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The clinical course of severe COVID-19 in cystic fibrosis (CF) is incompletely understood. We describe the use of alpha-1 antitrypsin (AAT) as a salvage therapy in a critically unwell patient with CF (PWCF) who developed COVID-19 while awaiting lung transplantation.

IV AAT was administered at 120mg/kg/week for 4 consecutive weeks. Levels of interleukin (IL)-1β, IL-6, IL-8, and soluble TNF receptor 1 (sTNFR1) were assessed at regular intervals in plasma, with IL-1β, IL-6, IL-8 and neutrophil elastase (NE) activity measured in airway secretions. Levels were compared to baseline and historic severe exacerbation measurements.

Systemic and airway inflammatory markers were increased compared to both prior exacerbation and baseline levels, in particular IL-6, IL-1β and NE activity. Following each AAT dose, rapid decreases in each inflammatory parameter were observed. These were matched by marked clinical and radiographic improvement.

The results support further investigation of AAT as a COVID-19 therapeutic, and re-exploration of its use in CF.

The results support further investigation of AAT as a COVID-19 therapeutic, and re-exploration of its use in CF.

Two functional measurements (multiple breath washout [MBW] and hyperpolarized

Xe ventilation magnetic resonance imaging [

Xe MRI]) have been shown to be more sensitive to cystic fibrosis (CF) lung obstruction than traditional spirometry. However, functional techniques may be sensitive to different underlying structural abnormalities. The purpose of this study was to determine relationships between these functional markers, their pathophysiology, and 1-year clinical outcomes.

Spirometry, MBW,

Xe MRI, and ultrashort echo-time (UTE) MRI were obtained in a same-day assessment of 27 pediatric CF patients (ages 11.5±5.0) who had not begun CFTR modulator therapies. UTE MRI was scored for structural abnormalities and functional metrics obtained via spirometry, MBW and

Xe MRI. 1-year outcomes (ΔFEV

and pulmonary exacerbations), during which ≈50% initiated modulator therapy, were obtained from the electronic medical record.

MBW,

Xe MRI, and UTE MRI detected clinically significant disease in more subjects (>78%) compared to spirometry (<30%). UTE MRI suggests increased odds of bronchial changes when mucus plugging is present in the same lobe. MBW and

Xe MRI correlated best with mucus plugging, while spirometry correlated best with consolidations. Bronchial abnormalities were associated with future pulmonary exacerbations.

MBW,

Xe MRI, and UTE MRI are more sensitive for detection of pediatric CF lung disease when compared to spirometry. MBW and

Xe MRI correlated with structural abnormalities which occur in early CF disease, suggesting MBW and

Xe MRI are valuable tools in mild CF lung disease that can guide clinical decision making.

MBW, 129Xe MRI, and UTE MRI are more sensitive for detection of pediatric CF lung disease when compared to spirometry. MBW and 129Xe MRI correlated with structural abnormalities which occur in early CF disease, suggesting MBW and 129Xe MRI are valuable tools in mild CF lung disease that can guide clinical decision making.Lipids have emerged as important actors in an ever-growing number of key functions in cell biology over the last few years. Among them, glycerophospholipids are major constituents of cellular membranes. Because of their amphiphilic nature, phospholipids form lipid bilayers that are particularly useful to isolate cellular content from the extracellular medium, but also to define intracellular compartments. Interestingly, phospholipids come in different flavors based on their fatty acyl chain composition. Indeed, lipidomic analyses have revealed the presence in cellular membranes of up to 50 different species of an individual class of phospholipid, opening the possibility of multiple functions for a single class of phospholipid. In this review we will focus on phosphatidic acid (PA), the simplest phospholipid, that plays both structural and signaling functions. Among the numerous roles that have been attributed to PA, a key regulatory role in secretion has been proposed in different cell models. We review here the evidences that support the idea that mono- and poly-unsaturated PA control distinct steps in hormone secretion from neuroendocrine cells.

Several different flaps can reconstruct intraoral defects or lower limb deficits after free fibula osteo-cutaneous flap harvesting for jaw reconstructions. However, commonly used options may not be available for various reasons and can be associated with significant morbidity. We hypothesized that flaps supplied by the superficial peroneal nerve accessory artery (SPNAA) could be a viable alternative reconstructive option.

We describe the SPNAA's anatomy using 20 human cadaveric leg dissections and report eight cases involving SPNAA-based perforator flap reconstructions (six propeller flaps and two free flaps) in a retrospective case series. Patient-specific baseline variables and intraoperative and postoperative outcomes are described.

Cadaveric dissection suggests that the location of the SPNAA is reliable but its origin varies, with 40% (N = 8) of SPNAAs being of type I origin, 20% type II (N = 4), and 40% (N = 8) type III in our series. All reconstructions were successful. No intraoperative complications occurred during propeller or free-flap reconstructions. No flap failures occurred. One propeller reconstruction showed distal superficial skin necrosis and one donor site wound dehisced; both were successfully managed conservatively. No other short-term or long-term complications occurred.

Flaps based on SPNAA perforators appear effective, reliable, and safe reconstructive methods for covering fibula osteocutaneous donor site defects and for intraoral reconstructions. Brequinar price Controlled trials are required to compare its effectiveness and safety with other reconstructive methods.

Flaps based on SPNAA perforators appear effective, reliable, and safe reconstructive methods for covering fibula osteocutaneous donor site defects and for intraoral reconstructions. Controlled trials are required to compare its effectiveness and safety with other reconstructive methods.