using a Zenmuse XT infrared camera (7-13 µm), embedded in the DJI Matrice 100 drone. The data acquisition experiment consists of capturing aerial infrared images of a terrain where elements with characteristics similar to antipersonnel mines type legbreaker were buried. The mines were planted in the ground between 0 cm and 10 cm deep and were spread over an area of 10 m x 10 m. The drone used a flight protocol that set the trajectory, the time of the flight, the acquisition height, and the image sampling frequency. This dataset was used in "Detection of "legbreaker" antipersonnel landmines by analysis of aerial thermographic images of the soil" [7].

Towards development of evidence to inform recommendations for the evaluation and management of bronchiectasis.

Bronchiectasis (BE) is a chronic condition characterized by airway dilation as a consequence of a variety of pathogenic processes. It is often associated with persistent airway infection and an inflammatory response resulting in cough productive of purulent sputum, which has an adverse impact on quality of life. The prevalence of BE is increasing worldwide. Treatment guidelines exist for managing BE, but they are generally informed by a paucity of high-quality evidence. This review presents the findings of a scientific advisory board of experts held in the United States in November 2020. The main focus of the meeting was to identify unmet needs in BE and propose ways to identify research priorities for the management of BE, with a view to developing evidence-based treatment recommendations. Key issues identified include diagnosis, patient evaluation, promoting airway clearance and appropriate use of antimicrobials. Unmet needs include effective pharmacological agents to promote airway clearance and reduce inflammation, control of chronic infection, clinical endpoints to be used in the design of BE clinical trials, and more accurate classification of patients using phenotypes and endotypes to better guide treatment decisions and improve outcomes.

Inhaled nitric oxide for adults with pulmonary non-tuberculous mycobacterial infection.

QUESTION: There is an increasing prevalence of nontuberculous mycobacteria pulmonary disease (NTM-PD) in the US. Treatment of NTM-PD typically requires multiple medications, which can be associated with unpleasant morbidity and eradication of infection is difficult. Therefore, there is a critical need for novel effective and well-tolerated therapies. Recent in vitro data and case reports have suggested that nitric oxide, inhaled as a gas (gNO), has antimicrobial activity against NTM. We sought to investigate the effect of gNO in patients with NTM-PD in an open-label proof of concept trial. METHODS: Eligible participants had NTM-PD with persistently positive respiratory cultures for NTM even if on antibiotic treatment. Participants were treated with gNO for 50 min three times daily, five days per week, for three weeks (total of 15 treatment days). RESULTS: Ten participants, of whom nine were on long-term NTM antibiotic therapy, were enrolled. All participants completed the regimen without interruption or discontinuation. Small increases in methemoglobin were noted during treatment, and all resolved to baseline within 2 h. Four participants (40%) met the primary outcome measure of negative sputum cultures after three weeks of therapy. Following treatment discontinuation, three of these participants were again culture positive during the 3-month post-treatment monitoring period, although with measures suggesting low bacterial burden. ANSWER: Patients tolerated a 3-week regimen of gNO without safety concerns, and despite highly refractory disease four individuals completed the study with negative cultures, although three were again positive in subsequent months. These data support further investigation of gNO as a potential therapy for NTM-PD.

What the future holds: cystic fibrosis and aging.

Cystic fibrosis (CF) is one of the most common genetic diseases with around 70,000 affected patients worldwide. CF is a multisystem disease caused by a mutation in the CF transmembrane conductance regulator gene, which has led to a significant decrease in life expectancy and a marked impairment in the quality of life for people with CF (pwCF). In recent years, the use of highly effective CFTR modulator therapy (HEMT) has led to improved pulmonary function, fewer CF exacerbations, lower symptom burden, and increased weight. This has coincided with an increased life expectancy for pwCF, with mean age of survival being now in the 50s. This being a major breakthrough, which the CF population has hoped for, pwCF are now facing new challenges by growing old with a chronic respiratory disease. In this mini review, we are attempting to summarize the current knowledge of the aging process and its effect on CF disease and its manifestations including new developments, the current research gaps and potential future developments in the field to allow healthy aging for the CF community.

Time-to-positivity of Mycobacterium avium complex in broth culture associates with culture conversion.

BACKGROUND: Mycobacterial time to positivity (TTP) in liquid culture media has predictive value for longer term outcomes in pulmonary tuberculosis, but has not been thoroughly studied in nontuberculous mycobacterial pulmonary disease. This study sought to evaluate for association between TTP and sputum culture conversion to negative in pulmonary disease caused by Mycobacterium avium complex (MAC). METHODS: Data from the CONVERT trial (NCT02344004) that evaluated efficacy of guideline-based-therapy with or without amikacin liposome inhalation suspension in adults with refractory MAC-PD (Mycobacterium avium complex pulmonary disease) were analyzed. We evaluated TTP measures for sputum obtained prior to study treatment initiation and at monthly visits, assessing reproducibility of measures as well as association of TTP with culture conversion on treatment. RESULTS: Data from 71 participants with at least one screening visit TTP value were analyzed. For participants who provided more than one sputum sample at a given visit, there was moderate between-sample reliability, with median intraclass correlation coefficient 0.62 (IQR 0.50, 0.70). Median TTP at screening was longer in those participants who subsequently achieved vs. did not achieve culture conversion (10.5 [IQR 9.4] days vs. 4.2 [IQR 2.8] days, p = 0.0002). Individuals with culture conversion by study treatment month 6 were more likely to have a screening TTP > 5 days compared to those who did not achieve culture conversion (OR 15.4, 95% CI 1.9, 716.7, p = 0.0037) and had increasing TTPs over time. CONCLUSIONS: TTP prior to and on treatment is associated with microbiological treatment response in patients with MAC-PD.

Poly (acetyl, arginyl) glucosamine disrupts Pseudomonas aeruginosa biofilms and enhances bacterial clearance in a rat lung infection model.

Pseudomonas aeruginosa is a common opportunistic pathogen that can cause chronic infections in multiple disease states, including respiratory infections in patients with cystic fibrosis (CF) and non-CF bronchiectasis. Like many opportunists, P. aeruginosa forms multicellular biofilm communities that are widely thought to be an important determinant of bacterial persistence and resistance to antimicrobials and host immune effectors during chronic/recurrent infections. Poly (acetyl, arginyl) glucosamine (PAAG) is a glycopolymer that has antimicrobial activity against a broad range of bacterial species, and also has mucolytic activity, which can normalize the rheological properties of cystic fibrosis mucus. In this study, we sought to evaluate the effect of PAAG on P. aeruginosa bacteria within biofilms in vitro, and in the context of experimental pulmonary infection in a rodent infection model. PAAG treatment caused significant bactericidal activity against P. aeruginosa biofilms, and a reduction in the total biomass of preformed P. aeruginosa biofilms on abiotic surfaces, as well as on the surface of immortalized cystic fibrosis human bronchial epithelial cells. Studies of membrane integrity indicated that PAAG causes changes to P. aeruginosa cell morphology and dysregulates membrane polarity. PAAG treatment reduced infection and consequent tissue inflammation in experimental P. aeruginosa rat infections. Based on these findings we conclude that PAAG represents a novel means to combat P. aeruginosa infection, and may warrant further evaluation as a therapeutic.

Abdominal Surgical Procedures in Adult Patients With Cystic Fibrosis: What Are the Risks?

BACKGROUND: With advances in medical care, patients with cystic fibrosis are more commonly living into adulthood, yet there are limited data describing the need for GI surgery and its outcomes in adult cystic fibrosis patients. OBJECTIVE: We aim to use a national administrative database to evaluate trends in abdominal GI surgery and associated postoperative outcomes among adult cystic fibrosis patients. DESIGN: This was a national retrospective cohort study. SETTING: A national all-payor administrative database from 2000 to 2014 was used. PATIENTS: Patients included adults (age ≥18 years) with cystic fibrosis undergoing abdominal GI surgery. MAIN OUTCOME MEASURES: The primary outcome was trend over time in number of surgical admissions. Secondary outcomes included morbidity and mortality by procedure type. RESULTS: We identified 3075 admissions for abdominal surgery, of which 28% were elective. Major GI surgical procedures increased over the study period ( p < 0.01), whereas appendectomy and cholecystectomy did not demonstrate a clear trend ( p = 0.90). The most common procedure performed was cholecystectomy ( n = 1280; 42%). The most common major surgery was segmental colectomy ( n = 535; 18%). Obstruction was the most common surgical indication ( n = 780; 26%). For major surgery, in-hospital mortality was 6%, morbidity was 37%, and mean length of stay was 15.9 days (SE 1.2). LIMITATIONS: The study is limited by a lack of granular physiological and clinical data within the administrative data source. CONCLUSIONS: Major surgical admissions for adult patients with cystic fibrosis are increasing, with the majority being nonelective. Major surgery is associated with significant morbidity, mortality, and prolonged length of hospital stay. These findings may inform perioperative risk for adult patients with cystic fibrosis in need of GI surgery. See Video Abstract at http://links.lww.com/DCR/B850 . PROCEDIMIENTOS QUIRRGICOS ABDOMINALES EN PACIENTES ADULTOS CON FIBROSIS QUSTICA CULES SON LOS RIESGOS: ANTECEDENTES:Con los avances en la medicina, los pacientes con fibrosis quística viven más comúnmente hasta la edad adulta, pero hay datos escasos que describan la necesidad de cirugía gastrointestinal y sus resultados en pacientes adultos con fibrosis quística.OBJETIVO:Nuestro objetivo es utilizar una base de datos administrativa nacional para evaluar las tendencias en la cirugía gastrointestinal abdominal y los resultados posoperatorios asociados entre los pacientes adultos con fibrosis quística.DISEÑO:Estudio de cohorte retrospectivo nacional.AJUSTE:Base de datos administrativa nacional de todas las instituciones pagadoras desde 2000 a 2014.PACIENTES:Todos los pacientes adultos (edad> 18) con fibrosis quística sometidos a cirugía gastrointestinal abdominal.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la tendencia a lo largo del tiempo en el número de ingresos quirúrgicos. Los resultados secundarios incluyeron morbilidad y mortalidad por tipo de procedimiento.RESULTADOS:Identificamos 3.075 ingresos por cirugía abdominal de los cuales el 28% fueron electivos. Los procedimientos quirúrgicos gastrointestinales mayores aumentaron durante el período de estudio (p <0,01) mientras que la apendicectomía y la colecistectomía no demostraron una tendencia clara (p = 0,90). El procedimiento realizado con mayor frecuencia fue la colecistectomía (n = 1.280; 42%). La cirugía mayor más común fue la colectomía segmentaria (n = 535; 18%). La obstrucción fue la indicación quirúrgica más común (n = 780; 26%). Para la cirugía mayor, la mortalidad hospitalaria fue del 6%, la morbilidad del 37% y la estadía media de 15,9 días (EE 1,2).LIMITACIONES:El estudio está limitado por la falta de datos clínicos y fisiológicos granulares dentro de la fuente de datos administrativos.CONCLUSIONES:Los ingresos quirúrgicos mayores de pacientes adultos con fibrosis quística están aumentando y la mayoría no son electivos. La cirugía mayor se asocia con una morbilidad y mortalidad significativas y una estancia hospitalaria prolongada. Estos hallazgos pueden informar el riesgo perioperatorio para pacientes adultos con fibrosis quística que necesitan cirugía gastrointestinal. Consulte Video Resumen en http://links.lww.com/DCR/B850 . (Traducción-Dr. Felipe Bellolio ).

Chest Computed Tomography Features of Nontuberculous Mycobacterial Pulmonary Disease Versus Asymptomatic Colonization: A Cross-sectional Cohort Study.

BACKGROUND: Asymptomatic colonization by nontuberculous mycobacteria (NTM) found in sputum isolates are commonly encountered and clinicians lack a biomarker for prognosticating the risk of transition asymptomatic colonization to active clinical disease. Chest computed tomography (CT) imaging is commonly obtained in this patient population and may serve a role for this purpose. METHODS: We conducted a single-center, cross-sectional study of patients followed in the NTM clinic at our center between August 2019 and August 2020. All patients had a history of NTM isolated from their airways and were cohorted as either nontuberculous mycobacteria-pulmonary disease (NTM-PD) if they met ATS/IDSA guidelines for treatment or as nontuberculous mycobacteria-colonized (NTM-C) if they did not meet ATS/IDSA criteria for NTM treatment. Patients with a chest CT were included in the analysis and CT scans were assessed for features including bronchiectasis, nodules, and cavities. Bronchiectasis severity was calculated using the modified Reiff scoring system. Univariate analyses were conducted to compare patients with NTM-C and NTM-PD. RESULTS: Eighty-four patients were included in the analysis and 27 were classified as NTM-C and 57 as NTM-PD. NTM-PD patients had a greater median number of lung lobes affected by bronchiectatic airways (6 [1] NTM-PD vs. 5 [3] NTM-C P=0.005) and a greater frequency of cystic bronchiectasis (17.5% NTM-PD vs. 0% NTM-PD, P=0.016). Bronchiectasis severity was higher for NTM-PD patients (7 [9] NTM-PD vs. 5 [1.5] NTM-C, P<0.001). CONCLUSIONS: Patients with NTM-PD have greater bronchiectatic airway involvement and the forms of bronchiectasis present are more severe compared with NTM-C patients. In addition, cavitation of lung parenchyma was a radiographic feature solely associated with NTM-PD. Features identified on chest CT may be useful as a prognostic biomarker for the risk of transition from NTM-C to NTM-PD.

Elexacafator/tezacaftor/ivacaftor resolves subfertility in females with CF: A two center case series.

Infertility and subfertility are commonly faced by females with cystic fibrosis (FwCF) and resulting in decreased contraceptive use and increased utilization of reproductive technologies. Elexacaftor-tezacaftor-ivacaftor (ETI) is a CFTR modulator that affects common causes of subfertility. Two CF centers conducted a retrospective chart review on females with CF who were receiving ETI and became pregnant. We analyzed obstetrical-gynecological history, genotype, and clinical response to ETI therapy. Fourteen FwCF on ETI became pregnant. Half (7) of the FwCFs were previously attempting to conceive, but only three were using contraceptives. Four FwCF had a history of infertility; two were reconsidering use of reproductive technologies (IUI). Patients achieved conception at mean 8 weeks after initiating ETI. ETI may lessen CF-associated factors that affect fertility; however, its exact mechanism is unknown. This warrants counseling on contraceptive use and family planning prior to initiation of therapy and at routine intervals while utilizing ETI.

Parasite density in severe malaria in Colombia.

BACKGROUND: Colombia has officially adopted the parasite density levels of severe malaria established by the WHO (>50,000 parasites/µl). These values have been inferred from areas of high transmission in Africa and are not consistent with the dynamics of low and unstable transmission in Colombia. The objective of this study was therefore to determine the parasite density values observed in patients with severe malaria and their distribution in the different ecoepidemiological regions of Colombia. METHODS: A retrospective and descriptive study of confirmed cases of severe malaria was conducted in endemic areas of malaria in Colombia over the period 2014-2017. Data were collected from secondary sources of the Subnational Programs of Malaria Prevention and Control. Person, place, and time variables were selected. The official definition of severe malaria was adopted, and compliance with these criteria was determined. Univariate and bivariate analyses were conducted with absolute and relative frequency measures, and the relevant statistical tests were applied. RESULTS: The overall parasite density values in Colombia showed a geometric mean of 5,919 parasites/µl (95% CI: 5,608-6,248). By parasite species, the values were 6,151 (95% CI: 5,631-6,718) for Plasmodium falciparum and 5,815 (95% CI: 5,428-6,230) for Plasmodium vivax. The highest parasite density values were recorded in the Amazon ecoepidemiological region (8,177; 95% CI: 6,015-11,116), and the lowest values were recorded in the Andean region (5,026; 95% CI: 2,409-10,480). CONCLUSIONS: In endemic areas of low and unstable malaria transmission in the Colombian territory, the parasite density levels observed in populations with severe malaria are lower than the officially established values. The parasite density criterion is not really a relevant criterion for the definition of severe cases in Colombia and it certainly not be used to make a clinical decision about the severity of the disease.

The complete mitochondrial and plastid genomes of the invasive marine red alga Caulacanthus okamurae (Caulacanthaceae, Rhodophyta) from Moss Landing, California, USA.

Caulacanthus okamurae is an invasive red alga that forms extensive mats in sheltered marine habitats around the world. To determine its genomic structure and genetic relationship to native and other non-native populations of C. okamurae, high-throughput sequencing analysis was performed on an introduced specimen from Bennett Slough, Moss Landing, California, USA. Assembly of 23,146,595 filtered 150 bp paired-end Illumina sequencing reads yielded its complete mitogenome (GenBank accession MT193839) and plastid genome (GenBank accession MT193838). The mitogenome is 25,995 bp in length and contains 50 genes. The plastid genome is 173,516 bp and contains 234 genes. Comparison of the organellar chromosomes to other Gigartinales revealed a high-level of gene synteny. BLAST analysis of marker sequences (rbcL, cox1, cox2) of C. okamurae from Moss Landing identified four identical DNA sequences: one from a specimen from a native population of C. okamurae from South Korea and three from specimens representing invasive populations from France, Spain, and the USA. These genetic results confirm the presence of C. okamurae in central California, USA, and represent the first complete mitogenome and plastid genome from the Caulacanthaceae.

Pulmonary Complications of Cystic Fibrosis.

Cystic fibrosis (CF) lung disease is characterized by the development of progressive bronchiectasis and impaired lung function with severe airflow obstruction. CF patients suffer from shortened life expectancy, primarily driven by respiratory failure. The mechanism by which CF lung disease develops is the result of an interplay of multiple intrinsic and extrinsic factors including genotype, abnormalities in mucus composition and movement, chronic inflammation, and chronic airway infection. Although all CF patients are at increased risk for pulmonary complications including hemoptysis, pneumothorax, pulmonary hypertension, and chronic hypoxic and hypercapnic respiratory failure, the risk of developing these complications increases with progression of lung disease. The focus of this article is to summarize the pathophysiology, epidemiology, and management of these key pulmonary complications.

A glycopolymer improves vascoelasticity and mucociliary transport of abnormal cystic fibrosis mucus.

Cystic fibrosis (CF) is characterized by increased mucus viscosity and delayed mucociliary clearance that contributes to progressive decline of lung function. Mucus in the respiratory and GI tract is excessively adhesive in the presence of airway dehydration and excess extracellular Ca2+ upon mucin release, promoting hyperviscous, densely packed mucins characteristic of CF. Therapies that target mucins directly through ionic interactions remain unexploited. Here we show that poly (acetyl, arginyl) glucosamine (PAAG), a polycationic biopolymer suitable for human use, interacts directly with mucins in a Ca2+-sensitive manner to reduce CF mucus viscoelasticity and improve its transport. Notably, PAAG induced a linear structure of purified MUC5B and altered its sedimentation profile and viscosity, indicative of proper mucin expansion. In vivo, PAAG nebulization improved mucociliary transport in CF rats with delayed mucus clearance, and cleared mucus plugging in CF ferrets. This study demonstrates the potential use of a synthetic glycopolymer PAAG as a molecular agent that could benefit patients with a broad array of mucus diseases.

Clinical Outcomes of Paramyxovirus Infections in Lung Transplant Recipients Treated With Oral Ribavirin: A Two-Center Case Series.

OBJECTIVES: Paramyxoviruses contribute to morbidity and mortality after lung transplant and are associated with bronchiolitis obliterans syndrome. Oral ribavirin has been used off-label for treatment of paramyxoviruses in immunosuppressed patients; however, data supporting its use for this purpose are lacking. MATERIALS AND METHODS: We conducted a retrospective review to evaluate clinical outcomes of lung transplant recipients infected with paramyxoviruses and received treatment with oral ribavirin at 2 tertiary referral centers. Patients who were diagnosed with paramyxovirus infection by polymerase chain reaction testing between January 2011 and December 2014 and who received oral ribavirin were included. Clinical outcomes included pulmonary function testing, infection severity, and adverse events related to treatment. RESULTS: Twenty-six patients were diagnosed with a paramyxovirus and received oral ribavirin. The changes in mean forced expiratory volume 1 second from preinfection to infection onset and from infection onset to postinfection were significant (1.79 ± 0.13 to 1.61 ± 0.12 L and 1.61 ± 0.12L to 1.74 ± 0.12 L; P = .0001). Similar results were seen in subgroup analysis when respiratory syncytial virus and parainfluenza infections were evaluated independently. CONCLUSIONS: Use of oral ribavirin for treatment of paramyxovirus infections in lung transplant recipients was safe and associated with recovery of lung function.

Implementation of a successful eradication protocol for Burkholderia Cepacia complex in cystic fibrosis patients.

BACKGROUND: Infection with Burkholderia cepacia complex (Bcc) results in a heterogeneous clinical course ranging from asymptomatic colonization of the airways to fulminant respiratory failure in patients with cystic fibrosis (CF). Early eradication of Pseudomonas aeruginosa improves clinical outcomes. The efficacy and clinical outcomes following implementation of an eradication protocol for Bcc are less well understood. METHODS: We developed and implemented a single center Bcc eradication protocol that included an intensive combination of intravenous, inhaled, and oral antibiotic therapies based on in vitro sensitivities. We conducted a retrospective cohort analysis of clinical outcomes compared to patients with chronic Bcc infection. RESULTS: Six patients were identified as having a newly acquired Bcc colonization and were placed on the eradication protocol. Sequential sputum samples after completion of the protocol demonstrated sustained clearance of Bcc in all patients. Lung function and nutritional status remained stable in the year following eradication. CONCLUSION: Clearance of Bcc from sputum cultures using a standardized protocol was successful at one year and was associated with clinical stability.

Lactate kinetics in sepsis and septic shock: a review of the literature and rationale for further research.

Over the last two decades, there have been vast improvements in sepsis-related outcomes, largely resulting from the widespread adoption of aggressive fluid resuscitation and infection control. With increased understanding of the pathophysiology of sepsis, novel diagnostics and resuscitative interventions are being discovered. In recent years, few diagnostic tests like lactate have engendered more attention and research in the sepsis arena. Studies highlighting lactate's prognostic potential for mortality and other outcomes are ubiquitous and largely focus on the early stage of sepsis management, defined as the initial 6 h and widely referred to as the "golden hours." Additional investigations, although more representative of surgical and trauma patients, suggest that lactate measurements beyond 24 h from the initiation of resuscitation continue to have predictive and prognostic utility. This review summarizes the current research and evidence regarding lactate's utility as a prognosticator of clinical outcomes in both early and late sepsis management, defines the mechanism of lactate production and clearance, and identifies areas warranting further research.

Acute Fibrinous Organizing Pneumonia: A Case Report and Literature Review.

Acute fibrinous organizing pneumonia (AFOP) is a distinct histopathologic pattern of lung injury with the hallmark feature of intra-alveolar fibrin deposits with associated organizing pneumonia, type II pneumocyte hyperplasia, and a patchy lymphohistiocytic proliferation. We describe the case of a previously healthy 47-year-old man who presented with a 4-day history of worsening dyspnea, cough, and nocturnal fevers and miliary nodules on chest imaging. Subsequently, there was an indication of AFOP when he underwent open lung biopsy. AFOP has been associated with a variety of underlying conditions including rheumatologic diseases, medications, and infections, and several cases were idiopathic. This case highlights the importance for radiologists to be aware of this uncommon pattern of lung injury and to consider it in the differential when encountering bilateral miliary infiltrates on chest imaging.