Development of mRNA manufacturing for vaccines and therapeutics: mRNA platform requirements and development of a scalable production process to support early phase clinical trials.

The remarkable success of SARS CoV-2 mRNA-based vaccines and the ensuing interest in mRNA vaccines and therapeutics have highlighted the need for a scalable clinical-enabling manufacturing process to produce such products, and robust analytical methods to demonstrate safety, potency, and purity. To date, production processes have either not been disclosed or are bench-scale in nature and cannot be readily adapted to clinical and commercial scale production. To address these needs, we have advanced an aqueous-based scalable process that is readily adaptable to GMP-compliant manufacturing, and developed the required analytical methods for product characterization, quality control release, and stability testing.

Quantitative Computed Tomography Assessment of Pectoralis and Erector Spinae Muscle Area and Disease Severity in Chronic Obstructive Pulmonary Disease Referred for Lung Volume Reduction.

Patients with advanced chronic obstructive pulmonary disease (COPD) develop skeletal muscle loss (sarcopenia) that is associated with adverse clinical outcomes including mortality. We evaluated if thoracic muscle area is associated with clinical outcomes in patients with severe COPD. We analyzed consecutive patients with severe COPD undergoing evaluation for lung volume reduction from 2015 to 2019 ( = 117) compared to current and former smoking controls undergoing lung cancer screening with normal lung function ( = 41).

Lower lobe lung volume reduction surgery: a case report.

Lung volume reduction surgery (LVRS) is an option for select patients with advanced chronic obstructive pulmonary disease (COPD). Current guidelines recommend LVRS for patients with appropriate physiology and heterogeneous distribution of emphysema predominately involving upper lobes. We present an unusual case of a 72-year-old male with an advanced COPD who suffered with recurrent exacerbations despite optimal medical management.

Rapamycin Reduced Ischemic Brain Damage in Diabetic Animals Is Associated with Suppressions of mTOR and ERK1/2 Signaling.

The objectives of the present study are to investigate the activation of mTOR and ERK1/2 signaling after cerebral ischemia in diabetic rats and to examine the neuroprotective effects of rapamycin. Ten minutes transient global cerebral ischemia was induced in straptozotocin-induced diabetic hyperglycemic rats and non-diabetic, euglycemic rats. Brain samples were harvested after 16 h of reperfusion.

Clinical characteristics and prediction of pulmonary hypertension in severe emphysema.

Background: We explored the prevalence, clinical and physiologic correlates of pulmonary hypertension (PH), and screening strategies in patients with severe emphysema evaluated for the National Emphysema Treatment Trial (NETT).

Methods: Patients undergoing Doppler echocardiography (DE) and right heart catheterization were included. Patients with mean pulmonary arterial pressure ≥ 25 mmHg (PH Group) were compared to the remainder (non-PH Group).

Multidisciplinary care of the patient with chronic obstructive pulmonary disease.

The National Emphysema Treatment Trial used a multidisciplinary team approach to implement the maximum medical care protocol, including adjustment of medications and outpatient pulmonary rehabilitation for all patients and nutritional and psychological counseling as needed. This article discusses the benefits of such an approach in the care of the patient with chronic obstructive pulmonary disease. Team member roles complement each other and contribute to the goal of providing the highest-quality medical care.

NETT coordinators: researchers, caregivers, or both?

The National Emphysema Treatment Trial (NETT) required the coordinated evaluation and treatment of thousands of patients with emphysema simultaneous with data collection to evaluate the safety and efficacy of surgery versus medical treatment for emphysema. These tasks were performed by a multidisciplinary team led by the clinic coordinator at each NETT center. The clinic coordinators functioned as members of the research team as well as communicators, managers, and members of the patient care team.

Bronchoscopic approach to COPD.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition that has frequent morbidity and mortality, with associated costs of US $ 2.5 billion annually and nearly 14,000 deaths each year. In the most advanced stages it causes debilitating breathlessness which is not improved despite maximal medical therapy including smoking cessation, bronchodilators, steroids and supplemental oxygen.

Lung volume reduction surgery in patients with emphysema and alpha-1 antitrypsin deficiency.

Background: The role of lung volume reduction surgery (LVRS) for individuals with alpha-1 antitrypsin (AAT) deficiency is unclear.

Methods: To assess the role of LVRS in individuals with severe deficiency of AAT, outcomes within the National Emphysema Treatment Trial were analyzed.

Results: Of 1218 randomized subjects, 16 (1.

Patient and surgical factors influencing air leak after lung volume reduction surgery: lessons learned from the National Emphysema Treatment Trial.

Background: Although staple line buttressing is advocated to reduce air leak after lung volume reduction surgery (LVRS), its effectiveness is unknown. We sought to identify risk factors for air leak and its duration and to estimate its medical consequences for selecting optimal perioperative technique(s), such as buttressing technique, to preempt or treat post-LVRS air leak.

Methods: Detailed air leak data were available for 552 of 580 patients receiving bilateral stapled LVRS in the National Emphysema Treatment Trial.

Role of flexible bronchoscopy in immunocompromised patients with lung infiltrates.

Study Objective: To study the diagnostic role of flexible bronchoscopy (FB) in immunocompromised patients with pulmonary infiltrates.

Design: Prospective, observational study.

Setting: Tertiary care hospital.